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Page 14 of 23 Thonglert et al. Hepatoma Res 2023;9:40 https://dx.doi.org/10.20517/2394-5079.2023.47

The most recent comprehensive study on the clinical outcomes of MRgRT in primary liver cancer was
[70]
conducted at Washington University . The study included 99 patients with unresectable primary liver
cancer (45 with iCCA and 2 with combined HCC-CCA [cHCC/CCA]), who were treated with MRgRT of
50 Gy in 5 fractions. The PTV margin was defined as a 5 mm expansion from the GTV. Online ART was
considered for patients who had tumors situated within 2 cm of luminal GI structures. Among patients with
iCCA or cHCC/CCA, 62% had PTV within 1 cm of the duodenum or small bowel and 53% within 1 cm of
the stomach. 67% of these patients received online ART. The median follow-up duration was 10.1 months
for patients with iCCA or cHCC/CCA, and a 2-year cumulative incidence of local progression was 9.0%
(95%CI: 0.1%-18%). The 1- and 2-year OS rates were 67% (95%CI: 53%-84%) and 31% (95%CI: 17-56),
respectively. Grade ≥ 3 acute and late complications were found in fewer than 10% of the patients.

Regarding clinical application, MRgRT may be more beneficial for iCCA patients whose tumors are located
near GI structures such as the stomach, duodenum, and colon. These organs are relatively radiosensitive
and are at risk of developing late complications such as bleeding, ulceration, and perforations if exposed to
high doses of radiation. Furthermore, they exhibit interfraction variations due to peristalsis and organ
filling. Because MRgRT may be able to address these variations and uncertainties at each delivered fraction,
escalated doses to the tumor can be more safely delivered. Other scenarios that may potentially benefit from
MRgRT include patients with significant motion or those who require fiducial marker implantation but are
unable to undergo the procedure. MRgRT has the potential to provide better soft tissue visualization, real-
time tumor tracking, and gated treatment in these patients [Figure 2].

Challenges and limitations of MRgRT in iCCA
Although MRgRT represents a significant technological advancement in the field of radiotherapy, further
prospective trials are needed to determine its benefits over CT-guided therapy. MRgRT presents challenges
in routine clinical implementation, as treatment requires intensive time and resources. The complex
workflows and extra steps required for online adaptive MRgRT can extend the total treatment time, which
lasts approximately 50-60 mins per adaptive session [60,71] . The process also requires intensive training and
coordination of the multidisciplinary team, including radiation therapists, physicists, dosimetrists, and
physicians [59,60] .

Additionally, substantial investments are required for MRgRT, including upfront costs of the machinery
and equipment, staff training, and the longer treatment duration compared to conventional EBRT with
other types of IGRT . While the treatment cost of MRgRT is higher, there is no data evaluating its cost-
[72]
effectiveness for iCCA patients, especially in relation to its potential efficacy improvement and toxicity
reduction. Thus, this gap necessitates further research.

The presence of various artifacts, such as those related to metal and motion, also poses additional technical
challenges. Motion artifacts can be more challenging for patients who cannot hold their breath. The limited
treatment space in MRI-guided machines may lead to difficulty for large patients, those with lateralized
tumors and individuals experiencing claustrophobia. Furthermore, the physical structure of the machine
restricts the use of multiple beams from different directions, which can potentially reduce the benefit of
OAR sparing. Another limitation is that MR-guided machines can track in only one 2D plane, which may
be insufficient in some case .
[73]

In terms of clinical application, while MRgRT offers improved visualization of the tumor and daily
treatment plan adaptation, it may still not be able to achieve safe dose escalation in some iCCA patients,
such as those with severe cirrhosis or large or multiple tumors. This limitation arises due to MRgRT