Liver Stereotactic Body Radiation Therapy Research Articles

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

A portable respiratory training system with a gyroscope sensor (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 liver stereotactic body 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 2.1%. Among volunteers, the mean percentages of errors within ±15% of the respiratory waveforms acquired by the GRTS and RGSC were 95.5% for free breathing and 80.7% 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 liver stereotactic body radiation therapy. A respiratory training system with a gyroscope sensor is inexpensive and portabl, 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.

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.

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.

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.

Cardiac migration of an implanted hepatic fiducial marker used for stereotactic body radiation therapy - A case report.

Stereotactic body radiation therapy (SBRT) has been increasingly used to treat liver malignancies because large doses of radiation can be delivered precisely to the target with a rapid dose falloff. Real-time tracking of implanted fiducial markers (FMs), combined with respiratory gating, further improves the accuracy of treatment delivery and reduces the dose to critical structures. There have been reports of migration of the FMs after implantation for SBRT. Calypso beacons, which use the electromagnetic wave reflections for the image guidance, have recently been used for image-guided liver SBRT. In the literature, there are no reports on the migration of Calypso beacons to the heart after implantation in the liver. In this report, we detail the first case of such migration. Respiratory-gated SBRT guided by the Calypso system was planned for our patient, who developed liver metastases in segments 6 and 5/4B shortly after the completion of radical chemoradiotherapy for anal squamous cell carcinoma. One of the three Calypso beacons inserted in the liver under computed tomography (CT) guidance was found to have migrated to the right ventricle, as seen in CT simulation images. SBRT was delivered with respiratory gating using the remaining two beacons. A fluoroscopic imaging performed during treatment confirmed the migrated marker to the right ventricle. Patient denied any cardiac symptoms and SBRT were delivered uneventfully. Ten months later, the patient died of disease progression.

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.

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.

Clinical and Dosimetric Impact of 2D kV Motion Monitoring and Intervention in Liver Stereotactic Body Radiation Therapy

PurposePositional errors resulting from motion are a principal challenge across all disease sites in radiation therapy. This is particularly pertinent when treating lesions in the liver with stereotactic body radiation therapy (SBRT). To achieve dose escalation and margin reduction for liver SBRT, kV real-time imaging interventions may serve as a potential solution. In this study, we report results of a retrospective cohort of liver patients treated using real-time 2D kV-image guidance SBRT with emphasis on the effect of (1) clinical workflow, (2) treatment accuracy, and (3) tumor dose. Methods and MaterialsData from 33 patients treated with 41 courses of liver SBRT were analyzed. During treatment, planar kV images orthogonal to the treatment beam were acquired to determine treatment interventions, namely treatment pauses (ie, adequacy of gating thresholds) or treatment shifts. Patients were shifted if internal markers were >3 mm, corresponding to the PTV margin used, from the expected reference condition. The frequency, duration, and nature of treatment interventions (ie, pause vs shift) were recorded, and the dosimetric effect associated with treatment shifts was estimated using a machine learning dosimetric model. ResultsOf all fractions delivered, 39% required intervention, which took on average 1.9 ± 1.6 minutes and occurred more frequently in treatments lasting longer than 7 minutes. The median realignment shift was 5.7 mm in size, and the effect of these shifts on minimum tumor dose in simulated clinical scenarios ranged from 0% to 50% of prescription dose per fraction. ConclusionReal-time kV-based imaging interventions for liver SBRT minimally affect clinical workflow and dosimetrically benefit patients. This potential solution for addressing positional errors from motion addresses concerns about target accuracy and may enable safe dose escalation and margin reduction in the context of liver SBRT.

Feasibility and tolerability of breath-hold in liver stereotactic body radiotherapy with surface guided radiotherapy

PurposeIntrafractional motion constitutes a significant challenge in SBRT (Stereotactic Body Radiotherapy).The breath-hold (BH) technique is employed to mitigate tumor motion; however, ensuring reproducibility and consistency remains critically important. Surface tracking systems, integrated into the treatment process, facilitate motion tracking through three-dimensional camera technology. Surface guidance has been incorporated with Varian EDGE (Varian Medical Systems, Palo Alto, CA, USA) and has been utilized at multiple treatment sites within our department since 2018. Drawing on four years of experience, this study aims to publish patient experience, assess the feasibility, and evaluate the tolerability of breath-hold during SBRT with surface guided radiotherapy (SGRT), particularly focusing on a specific subgroup: patients with liver metastases. MethodsProspective evaluation was conducted on patients with liver metastases undergoing breath-hold SBRT with SGRT. A two-step survey consisting of seven questions was administered after CT simulation and treatment. Treatment duration and the number of breath-holds were recorded. Additionally, factors potentially influencing SGRT and treatment time were assessed. ResultsBetween April 2021 and May 2022, a total of 41 patients underwent 171 fractions of treatment. According to the questionnaire, prior training was found to be beneficial, and breath-holding during the procedure was tolerable. Patients reported experiencing slight stress due to their active participation in the treatment. Factors such as Karnofsky Performance Status (KPS), age, lung volume, conditions affecting lung capacity, previous breath-hold history, and being a native speaker showed no correlation with treatment time. Moreover, these factors did not correlate with the tolerability of breath-hold during SGRT. However, female patients showed better breath-holding performance in SGRT treatments compared to male patients (p: 0.02). ConclusionsThe application of breath-hold with SGRT procedures is tolerable and feasible in liver SBRT treatments. There exists no specific subgroup that cannot tolerate this method.

Assessment of Daily Target Motion to Optimize ITV Margins in Online Adaptive Plan for Liver and Pancreatic SBRT on MR-LINAC

Accurate measurement of daily target motion on online plan adaptation is essential for re-optimizing the internal target volume (ITV) margins. In this study, by analyzing 2D cine MR images acquired in a 1.5T MR-Linac, we assessed daily target motion and its inter-fractional variations, which is then used to customize ITV margins for MR-based online adaptive plan of liver and pancreatic stereotactic body radiotherapy (SBRT). Twenty-threepatients, enrolled in this study, underwent MR-guided online adaptive SBRT on 1.5 T MR-Linac: liver (n = 12 without compression belt (CB), n = 2 with CB) and pancreas (n = 9 with CB). Target motion in a 2D coronal and sagittal MR images (> 200 cine images to cover multiple breathing cycles), as well as a set of 4D-CT images during the simulation, was analyzed to determine patient specific ITV margins for a reference plan. On every fraction of online adaptive SBRT, the 2D MR images were exported to commercially available software along with a planning MR images: a T1-wighted MR image set for pancreas and or a navigated T2-wighted MR image set for liver. Daily target motion was then measured by overlaying the orthogonal cine image set on the T1- or T2-wighted image set. The ITV margin was adjusted when required prior to online plan optimization RESULTS: Thisstudy successfully assessed the daily target motion and inter-fractional variations in 23 liver or pancreatic cancer patients. We found a discrepancy of daily target motion of orthogonal 2D cine MR images from that of 4D-CT, required to adjust the ITV margin for online plan adaptation. In liver SBRT without CB, 15 out of 45 fractions from 12 patients (33.3 %) went through adjusted ITV margin. The tumor motion was large up to a 2.2 cm along the inferior direction in a patient without CB and thus the patient was treated on a conventional Linac with the active breathing control (ABC) unit for breath-hold. On the other hand, no adjustments were necessary for 2 liver patients with CB. In 9 patients with pancreatic cancers, we found the inter-fractional ITV variations in 3 out of 45 fractions (6.7 %) adjusted the ITV margin. The daily target motion in the pancreatic patients with CB was more stable and relatively smaller than that of the liver patients. Theorthogonal 2D cine MR images are evidently essential for assessing daily target motion to evaluate the inter-fractional variation and achieve daily ITV-customized liver and pancreatic SBRT in the 1.5 T MR-Linac. The customized ITV approach will improve the treatment outcome of the MR-guided online adaptive therapy.

Racial Disparities in the Utilization of Stereotactic Body Radiation Therapy (SBRT) in Patients with Hepatocellular Carcinoma

SBRT has now been demonstrated to improve OS, PFS and TTP in patient with hepatocellular carcinoma (HCC) when compared to systemic therapy alone. Disparities in the availability and utilization of SBRT for minority racial patients may affect oncologic outcomes. This study examines racial and sociodemographic disparities in the utilization of SBRT for HCC patients. In this registry-based cohort study, data from the American College of Surgeons National Cancer Database (NCDB) from 2004 - 2017 was analyzed. Adults with a new diagnosis of localized, non-metastatic, HCC were included in this analysis. Patients were sub-grouped by race and whether they were treated with liver SBRT. In this analysis, SBRT was defined as radiation delivered in 3-5 fractions and in the 30-60Gy range. The primary outcome of this study was the utilization rate of liver SBRT in HCC, depending on race. Survival was also examined in these patients. Statistical analysis was performed using SPSS v28 for univariate and multivariate logistical regression and Kaplan-Meier analysis. From 2004 - 2017, 95132 cases of localized HCC were identified in patients who were white, non-Spanish, non-Hispanic (WNH) and 40964 cases who were black or Hispanic/Spanish (BH). Of all these patients, only 1963 patients, or 1.4%, were treated with liver SBRT. Comparing WNH patients to BH patients, 1423 (1.5%) WNH patients were treated with SBRT and 334 (0.8%) BH patients were treated with SBRT (p<0.001). Looking at the number of patients treated with SBRT each year, there has been a yearly increase in the use of liver SBRT, from 48 patients in 2007 to 340 patients in 2017. The utilization of SBRT in WNH patients has increased at a higher rate than for BH patients over this time period. The median survival for patients with localized HCC was similar for both WNH and BH patients with a median survival of 17 months (p = 0.36). However, patients who were treated with liver SBRT had an improved median survival of 25 months for WNH patients and 34 months for BH patients (p<0.001). Overall, liver SBRT is severely underutilized for patients with localized HCC in the patient population represented in this database, and fewer BH patients are treated with liver SBRT compared with WNH patients. Liver SBRT is associated with improved survival of HCC patients in this study. With the findings of the RTOG 1112 trial, demonstrating improved OS and PFS with the use of SBRT for HCC, it is essential to adopt liver SBRT more broadly and to develop strategies to reduce the racial disparities in utilization.

Using kV Triggered Imaging and Liver Dome Position to Reduce the Dosimetric Error Caused by Breath Hold Variability for Liver Stereotactic Body Radiation Therapy

In a previous study, we demonstrated that manual gating using kV triggered imaging and liver dome position can reduce targeting errors caused by breath hold variability for liver stereotactic body radiation therapy (SBRT). In this study, we quantified the dosimetric error caused by breath hold variability and investigated the effect of liver dome gating on reducing dosimetric error. Twenty-five liver SBRT patients treated with deep inspiration breath-hold were included in this IRB approved study. Volumetric modulated arc therapy was used to deliver 30-60 Gy in 1-5 fractions. To verify the breath-hold reproducibility during treatment, a KV triggered image was acquired at the beginning of each breath-hold. The liver dome position was visually compared with the expected upper/lower liver boundaries created by expanding/contracting the liver contour 5mm in the superior-inferior direction. If the liver dome position was within the boundaries, delivery continued; otherwise, beam was held manually and the patient was instructed to take another breath hold until the liver dome position was within boundaries. To calculate delivered dose, for each fraction, the treatment plan was divided into sub-beams, each corresponding to one breath hold using delivery log files. The triggered images were registered to the planning CT to determine the liver position during each breath hold. Dose delivered during each breath hold was calculated by shifting the isocenter of the sub-beam according to the liver position. Breath holds discarded by gating were excluded since no dose was delivered during these breath holds. Delivered fractional doses were compared with planned fractional doses using GTV D99 and liver Dmean. To estimate delivered dose without gating, the first "corrective" breath hold taken after the discarded breath holds was replaced with the prior discarded breath hold and dose calculation was repeated. Seven hundred eleven triggered images from 91 treatment fractions were analyzed. Without gating, in 11 of the 91 fractions from 7 of the 25 patients, delivered GTV D99 reduced > 0.50 Gy from planned value (range 0.51-1.68 Gy, 3-10% of planned fractional GTV D99). Liver dome gating was able to detect/exclude irreproducible breath holds in 8 of the 11 fractions, increasing the delivered GTV D99 by 0.70 Gy per fraction on average (range 0.21-1.63 Gy). With liver dome gating, delivered fractional GTV D99 was comparable to planned value for all fractions (12.96 +/- 5.19 Gy vs 13.04 +/- 5.18 Gy, p > 0.05). Liver mean dose was not affected by breath hold variability or gating. Fractional liver Dmean was 2.26 +/- 1.19 Gy from plan, 2.27 +/- 1.21 Gy for delivery with gating and 2.27 +/- 1.20 Gy for delivery without gating. Breath hold variability may cause tumor underdose. Liver dome gating using kV triggered imaging reduces dosimetric error and ensures tumor coverage for liver SBRT.

Liver Stereotactic Body Radiation Therapy (SBRT) to Downstage Patients with Hepatocellular Carcinoma prior to Liver Transplant

Orthotopic liver transplantation (OLT) marks the most successful treatment for hepatocellular carcinoma (HCC) patients meeting Milan criteria. The process of reducing the disease burden of HCC patients not currently meeting criteria for OLT with local therapy is referred to as "downstaging" and has proven to be a feasible approach. RTOG 1112 recently demonstrated the efficacy and acceptable toxicity of liver SBRT for treating HCC. However, limited data currently exists describing the efficacy of SBRT for downstaging HCC patients and facilitating OLT. A single institution IRB approved prospective liver SBRT registry was surveyed for all patients outside of Milan criteria (1 lesion >5 cm; 2-3 lesions >3 cm) without vascular invasion or extrahepatic disease. Patients felt least likely to become OLT candidates with downstaging (age >80, >4 lesions, lesion >12 cm) were excluded. The primary endpoints were downstaging and OLT. Secondary endpoints were time to transplant, local control (LC), recurrence free survival (RFS) and overall survival (OS). A total of 38 HCC patients with a median age of 65 years (range 28 - 80) met inclusion criteria. Median follow up was 14 months (IQR 3 - 35). At baseline, median KPS was 80 (range 60 - 100) with 16 Child-Pugh (CP) A (42%), 13 CP B (34%), and 9 CP C patients (24%). All patients were outside of Milan criteria and 25 patients (66%) were outside of UCSF criteria at time of SBRT. No patients had extrahepatic disease or vascular invasion. Median number of lesions, largest tumor size, and total sum of lesions were 2 (range 1 - 4), 5.0 cm (IQR, 4.0 - 6.5), and 6.6 cm (IQR 5.9 - 9.2), respectively. Prior to SBRT, 22 patients (58%) had received non-SBRT local therapy. At time of SBRT a variety of dose fractionation schedules were selected with a median BED10 of 78 (IQR 62 - 100). Concurrent sorafenib was used in 2 patients (8%). Following completion of SBRT, 21 patients (55%) were successfully downstaged at a median 3.0 months (IQR 1.9 - 6.1) after treatment, most frequently secondary to decrease in size of the largest lesion (86%). Twelve patients (32%) proceeded to undergo OLT at a median 7 months (IQR 3 - 14) after SBRT and 105 days (IQR 18 - 344) following successful downstaging. Of the 25 patients initially exceeding UCSF criteria, 7 (28%) underwent OLT. Among those receiving OLT, 5 patients (42%) remain alive without evidence of disease, 3 patients (25%) have recurred, 3 patients (33%) died within 2 years from transplant complications, and 1 patient (8%) died from an unrelated cause. LC at 2 years was 83%. Median RFS and OS for the overall cohort were 7 months (95% CI 0 - 21) and 24 months (95% CI 11 - 36), respectively. Among the transplant recipients, the median OS was 37 months (95% CI 30 - 44) compared to 15 months (95% CI 6 - 23) among those not receiving transplant. With careful patient selection, liver SBRT serves as a feasible downstaging method to facilitate OLT in HCC patients.

Evaluation of Liver Functionality after Liver Stereotactic Body Radiation Therapy (SBRT) Using Blood Tests and Imaging Examinations

Several studies have shown that liver function can be evaluated after hepatic stereotactic body radiation therapy (SBRT) using galactosyl human serum albumin (GSA) liver scintigraphy and Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI). However, there are no reports investigating the relationship (including Chile-Pugh classification) between imaging and blood tests. Therefore, we investigated the changes that occur in the liver between before and after SBRT by combining imaging (GSA, computed tomography (CT), and MRI) with blood tests that assess total liver function (albumin-bilirubin (ALBI) grade, ICG-R15). We decided to find a method that could assess liver reserve capacity locally and globally MATERIALS/METHODS: Of the 23 patients who underwent hepatic SBRT, 12 patients underwent GSA, MRI, and ICG-R15 testing before treatment, 1 month after treatment, and 3 months after treatment. All patients underwent imaging studies and blood tests at the beginning of treatment, 1 month after treatment, and 3 months after treatment ended. The evaluation items were as follows: 1) changes over time in Child-Pugh classification, ICG-R15, and ALBI values before and after SBRT; 2) changes over time in GSA count and ICG; and 3) selection of the optimal sequence for recognizing radiation hepatitis on MRI. The ICG values were 14.4 before RT, 17.1 after 1 month, and 17.6 after 3 months. ICG worsened after 1 month of treatment, but was similar after 3 months. ALBI values were -2.61 before RT, -2.67 after 1 month, and -2.71 after 3 months. ALBl worsened slightly over time. Regarding the ICG-R15, there was an average worsening of 2.8 after 1 month of treatment compared with before SBRT, but only of 0.5 between 1 month and 3 months after SBRT. Therefore, evaluation using ICG-R15 after SBRT after 1 month alone may be sufficient.

Pre-Treatment Trends in Child-Pugh Score as an Indicator of Post-Treatment Survival in Patients Receiving Liver SBRT for HCC

We sought to understand the value of Child-Pugh (CP) score trends prior to undergoing stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma in patients with advanced cirrhosis, as an indicator of post-treatment morbidity and mortality. We hypothesize that an uptrend in CP score prior to RT increases risk of post-treatment cirrhosis progression, or death. We retrospectively reviewed all patients who underwent definitive SBRT for HCC between 2014-2022 in our health system. Most patients were referred for treatment in the 2nd or 3rd line setting, allowing us to determine CP score at multiple points before SBRT. Response to treatment was evaluated with RECIST or mRECIST criteria. Acute treatment toxicities were assessed by CTCAE v5. OS was assessed using the Kaplan-Meier method, and differences between groups were evaluated using log-rank test. A total of 61 patients were identified, 26 had an immediate pre-SBRT CP score of A5, 11 with A6, 10 with B7, 4 with B8, 4 with B9, 5 with C10, and 1 with C11. Median prescribed dose was 40Gy in 5fx. Median OS of all patients was 24 months. When stratified by CP category, median OS for CP A was not reached (NR) at time of analysis, CP B had a median OS of 14.8mo, and CP C with 1.9mo (p < 0.01). Local control rate at 6mo was 87.5%. 5 patients (8.3%) had CTCAE grade 2 acute toxicity. 10 patients had CP score progression of 2pts or more within 6mo after treatment, and 7 patients had a cause of death attributed to end stage liver disease. Median time interval between HCC diagnosis and start of RT was 338 days. In this time interval, patients with a CP score increase of 2 pts or more prior to starting RT had a median OS of 362 days, compared to NR for patients without increase (p = 0.02). When excluding the CP A group, patients with 2 pt increase had median OS of 362 days vs 445 days (p = 0.34). Again excluding the CP A group, patients with a 1 pt increase had median OS of 362 days vs NR (p = 0.23). Of 9 patients who had a pre-RT CP score increase of 2 pts or more, 7 experienced continued CP progression after treatment. In this multi-institutional retrospective analysis, we found 24 patients with advanced CP B/C cirrhosis who underwent SBRT, none of whom received orthotopic liver transplant. While CP C patients did relatively poorly, we find that some patients with CP B cirrhosis may tolerate SBRT well with good oncologic effect. When taking pre-treatment CP score increase into consideration, we saw a trend but no statistical significance indicating that a pre-SBRT increase in CP score may be associated with worse OS after treatment among CP B/C patients. We conclude that there may be a subset of patients with advanced cirrhosis who, if well selected, are appropriate candidates for SBRT. We suggest a novel use of the CP score and pre-RT trends as an additional clinical tool to aid in decision making when selecting patients. We also suggest that patients with marked up-trending scores pre-treatment have a high likelihood of continued cirrhosis progression after treatment.

Study on the Clinical Use of a Respiratory Navigator Combined with Breath-Hold for MRI- Guided Liver SBRT

Respiratory movement strongly affects the accuracy of stereotactic body radiation therapy (SBRT) of liver malignancies treated without the use of a respiratory gating system. This study investigates the feasibility and advantages of using a respiratory navigator-guided combined with patient breath-hold for liver SBRT in an adaptive magnetic-resonance guided workflow. Clinical datasets of 10 liver cancer patients treated with 1.5T MR-Linac with respiratory navigator-guided SBRT combined with patient breath-hold were retrospectively analyzed. All patients underwent simulation CT with and without contrast, and 4D-CT and 3D-T2w MRI without contrast. Patients received a prescription dose ranging from 36 to 50 Gy in 5 to 8 fractions and followed the adapt to shape (ATS) workflow including contours adjustment and a subsequent MR-based synthetic CT (sCT) calculation on the online MRI acquired. The reference treatment plan was optimized on the expiratory phase of the 4D-CT, and during the online session the contours and the adapted plans were performed using the 3D-T2w navigator MRI of the patient's end-expiratory signal; 2D-T2w real-time monitoring MRI was also used as support for the contour's definition. The radiation therapist instructed the patients to hold their breath at the end of the breathing cycle for the time of the beam on. A total of 59 fractions were analyzed. For each fraction the dosimetric parameters of the target and normal liver of the adaptive and reference plans were compared; particularly the volume, the conformity index (CI) and gradient index (GI) for the target, and V5, V10 and Dmean for the normal liver. T-student statistical analysis was performed; a p-value less than 0.05 was considered statistically significant. In the free breathing state, the 3D-T2w navigator MRI images enable a clear visualization of the tumor and its boundaries. The average target CI of the adaptive and reference plans is not significantly different (p = 0.448), while the GI is significantly higher (p = 0.043). Normal liver V10 and Dmean are lower and V5 is slightly increased, but without statistical differences. The mean values and standard deviation of the dosimetric parameters of the reference and adapted plans are shown in the Table below. The use of a respiratory navigator combined with the breath-hold for MRI- guided liver SBRT allows clear visualization of the tumor, ensures the accuracy of the delivered dose and may be considered an alternative when the respiratory gating system is not available during MRgART sessions.