To the best of our knowledge, this is the first case series of patients with both MDS/MPN and MFI who have undergone SI with MRgRT performed with the MR Linac using both the online and offline adaptive approach.
Adaptive radiation treatment planning, was employed to account for changes in splenic size during treatment. The use of real-time setup verification through MR scans and direct gating of the target during delivery allowed for the implementation of tailored and narrower GTV-PTV treatment margins, ranging from 3 to 5 mm in all directions, based on the chosen gating phase (BHI or FB) on a case-by-case basis, in order to reduce exposure to healthy tissues. Furthermore, the application of adaptive RT protocols enabled adjustments to the treatment plan in response to changes in splenic size throughout the RT course, thereby preventing unnecessary irradiation of healthy tissues on treatment days.
In addition, dose conformality was improved even in the presence of targets with very voluminous cranio-caudal extensions by using the double isocentre irradiation technique to overcome the limited field size of the MR linac (Placidi et al. 2021a).
An adaptive CT-based RT study was performed by Sager et al (Sager et al. 2015), who retrospectively included 18 patients with splenomegaly, 12 of whom were MFI. The authors demonstrated the feasibility of a reduction in GTV-PTV margins, based on the study of spleen movement.
Considering the clinical outcomes, in our case series we had 100% reduction in spleen volume. This finding is very interesting when compared with the most recent data in the literature, which range from 62% (Katano et al. 2021) to 81.8% (Sager et al. 2015), with 72% reported in a meta-analysis by Zaorsky et al (Zaorsky et al. 2017), although the case series include patients with splenomegaly caused by various medical conditions.
Regarding the extent of reduction, Sager et al (Sager et al. 2015) and Katano et al (Katano et al. 2021) observed a reduction in spleen size of 50% and a mean ± SD variation rate in spleen volume of -19.1 ± 24.7%, respectively. Furthermore, Ponce et al (Ponce et al. 2022), in a study of 17 patients, including 14 with MFI, who underwent SI followed by HCT, reported a median craniocaudal reduction in spleen size of 7.3%.
In the present work, the mean percentage change in volume and cranio-caudal extension between simulation and final RT fraction was 53.61% and 77.78%, respectively, therefore our result can be considered very favourable.
In terms of pain relief and associated gastrointestinal symptoms, pain improved in all 5 (100%) patients who reported it before treatment. Gastrointestinal symptoms remained stable in 5 (50%) patients and improved in 3 (30%) patients. Referring to the case histories mentioned above, the palliation rates of pain and other symptoms associated with splenic bulk range from 60% (Katano et al. 2021) to 90.9% (Sager et al. 2015).
In addition, the treatment was well tolerated by patients, with none reporting any level of non-haematological toxicity. At the same time, transfusion support, when deemed indicated, allowed treatment to be completed without interruption in all cases.
Although it is clearly not possible to draw conclusions on the benefit of SI as part of HCT conditioning from a long-term survival outcome perspective due to the retrospective nature of the present study and the small number of patients included, with 75% of patients receiving HCT, this study provides further evidence of the feasibility of this approach in patients with pMFI, sMFI and MDS/MPN (Ponce et al. 2022).
We believe that this study can contribute valuable evidence to the current body of literature, which predominantly relies on outdated RT techniques.
MRgRT has emerged as a transformative technology in the field of radiation oncology, offering unique advantages across diverse clinical scenarios, as stereotactic body radiation therapy (SBRT) for lung, liver and pancreatic tumors, where the ability to track and adapt to tumor motion ensures optimal treatment delivery (Placidi et al. 2020; Boldrini et al. 2021b, c; Chiloiro et al. 2023; Sandoval et al. 2023). MRgRT's application also extends to challenging applications, such as the irradiation of peritoneal nodules and of cardiac tumors (Boldrini et al. 2020; Corradini et al. 2021).
In the field of hematological malignancies, as demonstrated in our study, MRgRT offers promise in managing splenomegaly, providing rapid symptom relief and substantial spleen volume reduction.
As interesting as this treatment approach is, its retrospective nature, small sample size and consequently the lack of detailed statistical analysis should be considered when interpreting the results.
Other limitations to be considered are the heterogeneous population included in the study, which may make it difficult to draw specific conclusions on treatment efficacy for each subgroup, and the short follow-up period, especially in patients undergoing HCT, may not give full information on long-term survival outcomes, which are crucial in assessing treatment efficacy.
Furthermore, the absence of a comparison group and comprehensive clinical endpoints warrants cautious interpretation of the results.
Additional research with larger sample sizes, longer follow-up periods, and more comprehensive outcome measures is needed to better understand the potential benefits and limitations of this treatment approach.