Magnetic resonance-guided stereotactic body radiation therapy (MRgSBRT) for oligometastatic patients: a single-center experience

Data from oligometastatic patients treated with MRgRT from February 2017 to March 2021 at Policlinico Universitario “Agostino Gemelli” IRCCS of Rome, Italy, were retrospectively collected and analysed. All patients were treated using a 0.35 T MRgRT unit (MRIdian, ViewRay Inc., Mountain View, CA, USA), initially using the Cobalt-60 version, consisting of a tri-cobalt-60-ringed gantry with on-board MRI imaging [7]. Its updated Linac version, which couples a 0.35 T MRI scanner with a 6-MV flattering filter-free (FFF) Linac [8], was used after an upgrade that took place in February 2018.

Patients ≥ 18 years old, with the Eastern Cooperative Oncology Group (ECOG) performance score 0–2, presenting up to five inoperable metastases, eligible for MRgSBRT, and able to sign an informed consent were included. Patients who had already undergone RT on the same anatomical site with overlap with the previously treated radiation volume were excluded. No size-related cut-off thresholds for the lesion size were established.

All patients underwent dedicated treatment simulation on the MRIdian system.

Patients with abdominal metastases were instructed to fast at least 3 h before the simulation and therapy sessions to increase the reproducibility of the treatment. All patients were immobilized in a supine position using a customized immobilization device Fluxboard (Fluxboard™, MacroMedics, The Netherlands). True fast imaging (TRUFI) MR scans were acquired with different acquisition protocols, either free breathing (FB) 25-s MR scans or breath-hold inspiration (BHI) 17- or 25-s MR scans, to assess tumour and OAR motion.

A real-time sagittal cine TRUFI MRI sequence (4/8 frames/s) was used to assess reproducibility and patient tolerance to gating. If the patient was unable to tolerate simulation under BHI conditions, he/she was considered for FB treatment.

In this phase, several parameters were defined in order to customize the treatment, such as the gating target structure (which could be the lesion itself or a surrogate), the boundary values, tracking algorithms, confidence rating, and percentage of region of interest (ROI%).

A standard simulation CT scan was performed with the same immobilization system to obtain the electron density information for the dose calculation. After a deformable coregistration of the CT on the simulation MR used as primary imaging, contouring was performed according to the RTOG guidelines [9, 10], using the information obtained from coregistered diagnostic imaging (MR, CT, or 18FDG PET-CT).

The GTV was considered equal to the CTV, and the CTV-PTV margin was set at 3–5 mm, depending on clinical judgement and intrafraction motion. Planning was performed with the MRIdian treatment planning system (ViewRay Inc., Mountain View, CA, USA) through a Monte Carlo calculation algorithm with a step-and-shoot intensity-modulated radiation technique [11], including the influence of 0.35 T on the dose calculation.

PTV coverage was assessed according to ICRU 83 [12] or ICRU 91 [13] recommendations, and AAPM Task Group 101 [14] constraints were used for dose evaluation to OARs.

Prior to each treatment fraction, a new 17- or 25-s MR scan was acquired, either FB or BHI, depending on the case, to assess patient alignment and make set-up corrections if needed.

If the indication for SMART was given by attending physician, deformable contour registration, contour adjustment, dose prediction, treatment plan re-optimization, and secondary Monte Carlo-based quality assurance (QA) were performed, as described previously [15, 16]. After selecting the most appropriate sagittal plane for gating and setting the recalled parameters defined in the simulation phase, the treatment was delivered through daily online cine-MR monitoring.

Toxicities were considered acute if recorded up to 90 days after the end of treatment or late if afterwards. The Common Terminology Criteria for Adverse Events (CTCAE) scale version 5.0 was used for their scoring [17].

Local and systemic response to treatment were assessed according to RECIST criteria, according to a follow-up schedule that included instrumental re-evaluation every 3–6 months with contrast-enhanced MRI, contrast-enhanced CT, or 18FDG PET-CT, depending on clinical judgement [18]. Clinical and dosimetric data were also collected.

The conformity index (CI) and the homogeneity index (HI) of lesions representing the conformity between the prescribed dose area and PTV and the degree of uniformity within the target were calculated according to the RTOG definitions [19].

Furthermore, patients were classified according to the status of metastatic disease as defined by Guckenberger et al. [20]. OS was calculated from the date of primary tumour diagnosis to the date of the last follow-up or death. Overall and local progression-free survival (PFS and LPFS) were calculated from the date of end of RT treatment to the date of overall and local progression, respectively. OS, PFS, and LPFS were estimated using the Kaplan–Meier method.

The objective response rate (ORR), including complete response (CR) and partial response (PR), was evaluated for the irradiated lesions. Clinical benefit (CB) included ORR and stable disease (SD).

The analysed variables were patient-dependent (e.g. age, gender, ECOG), disease-dependent (e.g. site of primary cancer, site of treated metastasis, oligometastatic disease or induced oligometastatic disease, synchronous or metachronous metastatic presentation, subsequent combined treatments), and treatment-dependent (e.g. SMART application, gating phase, BED, GTV volume) (see supplementary materials for complete datasets). These parameters were correlated with each survival outcome on “per-lesion” basis using the univariate analysis with the Kaplan–Meier method. Then, Cox regression multivariate analysis was performed using the variables that resulted statistically significant from the univariate analysis. Statistical significance was defined as p-value < 0,05. Results were reported as odds radio with 95% confidence interval.

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