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Abstract
I read with great interest the article by Köksal et al. entitled “Total marrow irradiation versus total body irradiation using intensity-modulated tomotherapy” (Journal of helical Cancer Research and Clinical Oncology, 2023;149:5965–5973)(1). The authors should be commended for addressing an important and practical question in transplant conditioning radiotherapy: whether total marrow irradiation (TMI) can reduce organ-at-risk (OAR) exposure compared with total body irradiation (TBI) while maintaining target dose coverage, using a within-patient planning comparison to minimize interpatient confounding. The study’s key message clinically meaningful OAR sparing with TMI planning aligns with the underlying rationale of marrow-focused irradiation.
In their cohort of 35 patients, the authors report substantial reductions in mean dose to several critical organs (notably liver and spleen by ~49%, kidneys by ~55–59%) while preserving skeletal target coverage, with a significant improvement in D98 for the skeleton (p=0.001). Such findings reinforce prior feasibility and dose-escalation experiences suggesting that improved conformality may enable intensified conditioning while mitigating toxicity constraints (2, 3). Additionally, their observation that TMI reduced corpus beam-on time despite a higher modulation factor is practically relevant for workflow and patient tolerability. We would like to offer several points for consideration that may help interpret and extend the work. First, the retrospective “theoretical plan” design is a strength for paired dosimetric comparison; however, it also limits inference about clinical outcomes (e.g., pulmonary, renal, hepatic toxicities; engraftment; GVHD; relapse patterns).
While the authors appropriately cite clinical data supporting organ-sparing 11 strategies with total marrow approaches(4) ,prospective correlations between dosimetry (e.g., kidney/liver mean dose reductions) and toxicity endpoints would be valuable. A pragmatic next step could be to predefine organ-specific dose constraints and evaluate how frequently TMI enables constraint satisfaction at 12–15 Gy conditioning in real-world delivery. Second, the reported increase in eye/lens doses with TMI planning though not statistically accompanied deserves by significant high and variability attention. Given
the radiosensitivity of the lens and the potential for cataractogenesis, it would be helpful to understand whether this reflects differences in contouring, planning priorities, or constraints used during optimization. Incorporating standardized ocular constraints, or reporting additional dose–volume metrics (e.g., lens Dmax or D0.03cc), could clarify whether this is clinically meaningful. Third, the authors highlight the planning workload (approximately 4 hours per patient for whole-skeleton contouring including distal extremities). This is an important adoption barrier. As they note, atlas-based and deep learning auto segmentation tools can reduce variability and workload (3). It would be informative in future reports to quantify (a) auto contour editing time, (b) contour accuracy measures (e.g., DSC/HD), and (c) the downstream impact on dosimetry, particularly at challenging sites such as ribs, sternum, hands, and feet. Fourth, with respect to lung sparing, the discussion appropriately notes that conventional shielding/blocks may underdose ribs/sternum and potentially relate to relapse risk (5, 6). Given the study’s DVH illustration showing more consistent lung sparing with TMI, a nuanced analysis of skeletal subregions (e.g., thoracic cage, sternum) and their coverage could further strengthen the argument for TMI over TBI when lung blocks are used. Reporting subregion target metrics might also help address concerns about extramedullary relapse, even though prior work suggests comparable extramedullary relapse rates between approaches (7).
Finally, the beam-on time analysis, restricted to the subset with available TBI times (n=19), is useful, but total treatment time is also influenced by imaging and setup. Incorporating alternative positioning/alignment workflows (e.g., optical surface guidance for legs) as described by Haraldsson et al. may provide a more comprehensive view of patient throughput and feasibility (4). In conclusion, Köksal et al. provide a careful
dosimetric comparison suggesting that TMI with helical tomotherapy can substantially reduce OAR doses while maintaining skeletal target coverage, and may offer workflow advantages for the corpus component. We believe their work supports broader evaluation of TMI within conditioning regimens, ideally with prospective toxicity and outcomes data and standardized planning/contouring pipelines. Sincerely,
