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There is increasing evidence supporting the efficacy of stereotactic body radiation therapy (SBRT) in the treatment of hepatocellular carcinoma (HCC). However, the role of SBRT has not yet been well defined within the treatment guidelines. We hypothesized that SBRT for HCC has a durable effect on tumor control and can be delivered safely. The research protocol and patient consent form were approved by the Medical Ethics Review Committee. Patients included in this retrospective study have been treated at our institution between January 2008 to December 2022. Eligibility criteria were diagnosis of HCC, case review in a multidisciplinary liver board, BCLC stage 0-A-B, noncirrhotic liver or liver with cirrhosis Child-Pugh class A, and a maximum of three lesions with a cumulative diameter of ≤ 6 cm. SBRT was considered for patients not suitable for resection or thermal ablation but eligible for TACE. Patients with relapses after surgery, thermal ablation or TACE or patients awaiting transplant were also candidates for SBRT. Exclusion criteria were uncontrolled portal hypertension and active hepatitis infection. SBRT was delivered in 6 fractions of 8 or 9 Gy applying a risk adaptive approach. The primary endpoint was local (target) control (LC). Secondary endpoints were time to (target and non-target) progression (TTP), overall survival (OS), best local response and toxicity. Treatment response was assessed for the purpose of this study on CT or MRI images by an expert radiologist using mRECIST criteria. Toxicity was defined as an SBRT related grade ≥ 3 event according to the CTCAE v4.03 scoring system. The Kaplan-Meier method was applied to analyze LC, TTP, and OS. A total of 52 patients received SBRT at our institution and 51 were included in this study. One patient objected to the use of his data and this patient was excluded. Median follow-up was 2.1 years (0.5–14.8) for tumor response and 2.3 years (0.5–14.8) for OS. Median tumor size was 26 mm (8–68). Median number of treated tumors per patient was 1 (1–3). Median LC was not reached. There was 1 local recurrence after 21 months. At 1, 2 and 5 years LC rates were 100%, 95% and 95% respectively. Median TTP was 45.6 months [95% CI, 16.1 to not reached]. Median OS was 7.1 years [95% CI, 4.9 to not reached]. Best local target response was 100%. None of the patients in this study have experienced SBRT related CTCAE grade ≥ 3 toxicity. Thirteen patients underwent a liver transplantation after SBRT with a median time interval between baseline and transplant of 7 months (3–16). SBRT resulted in excellent long-term local control rates and absence of severe toxicity in a group of HCC patients with well compensated liver cirrhosis, disease confined to the liver, limited size and number of treated tumors, and not eligible for surgery or thermal ablation but eligible for TACE. The reported outcomes compared favorably with other local therapies. SBRT should be considered as one of the available local treatment options for HCC. [ABSTRACT FROM AUTHOR]

Purpose/objectives: To evaluate if stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) has a durable effect on tumor control and can be delivered safely., Materials/methods: Patients included in this retrospective study have been treated at our institution from January 2008 to December 2022. Eligibility criteria were diagnosis of HCC, BCLC stage 0-A-B, non-cirrhotic liver or liver with cirrhosis Child-Pugh class A, and a maximum of three lesions with a cumulative diameter of ≤ 6 cm. Patients with relapses after surgery, thermal ablation or TACE or patients awaiting transplant were also candidates for SBRT. SBRT was delivered in 6 fractions of 8 or 9 Gy. The primary endpoint was local (target) control (LC). Secondary endpoints were time to progression (TTP), overall survival (OS), response rate (RR) and toxicity., Results: A total of 52 patients received SBRT at our institution and 51 were included in this study. One patient objected and was excluded. Median follow-up was 2.1 years for LC and 2.3 years for OS. Median tumor size was 26 mm. LC rates at 1, 2, and 5 years were 100 %, 95 % and 95 % respectively. Median TTP was 45.6 months. Median OS was 7.1 years. RR was 96 %. No patients in this study have experienced SBRT related CTC AE grade ≥ 3 toxicity., Conclusion: SBRT resulted in excellent long-term local control rates and absence of severe toxicity in a group of HCC patients. The reported outcomes compare favorably with other local therapies. SBRT should be considered as one of the available local treatment options for HCC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background and Purpose: Uveal melanoma (UM) is the most common primary ocular malignancy. We compared fractionated stereotactic radiotherapy (SRT) with proton therapy, including toxicity risks for UM patients., Materials and Methods: For a total of 66 UM patients from a single center, SRT dose distributions were compared to protons using the same planning CT. Fourteen dose-volume parameters were compared in 2-Gy equivalent dose per fraction (EQD2). Four toxicity profiles were evaluated: maculopathy, optic-neuropathy, visual acuity impairment (Profile I); neovascular glaucoma (Profile II); radiation-induced retinopathy (Profile III); and dry-eye syndrome (Profile IV). For Profile III, retina Mercator maps were generated to visualize the geographical location of dose differences., Results: In 9/66 cases, (14 %) proton plans were superior for all dose-volume parameters. Higher T stages benefited more from protons in Profile I, especially tumors located within 3 mm or less from the optic nerve. In Profile II, only 9/66 cases resulted in a better proton plan. In Profile III, better retina volume sparing was always achievable with protons, with a larger gain for T3 tumors. In Profile IV, protons always reduced the risk of toxicity with a median RBE-weighted EQD2 reduction of 15.3 Gy., Conclusions: This study reports the first side-by-side imaging-based planning comparison between protons and SRT for UM patients. Globally, while protons appear almost always better regarding the risk of optic-neuropathy, retinopathy and dry-eye syndrome, for other toxicity like neovascular glaucoma, a plan comparison is warranted. Choice would depend on the prioritization of risks., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: E. Fleury: The Department of Radiotherapy (Erasmus Medical Center Cancer Institute, The Netherlands) has research collaborations with Elekta AB, Stockholm, Sweden, Accuray Inc., Sunnyvale, CA, USA, Varian, Palo Alto, CA, USA, RaySearch Laboratories, Stockholm, Sweden, outside the submitted work. Prof. dr. Pignol: Prof. dr. Pignol was senior vice president, chief medical and technology officer at Accuray Inc., Sunnyvale, CA, USA until February 2023. Prof. dr. Hoogeman: Prof. dr. Hoogeman reports grants from Netherlands Organization for Scientific Research, grants from Varian, a Siemens Healthineers Company, Palo Alto, California, USA, during the conduct of the study; being a Member of advisory board Accuray, Sunnyvale, USA; being a participant/presenter at Accuray Thinktank Meeting on Prostate cancer, outside the submitted work; and The Department of Radiotherapy (Erasmus Medical Center Cancer Institute, The Netherlands) has research collaborations with Elekta AB, Stockholm, Sweden, Accuray Inc., Sunnyvale, CA, USA, Varian, Palo Alto, CA, USA, RaySearch Laboratories, Stockholm, Sweden, outside the submitted work., (© 2024 The Authors.)

Purpose: To compare transarterial chemoembolization delivered with drug eluting beads (TACE-DEB) with stereotactioc body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC) in a multicenter randomized trial., Methods and Materials: Patients were included if they were eligible for TACE. They could also be recruited if they required treatment prior to liver transplantation. A maximum of four TACE-DEB procedures and ablation after incomplete TACE-DEB were both allowed. SBRT was delivered in six fractions of 8-9Gy. Primary end point was time to progression (TTP). Secondary endpoints were local control (LC), overall survival (OS), response rate (RR), toxicity, and quality of life (QoL). The calculated sample size was 100 patients., Results: Between May 2015 and April 2020, 30 patients were randomized to the study. Due to slow accrual the trial was closed prematurely. Two patients in the SBRT arm were considered ineligible leaving 16 patients in the TACE-DEB arm and 12 in the SBRT arm. Median follow-up was 28.1 months. Median TTP was 12 months for TACEDEB and 19 months for SBRT (p=0.15). Median LC was 12 months for TACE-DEB and >40 months (not reached) for SBRT (p=0.075). Median OS was 36.8 months for TACEDEB and 44.1 months for SBRT (p=0.36). A post-hoc analysis showed 100% for SBRT 1- and 2-year LC, and 54.4% and 43.6% for TACE-DEB (p=0.019). Both treatments resulted in RR>80%. Three episodes of possibly related toxicity grade ≥3 were observed after TACE-DEB. No episodes were observed after SBRT. QoL remained stable after both treatment arms., Conclusions: In this trial, TTP after TACE-DEB was not significantly improved by SBRT, while SBRT showed higher local antitumoral activity than TACE-DEB, without detrimental effects on OS, toxicity and QoL. To overcome poor accrual in randomized trials that include SBRT, and to generate evidence for including SBRT in treatment guidelines, international cooperation is needed., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Using fiducial-marker-based robotic respiratory tumor tracking, we treated perihilar cholangiocarcinoma patients in the STRONG trial with 15 daily fractions of 4 Gy. For each of the included patients, in-room diagnostic-quality repeat CTs (rCT) were acquired pre- and post-dose delivery in 6 treatment fractions to analyze inter- and intrafraction dose variations. Planning CTs (pCTs) and rCTs were acquired in expiration breath-hold. Analogous to treatment, spine and fiducials were used to register rCTs with pCTs. In each rCT, all OARs were contoured, and the target was rigidly copied from the pCT based on grey values. The rCTs acquired were used to calculate the doses to be delivered through the treatment-unit settings. On average, target doses in rCTs and pCTs were similar. However, due to target displacements relative to the fiducials in rCTs, 10% of the rCTs showed PTV coverage losses of >10%. Although target coverages had been planned below desired values in order to protect OARs, many pre-rCTs contained OAR constraint violations: 44.4% for the 6 major constraints. Most OAR dose differences between pre- and post-rCTs were not statistically significant. The dose deviations observed in repeat CTs represent opportunities for more advanced adaptive approaches to enhancing SBRT treatment quality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Paronetto, den Toom, Milder, van Norden, Baak, Heijmen and Méndez Romero.)

Background and Purpose: Stereotactic body radiotherapy (SBRT) has been proven to be beneficial for several disease sites in the (lower) abdomen. However, the quality of the treatment plan, based on a single planning computed tomography (CT), can be compromised due to large inter-fraction motion of the target and organs at risk (OARs) in this anatomical region. The aim of this study was to investigate the feasibility of online adaptive SBRT treatments on a robotic radiosurgery system and to record estimated total treatment times., Materials and Methods: For two disease sites, locally advanced pancreatic cancer (LAPC) and oligometastatic lymph nodes, four patients with repeat CTs were included in the feasibility study. Quick treatment plan templates were generated based on the planning CT and validated by running them on the plan and fraction CTs. For two cases a dummy run was performed and the individual steps were timed. Dose delivery was the largest contributor to the total treatment time, followed by contour adaptation., Results: Running the quick plan templates resulted in plans similar to unrestricted plans, obeying the OAR constraints. The dummy runs showed that online adaptive treatments were completed in 64 to 83 min respectively for oligometastases and LAPC, comparable to other clinically available solutions., Conclusions: This study showed the feasibility of online re-planning for two challenging disease sites within a clinically acceptable time frame on a robotic radiosurgery system, making use of commercially available elements that are not integrated by the vendor., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The Erasmus MC Cancer Institute has research collaborations with Elekta AB, Stockholm, Sweden and Accuray Inc, Sunnyvale, USA, and Varian, Paolo Alto, USA., (© 2022 The Author(s).)

Purpose: To determine the dosimetric impact of using unedited autocontours in daily plan adaptation of patients with locally advanced pancreatic cancer (LAPC) treated with stereotactic body radiotherapy using tumor tracking., Materials and Methods: The study included 98 daily CT scans of 35 LAPC patients. All scans were manually contoured (MAN), and included the PTV and main organs-at-risk (OAR): stomach, duodenum and bowel. Precision and MIM deformable image registration (DIR) methods followed by contour propagation were used to generate autocontour sets on the daily CT scans. Autocontours remained unedited, and were compared to MAN on the whole organs and at 3, 1 and 0.5 cm from the PTV. Manual and autocontoured OAR were used to generate daily plans using the VOLO™ optimizer, and were compared to non-adapted plans. Resulting planned doses were compared based on PTV coverage and OAR dose-constraints., Results: Overall, both algorithms reported a high agreement between unclipped MAN and autocontours, but showed worse results when being evaluated on the clipped structures at 1 cm and 0.5 cm from the PTV. Replanning with unedited autocontours resulted in better OAR sparing than non-adapted plans for 95% and 84% plans optimized using Precision and MIM autocontours, respectively, and obeyed OAR constraints in 64% and 56% of replans., Conclusion: For the majority of fractions, manual correction of autocontours could be avoided or be limited to the region closest to the PTV. This practice could further reduce the overall timings of adaptive radiotherapy workflows for patients with LAPC., Competing Interests: All authors are employed by the Erasmus MC. MM and MH report serving as an advisory board member for Accuray during the conduct of the study., (Copyright © 2022 Magallon-Baro, Milder, Granton, Toom, Nuyttens and Hoogeman.)

Background: In unresectable pCCA, the standard of care is palliative chemotherapy. We investigated the feasibility and safety of adding stereotactic body radiation therapy (SBRT) after chemotherapy., Methods: Patients with unresectable pCCA, stage T1-T4N0-N1M0, ECOG 0-1, having finished 6-8 cycles of cisplatin and gemcitabine without disease progression were eligible. SBRT was planned in 15 fractions of 3.0-4.5 Gy. The primary endpoints were feasibility (defined as completing SBRT as planned) and toxicity, evaluated within 3 months after SBRT (CTCAE v4.03). A conventional "3 + 3" design was used, corresponding to a sample size of 6 patients. Dose-limiting toxicity (DLT) was defined as grade ≥ 4 hepatobiliary or grade ≥ 3 gastrointestinal toxicity. The secondary endpoints, measured from the start of radiotherapy, were local control, progression-free survival, overall survival, and quality of life (QoL). ClinicalTrials.gov identifier: NCT03307538., Results: Six patients were enrolled between November 2017 and March 2020. SBRT was delivered as planned. All patients were treated with 60Gy (15 × 4.0Gy). No SBRT-related DLT was observed. The most common grade ≥ 3 toxicity was cholangitis ( n = 5). The median follow-up was 14 months. The 12-month local control rate was 80%. We observed no substantial changes in QoL., Conclusion: In patients with unresectable pCCA with stable disease after palliative chemotherapy, adding SBRT is feasible and safe. The observed local control merits an additional evaluation of effectiveness.

Recently, VOLO™ was introduced as a new optimizer for CyberKnife® planning. In this study, we investigated possibilities to improve treatment plans for MLC-based prostate SBRT with enhanced peripheral zone dose while sparing the urethra, and central lung tumors, compared to existing Sequential Optimization (SO). The primary focus was on reducing OAR doses. For 25 prostate and 25 lung patients treated with SO plans, replanning with VOLO™ was performed with the same planning constraints. For equal PTV coverage, almost all OAR plan parameters were improved with VOLO™. For prostate patients, mean rectum and bladder doses were reduced by 34.2% (P < 0.001) and 23.5% (P < 0.001), with reductions in D 0.03cc of 3.9%, 11.0% and 3.1% for rectum, mucosa and bladder (all P ≤ 0.01). Urethra D 5% and D 10% were 3.8% and 3.0% lower (P ≤ 0.002). For lung patients, esophagus, main bronchus, trachea, and spinal cord D 0.03cc was reduced by 18.9%, 11.1%, 16.1%, and 13.2%, respectively (all P ≤ 0.01). Apart from the dosimetric advantages of VOLO™ planning, average reductions in MU, numbers of beams and nodes for prostate/lung were 48.7/32.8%, 26.5/7.9% and 13.4/7.9%, respectively (P ≤ 0.003). VOLO™ also resulted in reduced delivery times with mean/max reductions of: 27/43% (prostate) and 15/41% (lung), P  < 0.001. Planning times reduced from 6 h to 1.1 h and from 3 h to 1.7 h for prostate and lung, respectively. The new VOLO™ planning was highly superior to SO planning in terms of dosimetric plan quality, and planning and delivery times., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: To investigate the quality of treatment plans of spinal radiosurgery derived from different planning and delivery systems. The comparisons include robotic delivery and intensity modulated arc therapy (IMAT) approaches. Multiple centers with equal systems were used to reduce a bias based on individual's planning abilities. The study used a series of three complex spine lesions to maximize the difference in plan quality among the various approaches., Methods: Internationally recognized experts in the field of treatment planning and spinal radiosurgery from 12 centers with various treatment planning systems participated. For a complex spinal lesion, the results were compared against a previously published benchmark plan derived for CyberKnife radiosurgery (CKRS) using circular cones only. For two additional cases, one with multiple small lesions infiltrating three vertebrae and a single vertebra lesion treated with integrated boost, the results were compared against a benchmark plan generated using a best practice guideline for CKRS. All plans were rated based on a previously established ranking system., Results: All 12 centers could reach equality (n = 4) or outperform (n = 8) the benchmark plan. For the multiple lesions and the single vertebra lesion plan only 5 and 3 of the 12 centers, respectively, reached equality or outperformed the best practice benchmark plan. However, the absolute differences in target and critical structure dosimetry were small and strongly planner-dependent rather than system-dependent. Overall, gantry-based IMAT with simple planning techniques (two coplanar arcs) produced faster treatments and significantly outperformed static gantry intensity modulated radiation therapy (IMRT) and multileaf collimator (MLC) or non-MLC CKRS treatment plan quality regardless of the system (mean rank out of 4 was 1.2 vs. 3.1, p = 0.002)., Conclusions: High plan quality for complex spinal radiosurgery was achieved among all systems and all participating centers in this planning challenge. This study concludes that simple IMAT techniques can generate significantly better plan quality compared to previous established CKRS benchmarks.