Magnetic Resonance-Guided Stereotactic Body Radiotherapy of Liver Tumors: Initial Clinical Experience and Patient-Reported Outcomes

Purpose/ObjectiveStereotactic body radiation therapy (SBRT) has emerged as a valid treatment alternative for non-resectable liver metastases or hepatocellular carcinomas (HCC). Magnetic resonance (MR) guided SBRT has a high potential of further improving treatment quality, allowing for higher, tumoricidal irradiation doses whilst simultaneously sparing organs at risk. However, data on treatment outcome and patient acceptance is still limited.Material/MethodsWe performed a subgroup analysis of an ongoing prospective observational study comprising patients with liver metastases or HCC. Patients were treated with ablative MR-guided SBRT at the MRIdian Linac in the Department of Radiation Oncology at Heidelberg University Hospital between January 2019 and February 2020. Local control (LC) and overall survival (OS) analysis was performed using the Kaplan–Meier method. An in-house designed patient-reported outcome questionnaire was used to measure patients’ experience with the MR-Linac treatment. Toxicity was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v. 5.0).ResultsTwenty patients (with n = 18 metastases; n = 2 HCC) received MR-guided SBRT for in total 26 malignant liver lesions. Median biologically effective dose (BED at α/β = 10) was 105.0 Gy (range: 67.2–112.5 Gy) and median planning target volume was 57.20 ml (range: 17.4–445.0 ml). Median treatment time was 39.0 min (range: 26.0–67.0 min). At 1-year, LC was 88.1% and OS was 84.0%. Grade I° gastrointestinal toxicity °occurred in 30.0% and grade II° in 5.0% of the patients with no grade III° or higher toxicity. Overall treatment experience was rated positively, with items scoring MR-Linac staff’s performance and items concerning the breath hold process being among the top positively rated elements. Worst scored items were treatment duration, positioning and low temperature.ConclusionMR-guided SBRT of liver tumors is a well-tolerated and well-accepted treatment modality. Initial results are promising with excellent local control and only mildest toxicity. However, prospective studies are warranted to truly assess the potential of MR-guided liver SBRT and to identify which patients profit most from this new versatile technology

Leaf-individual calibration for a double stack multileaf collimator in photon radiotherapy

Background and Purpose: In online adaptive stereotactic body radiotherapy treatments, linear accelerator delivery accuracy is essential. Recently introduced double stack multileaf collimators (MLCs) have new facets in their calibration. We established a radiation-based leaf-individual calibration (LIMCA) method for double stack MLCs. Materials and Methods: MLC leaf positions were evaluated from four cardinal angles with test patterns at measurement positions throughout the radiation field on EBT3 radiochromic film for each single stack. The accuracy of the method and repeatability of the results were assessed. The effect of MLC positioning errors was characterized for a measured output factor curve and a clinical patient plan. Results: All positions in the motor step – position calibration file were optimized in the established LIMCA method. The resulting double stack mean accuracy for all angles was 0.2 ± 0.1 mm for X1 (left bank) and 0.2 ± 0.2 mm for X2 (right bank). The accuracy of the leaf position evaluation was 0.2 mm (95% confidence level). The MLC calibration remained stable over four months. Small MLC leaf position errors (e.g. 1.2 mm field size reduction) resulted in important dose errors (−5.8 %) for small quadratic fields of 0.83 × 0.83 cm2. Single stack position accuracy was essential for highly modulated treatment plans. Conclusions: LIMCA is a new double stack MLC calibration method that increases treatment accuracy from four angles and for all moving leaves

Stereotactic body radiotherapy of lymph node metastases under MR-guidance: First clinical results and patient-reported outcomes

Objective!#!Stereotactic body radiotherapy (SBRT) is a noninvasive treatment option for lymph node metastases (LNM). Magnetic resonance (MR)-guidance offers superior tissue contrast and enables treatment of targets in close vicinity to radiosensitive organs at risk (OAR). However, literature on MR-guided SBRT of LNM is scarce with no report on outcome parameters.!##!Materials and methods!#!We report a subgroup analysis of a prospective observational study comprising patients with LNM. Patients received MR-guided SBRT at our MRIdian Linac (ViewRay Inc., Mountain View, CA, USA) between January 2019 and February 2020. Local control (LC), progression-free survival (PFS) and overall survival (OS) analysis were performed using the Kaplan-Meier method with log rank test to test for significance (p < 0.05). Our patient-reported outcome questionnaire was utilized to evaluate patients' perspective. The CTCAE (Common Terminology Criteria for Adverse Events) v. 5.0 was used to describe toxicity.!##!Results!#!Twenty-nine patients (72.4% with prostate cancer; 51.7% with no distant metastases) received MR-guided SBRT for in total 39 LNM. Median dose was 27 Gy in three fractions, prescribed to the 80% isodose. At 1‑year, estimated LC, PFS and OS were 92.6, 67.4 and 100.0%. Compared to baseline, six patients (20.7%) developed new grade I toxicities (mainly fatigue). One grade II toxicity occurred (fatigue), with no adverse event grade ≥III. Overall treatment experience was rated particularly positive, while the technically required low room temperature still represents the greatest obstacle in the pursuit of the ideal patient acceptance.!##!Conclusion!#!MR-guided SBRT of LNM was demonstrated to be a well-accepted treatment modality with excellent preliminary results. Future studies should evaluate the clinical superiority to conventional SBRT

Comparison of different dose accumulation strategies to estimate organ doses after stereotactic magnetic resonance-guided adaptive radiotherapy

Abstract Introduction Re-irradiation is frequently performed in the era of precision oncology, but previous doses to organs-at-risk (OAR) must be assessed to avoid cumulative overdoses. Stereotactic magnetic resonance-guided online adaptive radiotherapy (SMART) enables highly precise ablation of tumors close to OAR. However, OAR doses may change considerably during adaptive treatment, which complicates potential re-irradiation. We aimed to compare the baseline plan with different dose accumulation techniques to inform re-irradiation. Patients & methods We analyzed 18 patients who received SMART to lung or liver tumors inside prospective databases. Cumulative doses were calculated inside the planning target volumes (PTV) and OAR for the adapted plans and theoretical non-adapted plans via (1) cumulative dose volume histograms (DVH sum plan) and (2) deformable image registration (DIR)-based dose accumulation to planning images (DIR sum plan). We compared cumulative dose parameters between the baseline plan, DVH sum plan and DIR sum plan using equivalent doses in 2 Gy fractions (EQD2). Results Individual patients presented relevant increases of near-maximum doses inside the proximal bronchial tree, spinal cord, heart and gastrointestinal OAR when comparing adaptive treatment to the baseline plans. The spinal cord near-maximum doses were significantly increased in the liver patients (D2% median: baseline 6.1 Gy, DIR sum 8.1 Gy, DVH sum 8.4 Gy, p = 0.04; D0.1 cm³ median: baseline 6.1 Gy, DIR sum 8.1 Gy, DVH sum 8.5 Gy, p = 0.04). Three OAR overdoses occurred during adaptive treatment (DIR sum: 1, DVH sum: 2), and four more intense OAR overdoses would have occurred during non-adaptive treatment (DIR sum: 4, DVH sum: 3). Adaptive treatment maintained similar PTV coverages to the baseline plans, while non-adaptive treatment yielded significantly worse PTV coverages in the lung (D95% median: baseline 86.4 Gy, DIR sum 82.4 Gy, DVH sum 82.2 Gy, p = 0.006) and liver patients (D95% median: baseline 87.4 Gy, DIR sum 82.1 Gy, DVH sum 81.1 Gy, p = 0.04). Conclusion OAR doses can increase during SMART, so that re-irradiation should be planned based on dose accumulations of the adapted plans instead of the baseline plan. Cumulative dose volume histograms represent a simple and conservative dose accumulation strategy

Dosimetric Benefit of Adaptive Magnetic Resonance-Guided Stereotactic Body Radiotherapy of Liver Metastases

(1) Background: To assess dosimetry benefits of stereotactic magnetic resonance (MR)-guided online adaptive radiotherapy (SMART) of liver metastases. (2) Methods: This is a subgroup analysis of an ongoing prospective registry including patients with liver metastases. Patients were treated at the MRIdian Linac between February 2020 and April 2022. The baseline plan was recalculated based on the updated anatomy of the day to generate the predicted plan. This predicted plan could then be re-optimized to create an adapted plan. (3) Results: Twenty-three patients received 30 SMART treatment series of in total 36 liver metastases. Most common primary tumors were colorectal- and pancreatic carcinoma (26.1% respectively). Most frequent fractionation scheme (46.6%) was 50 Gy in five fractions. The adapted plan was significantly superior compared to the predicted plan in regard to planning-target-volume (PTV) coverage, PTV overdosing, and organs-at-risk (OAR) dose constraints violations (91.5 vs. 38.0%, 6 vs. 19% and 0.6 vs. 10.0%; each p p < 0.001). Mean total duration of SMART was 72.4 min. (4) Conclusions: SMART offers individualized ablative irradiation of liver metastases tailored to the daily anatomy with significant superior tumor coverage and improved sparing of OAR