Quantification of the geometric uncertainty when using implanted markers as a surrogate for lung tumor motion.

BACKGROUND: Fiducial markers are used as surrogates for tumor location during radiation therapy treatment. Developments in lung fiducial marker and implantation technology have provided a means to insert markers endobronchially for tracking of lung tumors. This study quantifies the surrogacy uncertainty (SU) when using endobronchially implanted markers as a surrogate for lung tumor position. METHODS: We evaluated SU for 17 patients treated in a prospective electromagnetic-guided MLC tracking trial. Tumor and markers were segmented on all phases of treatment planning 4DCTs and all frames of pretreatment kilovoltage fluoroscopy acquired from lateral and frontal views. The difference in tumor and marker position relative to end-exhale position was calculated as the SU for both imaging methods and the distributions of uncertainties analyzed. RESULTS: The mean (range) tumor motion amplitude in the 4DCT scan was 5.9 mm (1.7-11.7 mm) in the superior-inferior (SI) direction, 2.2 mm (0.9-5.5 mm) in the left-right (LR) direction, and 3.9 mm (1.2-12.9 mm) in the anterior-posterior (AP) direction. Population-based analysis indicated symmetric SU centered close to 0 mm, with maximum 5th/95th percentile values over all axes of -2.0 mm/2.1 mm with 4DCT, and -2.3/1.3 mm for fluoroscopy. There was poor correlation between the SU measured with 4DCT and that measured with fluoroscopy on a per-patient basis. We observed increasing SU with increasing surrogate motion. Based on fluoroscopy analysis, the mean (95% CI) SU was 5% (2%-8%) of the motion magnitude in the SI direction, 16% (6%-26%) of the motion magnitude in the LR direction, and 33% (23%-42%) of the motion magnitude in the AP direction. There was no dependence of SU on marker distance from the tumor. CONCLUSION: We have quantified SU due to use of implanted markers as surrogates for lung tumor motion. Population 95th percentile range are up to 2.3 mm, indicating the approximate contribution of SU to total geometric uncertainty. SU was relatively small compared with the SI motion, but substantial compared with LR and AP motion. Due to uncertainty in estimations of patient-specific SU, it is recommended that population-based margins are used to account for this component of the total geometric uncertainty.

MLC tracking for lung SABR is feasible, efficient and delivers high-precision target dose and lower normal tissue dose.

BACKGROUND AND PURPOSE: The purpose of this work is to present the clinical experience from the first-in-human trial of real-time tumor targeting via MLC tracking for stereotactic ablative body radiotherapy (SABR) of lung lesions. METHODS AND MATERIALS: Seventeen patients with stage 1 non-small cell lung cancer (NSCLC) or lung metastases were included in a study of electromagnetic transponder-guided MLC tracking for SABR (NCT02514512). Patients had electromagnetic transponders inserted near the tumor. An MLC tracking SABR plan was generated with planning target volume (PTV) expanded 5 mm from the end-exhale gross tumor volume (GTV). A clinically approved comparator plan was generated with PTV expanded 5 mm from a 4DCT-derived internal target volume (ITV). Treatment was delivered using a standard linear accelerator to continuously adapt the MLC based on transponder motion. Treated volumes and reconstructed delivered dose were compared between MLC tracking and comparator ITV-based treatment. RESULTS: All seventeen patients were successfully treated with MLC tracking (70 successful fractions). MLC tracking treatment delivery time averaged 8 minutes. The time from the start of CBCT to the end of treatment averaged 22 minutes. The MLC tracking PTV for 16/17 patients was smaller than the ITV-based PTV (range -1.6% to 44% reduction, or -0.6 to 18 cc). Reductions in mean lung dose (27 cGy) and V20Gy (50 cc) were statistically significant (p < 0.02). Reconstruction of treatment doses confirmed a statistically significant improvement in delivered GTV D98% (p < 0.05) from planned dose compared with the ITV-based plans. CONCLUSION: The first treatments with lung MLC tracking have been successfully performed in seventeen SABR patients. MLC tracking for lung SABR is feasible, efficient and delivers high-precision target dose and lower normal tissue dose.

Geometric uncertainty analysis of MLC tracking for lung SABR.

PURPOSE: The purpose of this work was to report on the geometric uncertainty for patients treated with multi-leaf collimator (MLC) tracking for lung SABR to verify the accuracy of the system. METHODS: Seventeen patients were treated as part of the MLC tracking for lung SABR clinical trial using electromagnetic beacons implanted around the tumor acting as a surrogate for target motion. Sources of uncertainties evaluated in the study included the surrogate-target positional uncertainty, the beam-surrogate tracking uncertainty, the surrogate localization uncertainty, and the target delineation uncertainty. Probability density functions (PDFs) for each source of uncertainty were constructed for the cohort and each patient. The total PDFs was computed using a convolution approach. The 95% confidence interval (CI) was used to quantify these uncertainties. RESULTS: For the cohort, the surrogate-target positional uncertainty 95% CIs were ±2.5 mm (-2.0/3.0 mm) in left-right (LR), ±3.0 mm (-1.6/4.5 mm) in superior-inferior (SI) and ±2.0 mm (-1.8/2.1 mm) in anterior-posterior (AP). The beam-surrogate tracking uncertainty 95% CIs were ±2.1 mm (-2.1/2.1 mm) in LR, ±2.8 mm (-2.8/2.7 mm) in SI and ±2.1 mm (-2.1/2.0 mm) in AP directions. The surrogate localization uncertainty minimally impacted the total PDF with a width of ±0.6 mm. The target delineation uncertainty distribution 95% CIs were ±5.4 mm. For the total PDF, the 95% CIs were ±5.9 mm (-5.8/6.0 mm) in LR, ±6.7 mm (-5.8/7.5 mm) in SI and ±6.0 mm (-5.5/6.5 mm) in AP. CONCLUSION: This work reports the geometric uncertainty of MLC tracking for lung SABR by accounting for the main sources of uncertainties that occurred during treatment. The overall geometric uncertainty is within ±6.0 mm in LR and AP directions and ±6.7 mm in SI. The dominant uncertainty was the target delineation uncertainty. This geometric analysis helps put into context the range of uncertainties that may be expected during MLC tracking for lung SABR (ClinicalTrials.gov registration number: NCT02514512).

An augmented correlation framework for the estimation of tumour translational and rotational motion during external beam radiotherapy treatments using intermittent monoscopic x-ray imaging and an external respiratory signal.

Increasing evidence shows that intrafraction tumour motion monitoring must include both six degrees of freedom (6DoF): 3D translations and 3D rotations. Existing real-time algorithms for 6DoF target motion estimation require continuous intrafraction fluoroscopic imaging at high frequency, thereby exposing patients to additional high imaging dose. This paper presents the first method capable of 6DoF motion monitoring using intermittent 2D kV imaging and a continuous external respiratory signal. Our approach is to optimise a state-augmented linear correlation model between an external signal and internal 6DoF motion. In standard treatments, the model can be built using information obtained during pre-treatment cone beam CT (CBCT). Real-time 6DoF tumor motion can then be estimated using just the external signal. Intermittent intrafraction kV images are used to update the model parameters, accounting for changes in correlation and baseline shifts. The method was evaluated in silico using data from 6 lung SABR patients, with the internal tumour motion recorded with electromagnetic beacons and the external signal from a bellows belt. Projection images from CBCT (10 Hz) and intermittent kV images were simulated by projecting the 3D Calypso beacon positions onto an imager. IMRT and VMAT treatments were simulated with increasing imaging update intervals: 0.1 s, 1 s, 3 s, 10 s and 30 s. For all the tested clinical scenarios, translational motion estimates with our method had sub-mm accuracy (mean) and precision (standard deviation) while rotational motion estimates were accurate to <[Formula: see text] and precise to [Formula: see text]. Motion estimation errors increased as the imaging update interval increased. With the largest imaging update interval (30 s), the errors were [Formula: see text] mm, [Formula: see text] mm and [Formula: see text] mm for translation in the left-right, superior-inferior and anterior-posterior directions, respectively, and [Formula: see text], [Formula: see text] and [Formula: see text] for rotation around the aforementioned axes for both VMAT and IMRT treatments. In conclusion, we developed and evaluated a novel method for highly accurate real-time 6DoF motion monitoring on a standard linear accelerator without requiring continuous kV imaging. The proposed method achieved sub-mm and sub-degree accuracy on a lung cancer patient dataset.

4-Dimensional Cone Beam Computed Tomography-Measured Target Motion Underrepresents Actual Motion.

PURPOSE: Four-dimensional cone beam computed tomography (4DCBCT) facilitates verification of lung tumor motion before each treatment fraction and enables accurate patient setup in lung stereotactic ablative body radiation therapy. This work aims to quantify the real-time motion represented in 4DCBCT, depending on the reconstruction algorithm and the respiratory signal utilized for reconstruction. METHODS AND MATERIALS: Eight lung cancer patients were implanted with electromagnetic Calypso beacons in airways close to the tumor, enabling real-time motion measurements. 4DCBCT scans were reconstructed from projections for treatment setup CBCT for 1 to 2 fractions of 8 patients with the Feldkamp-Davis-Kress (FDK) algorithm or the prior image constrained compressed sensing (PICCS) method and internal real-time Calypso beacon trajectories or an external respiratory signal (bellows belt). The real-time beacon centroid ("target") motion was compared with beacon centroid positions segmented in the 4DCBCT reconstructions. We tested the hypotheses that (1) the actual target motion was accurately represented in the reconstructions and (2) the reconstruction/respiratory signal combinations performed similarly in the representation of the real-time motion. RESULTS: On average the target motion was significantly underrepresented and exceeded the 4DCBCT motion for 48%, 25%, and 40% of the time in the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) directions, respectively. The average underrepresentation for the LR, SI, and AP direction was 1.7 mm, 4.2 mm, and 2.5 mm, respectively. No difference could be shown between the reconstruction algorithms or respiratory signals in LR direction (FDK vs PICCS: P = .47, Calypso vs bellows: P = .19), SI direction (FDK vs PICCS: P = .49, Calypso vs bellows: P = .22), and AP direction (FDK vs PICCS: P = .62, Calypso vs bellows: P = .34). CONCLUSIONS: The 4DCBCT scans all underrepresented the real-time target motion. The selection of the reconstruction algorithm and respiratory signal for the 4DCBCT reconstruction does not have an impact on the reconstructed motion range.

Small tumor necrosis factor receptor biologics inhibit the tumor necrosis factor-p38 signalling axis and inflammation.

Despite anti-TNF therapy advancements for inflammatory diseases such as rheumatoid arthritis, the burden of diseases remains high. An 11-mer TNF peptide, TNF70-80, is known to stimulate selective functional responses compared to the parent TNF molecule. Here, we show that TNF70-80 binds to the TNF receptor, activating p38 MAP kinase through TNF receptor-associated factor 2. Using truncated TNFR mutants, we identify the sequence in TNFRI which enables p38 activation by TNF70-80. Peptides with this TNFRI sequence, such as TNFRI206-211 bind to TNF and inhibit TNF-induced p38 activation, respiratory burst, cytokine production and adhesion receptor expression but not F-Met-Leu-Phe-induced respiratory burst in neutrophils. TNFRI206-211 does not prevent TNF binding to TNFRI or TNF-induced stimulation of ERK, JNK and NF-κB. TNFRI206-211 inhibits bacterial lipopolysaccharide-induced peritonitis, carrageenan-induced and antigen-induced paw inflammation, and respiratory syncytial virus-induced lung inflammation in mice. Our findings suggest a way of targeting TNF-p38 pathway to treat chronic inflammatory disorders.

A comparison of gantry-mounted x-ray-based real-time target tracking methods.

PURPOSE: Most modern radiotherapy machines are built with a 2D kV imaging system. Combining this imaging system with a 2D-3D inference method would allow for a ready-made option for real-time 3D tumor tracking. This work investigates and compares the accuracy of four existing 2D-3D inference methods using both motion traces inferred from external surrogates and measured internally from implanted beacons. METHOD: Tumor motion data from 160 fractions (46 thoracic/abdominal patients) of Synchrony traces (inferred traces), and 28 fractions (7 lung patients) of Calypso traces (internal traces) from the LIGHT SABR trial (NCT02514512) were used in this study. The motion traces were used as the ground truth. The ground truth trajectories were used in silico to generate 2D positions projected on the kV detector. These 2D traces were then passed to the 2D-3D inference methods: interdimensional correlation, Gaussian probability density function (PDF), arbitrary-shape PDF, and the Kalman filter. The inferred 3D positions were compared with the ground truth to determine tracking errors. The relationships between tracking error and motion magnitude, interdimensional correlation, and breathing periodicity index (BPI) were also investigated. RESULTS: Larger tracking errors were observed from the Calypso traces, with RMS and 95th percentile 3D errors of 0.84-1.25 mm and 1.72-2.64 mm, compared to 0.45-0.68 mm and 0.74-1.13 mm from the Synchrony traces. The Gaussian PDF method was found to be the most accurate, followed by the Kalman filter, the interdimensional correlation method, and the arbitrary-shape PDF method. Tracking error was found to strongly and positively correlate with motion magnitude for both the Synchrony and Calypso traces and for all four methods. Interdimensional correlation and BPI were found to negatively correlate with tracking error only for the Synchrony traces. The Synchrony traces exhibited higher interdimensional correlation than the Calypso traces especially in the anterior-posterior direction. CONCLUSION: Inferred traces often exhibit higher interdimensional correlation, which are not true representation of thoracic/abdominal motion and may underestimate kV-based tracking errors. The use of internal traces acquired from systems such as Calypso is advised for future kV-based tracking studies. The Gaussian PDF method is the most accurate 2D-3D inference method for tracking thoracic/abdominal targets. Motion magnitude has significant impact on 2D-3D inference error, and should be considered when estimating kV-based tracking error.

Experience with an abdominal compression band for radiotherapy of upper abdominal tumours.

INTRODUCTION: Radiotherapy outcomes are influenced by treatment delivery geometric accuracy and organ-at-risk dose. The location of abdominal structures such as the liver, kidneys and tumour volumes can be strongly influenced by respiratory motion. This increases geometric uncertainty and dose to organs-at-risk. One common method of minimising respiratory motion is abdominal compression (AC). METHODS: Fifteen patients being treated for radiotherapy to upper abdominal tumours were analysed. Each patient underwent 2 four-dimensional computerised tomography (4D-CT) scans, one with and one without AC with a pneumatic compression belt. Liver and kidney positions were measured on the 4DCT scans at the peak inspiratory and expiratory respiratory phases. The patient received radiation therapy treatment planned on the CT data set with the technique (compression or no compression) that provided the least respiratory motion. RESULTS: There was no statistically significant motion difference over the sample population with AC for the kidneys or liver. Of the 14 evaluable patients, 4, 6 and 6 saw reduction in superior-inferior motion for left kidney, right kidney and liver respectively. The remainder either had negligible (<2 mm) or increase in motion with AC. For anterior-posterior motion, 2, 2 and 1 saw a reduction for left-kidney, right-kidney and liver respectively. CONCLUSION: AC through the use of a pneumatic compression belt was found to result in inconsistent reduction in kidney and liver respiratory motion. It is recommended that the effect of AC is evaluated on a per-patient basis.

Predictors of Liver Toxicity Following Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma.

PURPOSE: To identify risk factors associated with a decline in liver function after stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma. METHODS AND MATERIALS: Data were analyzed from patients with hepatocellular carcinoma treated on clinical trials of 6-fraction SBRT. Liver toxicity was defined as an increase in Child-Pugh (CP) score ≥2 three months after SBRT. Clinical factors, SBRT details, and liver dose-volume histogram (DVH) parameters were tested for association with toxicity using logistic regression. CP class B patients were analyzed separately. RESULTS: Among CP class A patients, 101 were evaluable, with a baseline score of A5 (72%) or A6 (28%). Fifty-three percent had portal vein thrombus. The median liver volume was 1286 cc (range, 766-3967 cc), and the median prescribed dose was 36 Gy (range, 27-54 Gy). Toxicity was seen in 26 patients (26%). Thrombus, baseline CP of A6, and lower platelet count were associated with toxicity on univariate analysis, as were several liver DVH-based parameters. Absolute and spared liver volumes were not significant. On multivariate analysis for CP class A patients, significant associations were found for baseline CP score of A6 (odds ratio [OR], 4.85), lower platelet count (OR, 0.90; median, 108 × 109/L vs 150 × 109/L), higher mean liver dose (OR, 1.33; median, 16.9 Gy vs 14.7 Gy), and higher dose to 800 cc of liver (OR, 1.11; median, 14.3 Gy vs 6.0 Gy). With 13 CP-B7 patients included or when dose to 800 cc of liver was replaced with other DVH parameters (eg, dose to 700 or 900 cc of liver) in the multivariate analysis, effective volume and portal vein thrombus were associated with an increased risk. CONCLUSIONS: Baseline CP scores and higher liver doses (eg, mean dose, effective volume, doses to 700-900 cc) were strongly associated with liver function decline 3 months after SBRT. A lower baseline platelet count and portal vein thrombus were also associated with an increased risk.

A Bayesian approach for three-dimensional markerless tumor tracking using kV imaging during lung radiotherapy.

The ability to monitor tumor motion without implanted markers can potentially enable broad access to more accurate and precise lung radiotherapy. A major challenge is that kilovoltage (kV) imaging based methods are rarely able to continuously track the tumor due to the inferior tumor visibility on 2D kV images. Another challenge is the estimation of 3D tumor position based on only 2D imaging information. The aim of this work is to address both challenges by proposing a Bayesian approach for markerless tumor tracking for the first time. The proposed approach adopts the framework of the extended Kalman filter, which combines a prediction and measurement steps to make the optimal tumor position update. For each imaging frame, the tumor position is first predicted by a respiratory-correlated model. The 2D tumor position on the kV image is then measured by template matching. Finally, the prediction and 2D measurement are combined based on the 3D distribution of tumor positions in the past 10 s and the estimated uncertainty of template matching. To investigate the clinical feasibility of the proposed method, a total of 13 lung cancer patient datasets were used for retrospective validation, including 11 cone-beam CT scan pairs and two stereotactic ablative body radiotherapy cases. The ground truths for tumor motion were generated from the the 3D trajectories of implanted markers or beacons. The mean, standard deviation, and 95th percentile of the 3D tracking error were found to range from 1.6-2.9 mm, 0.6-1.5 mm, and 2.6-5.8 mm, respectively. Markerless tumor tracking always resulted in smaller errors compared to the standard of care. The improvement was the most pronounced in the superior-inferior (SI) direction, with up to 9.5 mm reduction in the 95th-percentile SI error for patients with >10 mm 5th-to-95th percentile SI tumor motion. The percentage of errors with 3D magnitude <5 mm was 96.5% for markerless tumor tracking and 84.1% for the standard of care. The feasibility of 3D markerless tumor tracking has been demonstrated on realistic clinical scenarios for the first time. The clinical implementation of the proposed method will enable more accurate and precise lung radiotherapy using existing hardware and workflow. Future work is focused on the clinical and real-time implementation of this method.

The first patient treatment of electromagnetic-guided real time adaptive radiotherapy using MLC tracking for lung SABR.

BACKGROUND AND PURPOSE: Real time adaptive radiotherapy that enables smaller irradiated volumes may reduce pulmonary toxicity. We report on the first patient treatment of electromagnetic-guided real time adaptive radiotherapy delivered with MLC tracking for lung stereotactic ablative body radiotherapy. MATERIALS AND METHODS: A clinical trial was developed to investigate the safety and feasibility of MLC tracking in lung. The first patient was an 80-year old man with a single left lower lobe lung metastasis to be treated with SABR to 48Gy in 4 fractions. In-house software was integrated with a standard linear accelerator to adapt the treatment beam shape and position based on electromagnetic transponders implanted in the lung. MLC tracking plans were compared against standard ITV-based treatment planning. MLC tracking plan delivery was reconstructed in the patient to confirm safe delivery. RESULTS: Real time adaptive radiotherapy delivered with MLC tracking compared to standard ITV-based planning reduced the PTV by 41% (18.7-11cm3) and the mean lung dose by 30% (202-140cGy), V20 by 35% (2.6-1.5%) and V5 by 9% (8.9-8%). CONCLUSION: An emerging technology, MLC tracking, has been translated into the clinic and used to treat lung SABR patients for the first time. This milestone represents an important first step for clinical real-time adaptive radiotherapy that could reduce pulmonary toxicity in lung radiotherapy.

Systemic inflammation is an independent predictive marker of clinical outcomes in mucosal squamous cell carcinoma of the head and neck in oropharyngeal and non-oropharyngeal patients.

BACKGROUND: Currently there are very few biomarkers to identify head and neck squamous cell carcinoma (HNSCC) cancer patients at a greater risk of recurrence and shortened survival. This study aimed to investigate whether a marker of systemic inflammation, the neutrophil-to-lymphocyte ratio (NLR), was predictive of clinical outcomes in a heterogeneous cohort of HNSCC cancer patients. METHODS: We performed a retrospective analysis to identify associations between NLR and clinicopathological features to recurrence free survival (RFS) and overall survival (OS). Univariate analysis was used to identify associations and selected variables were included in multivariable Cox regression analysis to determine predictive value. RESULTS: A total of 145 patients with stage I-IV HNSCC that had undergone radiotherapy were analysed. Seventy-six of these patients had oropharyngeal cancer and 69 had non-oropharyngeal HNSCC and these populations were analysed separately. NLR was not associated to any clinicopathological variable. On univariate analysis, NLR showed associations with RFS and OS in both sub-populations. Multivariable analysis showed patients with NLR > 5 had shortened OS in both sub-populations but NLR > 5 only predicted RFS in oropharyngeal patients. Poor performance status predicted OS in both sub-populations and current smokers had shortened OS and RFS in non-oropharyngeal patients. CONCLUSIONS: The results show patients with NLR > 5 predict for shorter overall survival. Further prospective validation studies in larger cohorts are required to determine the clinical applicability of NLR for prognostication in HNSCC patients.

Neutrophil-to-lymphocyte ratio in head and neck cancer.

INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) is an index of systemic inflammatory burden in malignancy. An elevated NLR has been associated with poor prognosis in a number of cancer sites. We investigated its role in a cohort of patients with locally advanced head and neck cancer. METHODS: Eligible patients had primary mucosal squamous cell carcinoma treated with chemoradiotherapy and a minimum follow-up of 12 months (unless deceased). NLR was analysed as <5 vs. ≥5 and above and below the median. The primary endpoint was overall survival (OS) and secondary endpoints metastasis free survival and locoregional relapse free survival. Actuarial Kaplan-Meier statistics and log rank test were used. Univariate analysis for age (continuous), Eastern Cooperative Oncology Group performance status (0 vs. 1), gender (male vs. female), smoking (yes vs. no), American Joint Committee on Cancer stage (III vs. IV) and NLR (<5 vs. ≥5 and <3.3 vs. ≥3.3) were performed. RESULTS: Forty-six patients were included in this analysis. Median NLR was 3.3 (0.4-22.8). After a median follow-up of 34 months (13-47 months), the 2-year estimated OS, metastasis free survival and locoregional relapse free survival for NLR <5 vs. ≥5 were 89% vs. 61% (p = 0.017), 84% vs. 64% (p = 0.083) and 81% vs. 70% (p = 0.17) respectively. On univariate analysis NLR ≥5 (p = 0.025), older age (p = 0.01) and ECOG 1 (p = 0.025) were significant for OS. CONCLUSION: In this cohort of locally advanced head and neck cancer patients treated with chemoradiotherapy, pre-treatment NLR ≥5 was prognostic for mortality. Further studies are required to confirm these results and to assess the interaction with other prognostic factors.

Outcomes following definitive stereotactic body radiotherapy for patients with Child-Pugh B or C hepatocellular carcinoma.

PURPOSE: To report outcomes in patients with Child-Pugh B or C (CP B/C) hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS: A prospective study of SBRT was developed for patients with CP B7 or B8 unresectable HCC, <10 cm. Selected ineligible patients (e.g. CP>B8, >10 cm) treated off-study from 2004 to July 2012 were also reviewed. Patients were excluded if they were treated as a bridge-to-liver-transplant. RESULTS: 29 patients with CP B/C HCC were treated with SBRT (median dose 30 Gy in 6 fractions) from 2004 to December 2012. The majority had CP B7 liver function (69%) and portal vein tumor thrombosis (76%). The median survival was 7.9 months (95% CI: 2.8-15.1). Survival was significantly better in patients with CP=B7 and AFP≤4491 ng/mL. Of 16 evaluable patients, 63% had a decline in CP score by ≥2 points at 3 months. CONCLUSION: SBRT is a treatment option for selected HCC patients with small HCCs and modestly impaired (CP B7) liver function.