We demonstrate that Monaco is able to accurately generate safe MR-Linac radiotherapy treatment plans for glioma patients that achieve planning objectives. We observed that for coplanar beam arrangements, MR-Linac treatments have lower homogeneity, but higher dose conformity and equivalent dose falloff outside of the target, when compared with CBCT-Linac. Conventional CBCT-Linac with non-coplanar beams can potentially achieve better dose falloff than MR-Linac, but only coplanar beam arrangements were used to standardize comparisons. MR-Linac treatment plans had more heterogenous dose distributions, which is consistent with the observed small but statistically significant increase in PTV D50%, D5%, and D2%. This is also consistent with previous reports showing higher heterogeneity and higher median V100% for MR-Linac plans compared with CBCT-Linac . Similarly, a very small but statistically significant increase in Brainstem D0.1cc, each Globe D0.03cc, and each Lens D0.03cc was observed in MR-Linac plans. Over the course of a patient’s entire radiotherapy regimen, the absolute summed dose difference was <1 Gy for PTV parameters, <1 Gy for brainstem, approximately 3 Gy for each globe, and approximately 2 Gy for each lens. Since MR-Linac treatment plans are adapted to position every fraction , the exact location of these minimally higher dose regions varies geospatially every fraction, which may negate their effects when accumulated over the treatment course. Nonetheless, all MR-Linac treatments achieved standard planning objectives and dose constraints, and it is unlikely that these small differences translate into clinically relevant outcomes.
We also quantitatively characterized the impact of the MR-Linac’s magnetic field on delivered dose to skin and tissue surrounding air cavities. Compared to CBCT-Linac, we observed that MR-Linac treatments showed 1.52 Gy higher Dmean (p<0.0001), and 1.23 Gy higher D2cc (p=0.0007) for tissues surrounding air cavities. Skin D2cc was not statistically different (p>0.05), skin Dmean was 1.10 Gy higher (p<0.0001), and skin V20Gy was 19.04 cm3 higher (p=0.0001) with MR-Linac treatment. This is consistent with recent preliminary studies investigating the effect of the MR-Linac’s magnetic field on radiotherapy treatment [12–17]. Tseng et al. used Monaco to retrospectively generate MR-Linac plans with 9 coplanar non-opposing IMRT beams on 24 patients with intact single brain metastases, and found MR-Linac had 0.08 Gy higher Dmean and 0.6 Gy higher D2cc for skin, and 0.07 Gy higher Dmean and 0.3 Gy higher D2cc for tissues around air cavities . Schrenk et al. used an open-source Monte Carlo-based TPS to retrospectively generate plans in the presence of a magnetic field with ≥7 coplanar non-opposing 3D-CRT and IMRT beams on 4 patients with non-small cell lung cancer, and found that the presence of the perpendicular magnetic field increased mean dose to tissues surrounding the lung air cavity by 0.5 Gy (18.5%) . Nachbar et al. used Monaco to prospectively generate a MR-Linac plan with 7 coplanar non-opposing IMRT beams on 1 breast cancer patient, and found MR-Linac had 0.3 Gy higher D2cc and 15.3% higher V35Gy for skin tissue . Xia et al. used Monaco to retrospectively generate MR-Linac plans with 9 coplanar non-opposing equally spaced IMRT beams on 10 patients with hypopharyngeal cancer, and found MR-Linac had 1.30-1.81 Gy higher Dmean and 1.68-5.43 Gy higher Dmax for skin, and no difference in dose to tissues surrounding air cavities except for higher Dmax to larynx and trachea . Boldrini et al. used MRIdian TPS to retrospectively generate MR-Linac plans with 7 coplanar non-opposing equally-spaced IMRT beams on 10 patients with locally advanced rectal cancer, and found MR-Linac had higher skin dose and higher PTV V105% (14.8%) compared with CBCT-Linac VMAT with two full coplanar arcs (5.0%) and CBCT-Linac IMRT using 5 coplanar beams (7.3%) . Taken together, these studies demonstrated that MR-Linac plans have small increases in dose to skin and tissues surrounding air cavities, and are consistent with our findings. However, the present study is unique in that the selected patient population represents a large cohort of glioma patients who received at least one fraction on both MR-Linac and CBCT-Linac based on clinically approved radiotherapy plans. Second, the plans were prospectively generated prior to treatment and delivered on both MR-Linac and CBCT-Linac, in contrast to previous studies of simulated plans that were retrospectively generated for dosimetric comparison. Lastly and importantly, we performed in vivo measurements to correlate the skin dose calculated on Monaco and Pinnacle, with measured patient skin dose via OSLD on MR-Linac and CBCT-Linac.
A potential limitation of our study is the variability in dose fractionations used. However, plan evaluation was performed with pairwise comparisons between MR-Linac and CBCT-Linac treatments for each patient and are independent of absolute values. Second, there may be potential uncertainty in OSLD measurements caused by placement, air gaps, and surface effects. To mitigate this, a single OSLD measurement was obtained from the same patient’s MR-Linac and CBCT-Linac treatments using standardized technique , although we acknowledge that reproducibility could be assessed by performing additional measurements. Third, since there are differences in how each TPS models patient surface, calculates surface dosimetry, and uses voxel sizes for TPS dose evaluation, we recognize the difficulty in quantifying the magnitude of these effects and their contribution to the dose differences observed. Finally, each patient’s clinically delivered treatment plan was analyzed on the latest version of clinical Monaco TPS, and we acknowledge that future iterations of clinical Monaco may have even better dose optimization, dose engines, and dose modelling.
Potential strategies to mitigate skin dose in MR-Linac treatment include increasing the number of beam angles [21–23], using opposing beam configurations , using VMAT , using partial arcs , using smaller margins on target volumes , and specifically using a skin objective during planning optimization to minimize skin dose. Kim et al. investigated the effects of different beam arrangements on skin dosimetry for partial breast radiotherapy using MR-Linac, and demonstrated an 11-18% increase in skin D1cc and an 146-149% increase in skin V30 with the addition of the magnetic field. However, increasing the number of beam angles, and going from IMRT to VMAT reduced the skin dose in the presence of the magnetic field . Bainbridge et al. investigated the effect of a PTV margin reduction from 7 mm to 3 mm on skin dosimetry for lung cancer radiotherapy using MR-Linac. They demonstrated that MR-Linac plans with 7 mm margins had 0.4 Gy higher Dmean skin dose and 1.7 Gy higher D2cc skin dose compared to CBCT-Linac plans with 7 mm margins. However, MR-Linac plans with a reduced margin (3mm) alleviated this issue, while also decreasing other OAR metrics, and allowed isotoxic dose escalation . In glioblastoma, a phase I/II trial used a reduced 5 mm CTV margin with hypofractionated regimens and demonstrated survival outcomes similar to that of historical control . Therefore, MRI-guided treatment of gliomas with a reduced CTV margin and an adaptive framework not only potentially mitigates skin dose effects on the MR-Linac, but may allow for opportunities to decrease toxicities and incorporate boost strategies based on functional imaging. Finally, since this study demonstrates that Monaco’s Monte Carlo dose algorithm can accurately model the near-surface dose, using the TPS IMRT optimizer with skin as an avoidance structure can reliably decrease skin dose. Additional work to incorporate skin dose mitigation strategies into planning processes are being developed. Future work to prospectively assess dose-related clinical toxicity outcomes, such as wound dehiscence, permanent alopecia, and radiation dermatitis is important. Further studies investigating favorable clinical scenarios where higher dose is required to skin and superficial targets are warranted as well.
In conclusion, this is the first prospective dosimetric comparison of glioma patients clinically treated with at least one fraction on both MR-Linac and CBCT-Linac, combined with in vivo correlation to delivered dose on each platform. The dosimetric impact of the MR-Linac’s magnetic field was minimal for target volumes and standard OARs. However, higher doses to tissues at skin surface and surrounding air cavities were observed for clinically delivered MR-Linac treatments. In vivo correlation of delivered skin dose was more accurately predicted by Monaco. Future MR-Linac planning processes are being designed to account for skin dosimetry and treatment delivery.