2289 - A Dose Escalation Planning Study Using Total Marrow and Lymphoid Irradiation in a Reduced-Intensity Conditioning Regimen

Purpose/Objective(s): Total body irradiation is performed as a conditioning regimen for allogeneic hematopoietic stem cell transplantations. Reduced-intensity conditioning (RIC) is used for elderly patients unable to tolerate myeloablative conditioning (MAC) or patients with organ dysfunction but has limited antitumor efficacy. The present planning study with total marrow and lymphoid irradiation (TMLI) evaluated the potential for increasing the dose using intensity-modulated radiation therapy on the hypothesis that this method can deliver a higher dose to the target while minimizing exposure to organs at risk (OARs) in an RIC regimen.

Materials/Methods: Planning CT of five patients who received TMLI therapy with treatment delivery system between December 2023 and July 2024 were used. Five plans were created per patient using a treatment planning system with prescribed doses of 4 Gy/2 fr, 5 Gy/2 fr, 8 Gy/4 fr, 9 Gy/3 fr, and 10 Gy/4 fr. The planning target volume (PTV) included the bone marrow, lymph nodal region, testes, and spleen with D80% as the prescribed dose. The brain and liver were also targeted; however, for plans = 3 fr, the D80% of the prescribed dose was set at physical 5 Gy to ensure biologically equivalent to 4 Gy/2 fr. The PTV homogeneity index (HI) was calculated using the formula in ICRU Report 83. The OARs included the lenses, oral cavity, parotid glands, lungs, heart, esophagus, stomach, kidneys, intestines, and breasts (for women). The mean physical dose to OARs other than the stomach and breasts was < 4 Gy for 2 fr and < 5 Gy for = 3 fr. Dose constraints were also applied to ensure that the Dmax, D2%, and D10% of all OARs remained below the prescribed dose.

Results: The table shows the HI of the PTV and the Dmean for the lungs, kidneys, and oral cavity. All the plans achieved D80% of the PTV at the prescribed dose. D80% of the brain and liver was also achieved at 4 or 5 Gy. The HI increased significantly at doses above 9 Gy (?0.25), reaching a maximum value at 10 Gy/4 fr with decreased uniformity. The Dmean for all OARs increased with an escalation in the prescribed dose, but all the plans satisfied the dose constraints.

Conclusion: The TMLI technique in the RIC regimen enables the target dose to be escalated to 10 Gy/4 fr, the equivalent of the MAC regimen, while keeping the dose to the OARs constant. It should be noted that increasing the dose reduces target homogeneity. Table. Median value of the HI for the PTV and the Dmean for the lungs, kidneys, and oral cavity at each prescription dose