Favorable outcomes and low toxicity of total body irradiation (TBI) using intensity modulated radiation therapy (IMRT) for normal organ sparing prior to hematopoietic stem cell transplantation

Summary: Total body irradiation (TBI) is used as a myeloablative conditioning regimen in patients with hematologic or lymphoid malignancies prior to allogeneic hematopoietic stem cell transplant (HSCT). TBI can be associated with multi-organ toxicity. Traditional techniques, such as the use of shielding blocks, provide some protection to the lungs but do not significantly reduce the dose to other vital organs. We describe utilization of an organ-sparing volumetric modulated arc therapy (VMAT) technique in three patients and report patient outcomes. Three patients were treated on an Elekta Agility® linear accelerator (Elekta AB, Stockholm, Sweden) using RayStation treatment planning software (RaySearch Laboratories, Stockholm, Sweden). A 5mm robustness margin was utilized to account for setup error and internal organ motion, introducing a feathering effect. All patients were female and ranged in age from 37 to 75 years at the time of TBI. Patient 1 (ALL) was treated with 12 Gy in 6 fractions (2 Gy twice daily on days 2 and 3, 2 Gy once on days 1 and 4), while patients 2 (AML) and 3 (ALCL) were treated with a single 2 Gy fraction. Patient 3 was also treated with a single 8 Gy fraction to residual neck disease at the time of TBI. All patient plans were optimized to deliver no more than 58% of the prescription dose to the organs at risk (OARs) including the lungs, eyes, oral cavity, heart, and kidneys. Patients were first treated feet-first supine with 3 isocenters, then rotated and treated head-first supine with an additional 3 isocenters. Cone-beam CT imaging was used for every isocenter and any necessary shifts were applied to each isocenter. With follow-up for patients 1, 2, and 3 of 12 months, 6 months, and 3 months, respectively, all patients had normal pulmonary function tests. None had gastrointestinal or pulmonary symptoms, B symptoms, or graft-versus-host-disease (GVHD). At last follow up, patients 1 and 2 had no evidence of disease progression, while patient 3, who had residual neck disease at the time of TBI, had local disease progression. Using this VMAT technique with a 5mm robustness margin we were able to decrease the radiation dose to organs at risk by 42%. At follow-up, none of the patients had radiation side effects, and two of the three patients remain without evidence of disease. In the remaining patient, progression was at the site of bulky disease present at the time of treatment and not in a protected organ. Our approach allows target doses to be easily customized and OAR constraints to be adjusted according to the clinical situation and emerging data. Our technique reduces the radiation dose to critical organs, with the goal of reducing toxicity without sacrificing efficacy. Kiersten L. Berggren (she/her/hers), PhD (Presenting Author) - University of New Mexico; Patricia Sansourekidou (she/her/hers), PhD (Co-Author) - University of New Mexico Comprehensive Cancer Center; David Y. Lee (he/him/his), MD, PhD (Co-Author) - University of New Mexico Comprehensive Cancer Center; Ben Liem (he/him/his), MD (Co-Author) - University of New Mexico Comprehensive Cancer Center; Matthew Fero (he/him/his), MD (Co-Author) - University of New Mexico Comprehensive Cancer Center; Charles Foucar (he/him/his), MD (Co-Author) - University of New Mexico Comprehensive Cancer Center; Ramesh Gopal (he/him/his), MD, PhD (Co-Author) - University of New Mexico Comprehensive Cancer Center