MR-guided adaptive versus ITV-based stereotactic body radiotherapy for hepatic metastases (MAESTRO): a randomized controlled phase II trial

Abstract

Background Stereotactic body radiotherapy (SBRT) is an established local treatment method for patients with hepatic oligometastasis or oligoprogression. Liver metastases often occur in close proximity to radiosensitive organs at risk (OARs). This limits the possibility to apply sufficiently high doses needed for optimal local control. Online MR-guided radiotherapy (oMRgRT) is expected to hold potential to improve hepatic SBRT by offering superior soft-tissue contrast for enhanced target identification as well as the benefit of gating and daily real-time adaptive treatment. The MAESTRO trial therefore aims to assess the potential advantages of adaptive, gated MR-guided SBRT compared to conventional SBRT at a standard linac using an ITV (internal target volume) approach. Methods This trial is conducted as a prospective, randomized, three-armed phase II study in 82 patients with hepatic metastases (solid malignant tumor, 1–3 hepatic metastases confirmed by magnetic resonance imaging (MRI), maximum diameter of each metastasis ≤ 5 cm (in case of 3 metastases: sum of diameters ≤ 12 cm), age ≥ 18 years, Karnofsky Performance Score ≥ 60%). If a biologically effective dose (BED) ≥ 100 Gy (α/β = 10 Gy) is feasible based on ITV-based planning, patients will be randomized to either MRgRT or ITV-based SBRT. If a lesion cannot be treated with a BED ≥ 100 Gy, the patient will be treated with MRgRT at the highest possible dose. Primary endpoint is the non-inferiority of MRgRT at the MRIdian Linac® system compared to ITV-based SBRT regarding hepatobiliary and gastrointestinal toxicity CTCAE III or higher. Secondary outcomes investigated are local, locoregional (intrahepatic) and distant tumor control, progression-free survival, overall survival, possible increase of BED using MRgRT if the BED is limited with ITV-based SBRT, treatment-related toxicity, quality of life, dosimetric parameters of radiotherapy plans as well as morphological and functional changes in MRI. Potential prognostic biomarkers will also be evaluated. Discussion MRgRT is known to be both highly cost- and labor-intensive. The MAESTRO trial aims to provide randomized, higher-level evidence for the dosimetric and possible consecutive clinical benefit of MR-guided, on-table adaptive and gated SBRT for dose escalation in critically located hepatic metastases adjacent to radiosensitive OARs. Trial registration The study has been prospectively registered on August 30th, 2021: Clinicaltrials.gov, “Magnetic Resonance-guided Adaptive Stereotactic Body Radiotherapy for Hepatic Metastases (MAESTRO)”, NCT05027711.

Stereotactic Body Radiotherapy (SBRT) of Pancreatic Cancer—A Critical Review and Practical Consideration

“…Stereotactic MR-guided adaptive radiotherapy (SMART) is a technique combining X-ray beam delivery, daily adaptive treatment planning, and gating/tracking capability using continuous cine MR images. It is expected to constitute the gold standard for future treatment of not only pancreatic cancer but also cancer at many other sites [ 96 , 97 ].…”

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

“…Furthermore, as in the study presented here, patients were included regardless of the tumor localization within the liver. Our currently recruiting MAESTRO study (Magnetic Resonance-guided Adaptive Stereotactic Body Radiotherapy for Hepatic Metastases) investigates the benefit of SMART in liver metastases compared with conventional, CBCT guided SBRT [ 36 ]. If high dose SBRT is feasible (>100 Gy BED; alpha/beta = 10 Gy), patients are randomized between SMART and CBCT guided treatment.…”

MRI-LINAC: A transformative technology in radiation oncology

“…The ongoing MAESTRO randomized controlled phase 2 trial is testing the non-inferiority of MRI guided adaptive radiation versus ITV-based SBRT for hepatic metastases for hepatobiliary and gastrointestinal ≥ grade 3 toxicities (88). The secondary outcomes include local regional and distant tumor control, progression freesurvival, overall survival, and the possibility of increase of BED using MRI guided radiotherapy if the BED is limited with ITV base SBRT.…”