Liver Stereotactic Body Radiation Therapy Research Articles

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.

Liver stereotactic body radiation therapy without fiducial or retained ethiodized oil guidance warrants greater than 5 mm planning target volumes.

For liver stereotactic body radiation therapy (SBRT), the placement of fiducial markers or retained ethiodized oil by transarterial chemoembolisation (TACE) provides a landmark for consistent target localisation. TACE and fiducial markers are invasive procedures that harbour additional risks. We hypothesise that liver SBRT can be accurately delivered without the use of these invasive surrogate markers. We retrospectively identified 50 consecutive patients who underwent liver SBRT with respiratory motion management to a single lesion which exhibited retained ethiodized oil per prior TACE delivery. For each SBRT fraction, two manual rigid image registrations were performed by the treating physician. One using the liver contour as a surrogate for the target and second aligning only to the radio-opaque retained ethiodized oil of the treated lesion. The magnitude of the displacement vector between the two registration methods was used to assess the accuracy of target localisation if ethiodized oil was not present. For the 50 patients, a total of 244 analysable cone-beam CTs (CBCTs) were included (six CBCTs excluded due to poor ethiodized oil visualisation). Respiratory motion management techniques consisted of active breathing control for 13 and abdominal compression for 37 patients. Forty-two patients had peripheral lesions and eight had central lesions (<2 cm from left and right portal veins). The average target localisation offset between the two registration methods (i.e. liver contour vs. retained ethiodized oil alignment) for patients with a single peripheral or central liver lesion was 5.8 and 5.3 mm, respectively. Across all patients, the average change in target position exceeded 5 mm for image registration methods based on the liver contour alone versus the retained ethiodized oil region. This suggests that margins greater than 5 mm may be required for respiratory motion-managed liver SBRT treatments in patients who do not undergo prior TACE or fiducial placement.

Are liver contour and bone fusion comparable to fiducials for IGRT in liver SBRT?

Liver stereotactic body radiotherapy (SBRT) is increasingly being used to treat tumours. The purpose of this study was to compare the differences in patient positioning when using implanted fiducials as surrogates compared to alternative methods based on liver contour or bone registration. Eighteen patients treated with SBRT who underwent a fiducial placement procedure were included. Fiducial guidance was our gold standard to guide treatment in this study. After recording the displacements, when fusing the planning CT and CBCT performed in the treatment unit using fiducials, liver contour and bone reference, the differences between fiducials and liver contour and bone reference were calculated. Data from 88 CBCT were analyzed. The correlation between the displacements found with fiducials and those performed based on the liver contour and the nearest bone structure as references was determined. The mean, median, variance, range and standard deviation of the displacements with each of the fusion methods were obtained. μ, Ʃ, and σ values and margins were obtained. Lateral displacements of less than 3mm with respect to the gold standard in 92% vs. 62.5% of cases using liver contour and bone references, respectively, with 93.2% vs. 65.9% in the AP axis and SI movement in 69.3% vs. 51.1%. The errors μ, σ and Ʃ of the fusions with hepatic contour and bone reference in SI were 0.26mm, 4mm and 3mm, and 0.8mm, 5mm and 3mm respectively. Our study showed that displacements were smaller with the use of hepatic contour compared to bone reference and comparable to those obtained with the use of fiducials in the lateral, AP and SI motion axes. This would justify that hepatic contouring can be a guide in the treatment of patients in the absence of fiducials.

Dosimetric Comparison Study Between Free Breathing and Breath Hold Techniques in Patients Treated by Liver-Directed Stereotactic Body Radiation Therapy.

Background Breathing motion management is the key to delivering stereotactic body radiation therapy (SBRT) for liver lesions. This study aimed to compare the dosimetric parameters of liver SBRT using two different techniques: free breathing and breath hold. Method The study included 11 patients with liver metastases or hepatocellular carcinoma who underwent liver-directed SBRT. A dosimetric comparison was performed using dose-volume histogram analysis, evaluating parameters such as the maximum dose to 5 cc of bowel volume, mean liver dose (MLD), and liver V20and V30. Statistical analyses were performed to compare results. Results The findings revealed that the breath hold technique resulted in significantly lower doses to the bowel and smaller volumes of normal liver tissue receiving 20 Gy (V20) and 30 Gy (V30) than the free breathing. Although there was no statistically significant difference in the MLD between the two techniques, the breath hold technique resulted in a lower MLD. Conclusion This dosimetric comparison study suggests that the breath hold technique is associated with lower radiation exposure to the bowel and normal liver tissues. Although this may not be feasible for all patients, it may be an appropriate procedure for selected individuals. Further research is needed to validate these findings in different patient populations and explore their impact on clinical outcomes and patient-reported quality of life.

Online verification of breath-hold reproducibility using kV-triggered imaging for liver stereotactic body radiation therapy.

To introduce a new technique for online breath-hold verification for liver stereotactic body radiation therapy (SBRT) based on kilovoltage-triggered imaging and liver dome positions. Twenty-five liver SBRT patients treated with deep inspiration breath-hold were included in this IRB-approved study. 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 5 mm in the superior-inferior direction. If the liver dome 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 fell within boundaries. The liver dome was delineated on each triggered image. The mean distance between the delineated liver dome to the projected planning liver contour was defined as liver dome position error edome . The mean and maximum edome of each patient were compared between no breath-hold verification (all triggered images) and with online breath-hold verification (triggered images without beam-hold). Seven hundred thirteen breath-hold triggered images from 92 fractions were analyzed. For each patient, an average of 1.5 breath-holds (range 0-7 for all patients) resulted in beam-hold, accounting for 5% (0-18%) of all breath-holds; online breath-hold verification reduced the mean edome from 3.1 mm (1.3-6.1 mm) to 2.7 mm (1.2-5.2 mm) and the maximum edome from 8.6 mm (3.0-18.0 mm) to 6.7 mm (3.0-9.0 mm). The percentage of breath-holds with edome >5 mm was reduced from 15% (0-42%) without breath-hold verification to 11% (0-35%) with online breath-hold verification. online breath-hold verification eliminated breath-holds with edome >10 mm, which happened in 3% (0-17%) of all breath-holds. It is clinically feasible to monitor the reproducibility of each breath-hold during liver SBRT treatment using triggered images and liver dome. Online breath-hold verification improves the treatment accuracy for liver SBRT.

Long-Term Clinical Results of MR-Guided Stereotactic Body Radiotherapy of Liver Metastases.

(1) Background: Magnetic-resonance (MR)-guided stereotactic body radiotherapy (SBRT) allows for ablative, non-invasive treatment of liver metastases. However, long-term clinical outcome data are missing. (2) Methods: Patients received MR-guided SBRT with a MRIdian Linac between January 2019 and October 2021 and were part of an ongoing prospective observational registry. Local hepatic control (LHC), distant hepatic control (DHC), progression free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method. Toxicity was documented according to CTCAE (v.5.0). (3) Results: Forty patients were treated for a total of 54 liver metastases (56% with online plan adaptation). Median prescribed dose was 50 Gy in five fractions equal to a biologically effective dose (BED) (alpha/beta = 10 Gy) of 100 Gy. At 1 and 2 years, LHC was 98% and 75%, DHC was 34% and 15%, PFS was 21% and 5% and OS was 83% and 57%. Two-year LHC was higher in case of BED > 100 Gy (100% vs. 57%; log-rank p = 0.04). Acute grade 1 and 2 toxicity (mostly nausea) occurred in 26% and 7% of the patients, with no grade ≥ 3 event. (4) Conclusions: To our knowledge, this is the largest cohort of MR-guided liver SBRT. Long-term local control was promising and underscores the aim of achieving >100 Gy BED. Nonetheless, distant tumor control remains challenging.

Fiducial Markers Allow Accurate and Reproducible Delivery of Liver Stereotactic Body Radiation Therapy

Fiducial markers are utilized for image guided radiotherapy (IGRT) alignment during the delivery of liver stereotactic body radiosurgery (SBRT). There are limited data demonstrating the impact of matching fiducials on the accuracy of liver SBRT. This study quantifies the benefit of fiducial-based alignment and improvements in inter-observer reliability. Nineteen patients with 24 liver lesions were treated with SBRT. Target localization was performed using fiducial markers on cone-beam computed tomography (CBCT). Each CBCT procedure was retrospectively realigned to match both the liver edge and fiducial markers. The shifts were recorded by seven independent observers. Inter-observer variability was analyzed by calculating the mean error and uncertainty for the set-up. The mean absolute Cartesian error observed from fiducial and liver edge-based alignment was 1.5 mm and 5.3 mm, respectively. The mean uncertainty from fiducial and liver edge-based alignment was 1.8 mm and 4.5 mm, respectively. An error of 5 mm or greater was observed 50% of the time when aligning to the liver surface versus 5% of the time when aligning to fiducial markers. Aligning to the liver edge significantly increased the error, resulting in increased shifts when compared to alignment to fiducials. Tumors of 3 cm or farther from the liver dome had higher mean errors when aligned without fiducials (4.8 cm vs. 4.4 cm, p = 0.003). Our data support the use of fiducial markers for safer and more accurate liver SBRT.

Comprehensive Treatment Uncertainty Analysis and PTV Margin Estimation for Fiducial Tracking in Robotic Liver Stereotactic Body Radiation Therapy.

This study aims to quantify the uncertainties of CyberKnife Synchrony fiducial tracking for liver stereotactic body radiation therapy (SBRT) cases, and evaluate the required planning target volume (PTV) margins. A total of 11 liver tumor patients with a total of 57 fractions, who underwent SBRT with synchronous fiducial tracking, were enrolled for the present study. The correlation/prediction model error, geometric error, and beam targeting error were quantified to determine the patient-level and fraction-level individual composite treatment uncertainties. The composite uncertainties and multiple margin recipes were compared for scenarios with and without rotation correction during treatment. The correlation model error-related uncertainty was 4.3±1.8, 1.4±0.5 and 1.8±0.7 mm in the superior-inferior (SI), left-right, and anterior-posterior directions, respectively. These were the primary contributors among all uncertainty sources. The geometric error significantly increased for treatments without rotation correction. The fraction-level composite uncertainties had a long tail distribution. Furthermore, the generally used 5-mm isotropic margin covered all uncertainties in the left-right and anterior-posterior directions, and only 75% of uncertainties in the SI direction. In order to cover 90% of uncertainties in the SI direction, an 8-mm margin would be needed. For scenarios without rotation correction, additional safety margins should be added, especially in the superior-inferior and anterior-posterior directions. The present study revealed that the correlation model error contributes to most of the uncertainties in the results. Most patients/fractions can be covered by a 5-mm margin. Patients with large treatment uncertainties might need a patient-specific margin.

PO-1896 Dosimetric impact of tumour rotation in real-time adaptive liver stereotactic body radiation therapy

PO-1896 Dosimetric impact of tumour rotation in real-time adaptive liver stereotactic body radiation therapy

The Role of Stereotactic Body Radiation Therapy in the Management of Liver Metastases

The liver is a common site for metastatic spread for various primary tumor histologies. Stereotactic body radiation therapy (SBRT) is a non-invasive treatment technique with broad patient candidacy for the ablation of tumors in the liver and other organs. SBRT involves focused, high-dose radiation therapy delivered in one to several treatments, resulting in high rates of local control. Use of SBRT for ablation of oligometastatic disease has increased in recent years and emerging prospective data have demonstrated improvements in progression free and overall survival in some settings. When delivering SBRT to liver metastases, clinicians must balance the priorities of delivering ablative tumor dosing while respecting dose constraints to surrounding organs at risk (OARs). Motion management techniques are crucial for meeting dose constraints, ensuring low rates of toxicity, maintaining quality of life, and can allow for dose escalation. Advanced radiotherapy delivery approaches including proton therapy, robotic radiotherapy, and real-time MR-guided radiotherapy may further improve the accuracy of liver SBRT. In this article, we review the rationale for oligometastases ablation, the clinical outcomes with liver SBRT, tumor dose and OAR considerations, and evolving strategies to improve liver SBRT delivery.

Long-term characterization of MRI-morphologic alterations after active motion-compensated liver SBRT: a multi-institutional pooled analysis

BackgroundStereotactic body radiotherapy (SBRT) is an effective therapeutic approach in patients with liver metastases. However, long-term changes in hepatic normal tissue have to be taken into account in multimodal treatment regimes. Magnetic-resonance-imaging (MRI) based morphologic liver alterations (MMA) after liver SBRT have been analyzed longitudinally.Material and methods57 patients treated with gantry-based or robotic-based SBRT of 69 treatment volumes of liver metastases, who had long-term follow-up (FU) ≥6 months were included in this retrospective analysis. Post-SBRT MMAs were contoured on each contrast-enhanced-T1-weighted (T1w) MRI-sequence. Morphologic/volumetric data of the liver and MMAs were evaluated longitudinally, including the dependency on treatment-related factors of the planning target volume (PTV) and liver.ResultsThe median FU time was 1 year [6–48 months]. 66 of 69 treatment volumes developed MMAs (mean 143.8 ± 135.1 ccm at first appearance). 31.8% of MMAs resolved completely during FU. Of the persisting MMAs 82.2%/13.3% decreased/increased in size until last available FU. Morphological characterization of the MMAs at first appearance included 75% hypointense and 25% hyperintense T1w-MRI-based appearances. Hypointense as compared to hyperintense appearance was significantly associated with a higher mean liver dose EQD2α/β=3 Gy (p = 0.0212) and non-significantly greater MMA size. Variance analysis demonstrated a significant reduction of MMA and total liver volume after SBRT (p < 0.0001). The volume reduction decelerated longitudinally for both MMA (p < 0.0001) and liver size (p = 0.0033). Radiation doses (PTV-BEDα/β=3 Gy and 10 Gy) were not significantly associated with MMA volume reduction. SBRT of liver metastases with mean liver dose EQD2α/β=3 Gy > 18 Gy were characterized by greater MMA volumes (p = 0.0826) and steeper MMA reduction gradients during FU than those with EQD2α/β=3 Gy ≤ 18 Gy (p < 0.0001).ConclusionRadiogenic MMAs either completely resolve or usually decrease in volume with pronounced reduction during short-term FU. This course was independent of the MMA’s morphological appearance. Further, increased mean liver dose was associated with greater MMA size and a greater gradient of MMA size reduction during FU.

Refining stereotactic body radiation therapy as a bridge to transplantation for hepatocellular carcinoma: An institutional experience.

Stereotactic body radiotherapy (SBRT) has been established as a safe and effective treatment for hepatocellular carcinoma (HCC). Currently, there are no consensus guidelines to advise optimal patient selection and radiotherapy planning parameters to minimise the risk of surgical and medical complications after liver transplant (LT) in patients who have had prior SBRT for HCC, whilst optimising treatment benefit. We performed a retrospective analysis of all adult patients who received liver SBRT as a bridge to LT at a tertiary institution between 2017 and 2019. Nine patients received SBRT as bridging therapy to LT. HCC location varied from peripheral to central/hilar regions and HCC diameter was 13-54 mm. Median time between SBRT and LT was 141 days (range 27-461 days). Median operating time was 360 min (range 270-480 min). Four patients (44%) had visible SBRT reaction or fibrosis at the time of LT. SBRT reaction resulted in clinical impact in one patient (11%) only, where vascular clamping of the IVC was required for 10 min. SBRT is a safe and effective treatment for HCC enabling patients to remain within LT criteria, even for lesions not amenable to other more conventional bridging therapies. We describe a preliminary decision pathway to guide the optimal use of SBRT as a bridge to LT developed in our institution.

Stereotactic MR-Guided Radiotherapy for Liver Metastases: First Results of the Montpellier Prospective Registry Study.

Liver stereotactic body radiotherapy (SBRT) is a local treatment that provides good local control and low toxicity. We present the first clinical results from our prospective registry of stereotactic MR-guided radiotherapy (MRgRT) for liver metastases. All patients treated for liver metastases were included in this prospective registry study. Stereotactic MRgRT indication was confirmed by multidisciplinary specialized tumor boards. The primary endpoints were acute and late toxicities. The secondary endpoints were survival outcomes (local control, overall survival (OS), disease-free survival, intrahepatic relapse-free survival). Twenty-six consecutive patients were treated for thirty-one liver metastases between October 2019 and April 2022. The median prescribed dose was 50 Gy (40-60) in 5 fractions. No severe acute MRgRT-related toxicity was noted. Acute and late gastrointestinal and liver toxicities were low and mostly unrelated to MRgRT. Only 5 lesions (16.1%) required daily adaptation because of the proximity of organs at risk (OAR). With a median follow-up time of 17.3 months since MRgRT completion, the median OS, 1-year OS and 2-year OS rates were 21.7 months, 83.1% (95% CI: 55.3-94.4%) and 41.6% (95% CI: 13.5-68.1%), respectively, from MRgRT completion. The local control at 6 months, 1 year and 2 years was 90.9% (95% CI: 68.3-97.7%). To our knowledge, we report the largest series of stereotactic MRgRT for liver metastases. The treatment was well-tolerated and achieved a high LC rate. Distant relapse remains a challenge in this population.