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Purpose: Total marrow irradiation (TMI) is a highly conformal treatment of the human skeleton structure requiring a high degree of precision and accuracy for treatment delivery. Although many centers worldwide initiated clinical studies using TMI, currently there is no standard for pretreatment patient setup. To this end, the accuracy of different patient setups was measured using pretreatment imaging. Their impact on dose delivery was assessed for multiple institutions., Methods and Materials: Whole body imaging (WBI) or partial body imaging (PBI) was performed using pretreatment megavoltage computed tomography (MVCT) in a helical Tomotherapy machine. Rigid registration of MVCT and planning kilovoltage computed tomography images were performed to measure setup error and its effect on dose distribution. The entire skeleton was considered the planning target volume (PTV) with five sub regions: head/neck (HN), spine, shoulder and clavicle (SC), and one avoidance structure, the lungs. Sixty-eight total patients (>300 images) across six institutions were analyzed., Results: Patient setup techniques differed between centers, creating variations in dose delivery. Registration accuracy varied by anatomical region and by imaging technique, with the lowest to the highest degree of pretreatment rigid shifts in the following order: spine, pelvis, HN, SC, and lungs. Mean fractional dose was affected in regions of high registration mismatch, in particular the lungs., Conclusions: MVCT imaging and whole body patient immobilization was essential for assessing treatment setup, allowing for the complete analysis of 3D dose distribution in the PTV and lungs (or avoidance structures)., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Purpose: Normal organ toxicity is the leading factor that limits dose escalation in total body irradiation for bone marrow transplant (BMT) patients. In recent years, total marrow irradiation (TMI) using the helical tomotherapy (HT) system is being used as a more targeted form of TBI to treat BMT patients. In this study, we evaluated the feasibility of using volumetric modulated arc therapy (VMAT) to deliver TMI treatment., Materials and Methods: CT data sets from two female and two male patients who had received prior total marrow and lymphatic irradiation with HT were selected for this study. The target volumes included skeletal bones from the skull to the mid-thigh level, major lymph nodes, and spleen. Twelve Gray in 8 fractions was prescribed to the target volumes. Each VMAT plan was generated with eight arc fields to cover the entire target volumes. Both the VMAT and the HT plans were normalized so that 85% of the skeletal bone volume was covered by the prescription dose. For each patient, more than 20 normal organs were included in plan optimization., Results: Both the VMAT and HT plans showed comparable dose coverage to the target volumes and significant sparing of normal organ dose. The median dose to the skeletal bone volume was 13.4 and 12.6 Gy in the VMAT and HT plans, respectively. The VMAT plans showed >10% and >20% reduction of average median dose compared to the HT plans in 16 and 11 organs, respectively. The average beam-on time was 628±32 s and 1122±106 s in the VMAT and HT plans, respectively., Conclusions: The VMAT plans provided adequate target dose coverage and normal organ sparing compared to helical tomotherapy plans for efficient delivery of total marrow and lymphatic irradiation. This study demonstrates that the VMAT technique could be a feasible alternative to helical tomotherapy for TMI treatment., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: TMI utilizes IMRT to deliver organ sparing targeted radiotherapy in patients undergoing hematopoietic cell transplantation (HCT). TMI addresses an unmet need, specifically patients with refractory or relapsed (R/R) hematologic malignancies who have poor outcomes with standard HCT regimens and where attempts to improve outcomes by adding or dose escalating TBI are not possible due to increased toxicities. Over 500 patients have received TMI at this center. This review summarizes this experience including planning and delivery, clinical results, and future directions. Methods: Patients were treated on prospective allogeneic HCT trials using helical tomographic or VMAT IMRT delivery. Target structures included the bone/marrow only (TMI), or the addition of lymph nodes, and spleen (total marrow and lymphoid irradiation, TMLI). Total dose ranged from 12 to 20 Gy at 1.5-2.0 Gy fractions twice daily. Results: Trials demonstrate engraftment in all patients and a low incidence of radiation related toxicities and extramedullary relapses. In R/R acute leukemia TMLI 20 Gy, etoposide, and cyclophosphamide (Cy) results in a 1-year non- relapse mortality (NRM) rate of 6% and 2-year overall survival (OS) of 48%; TMLI 12 Gy added to fludarabine (flu) and melphalan (mel) in older patients (≥ 60 years old) results in a NRM rate of 33% comparable to flu/mel alone, and 5-year OS of 42%; and TMLI 20 Gy/flu/Cy and post-transplant Cy (PTCy) in haplo- identical HCT results in a 2-year NRM rate of 13% and 1-year OS of 83%. In AML in complete remission, TMLI 20 Gy and PTCy results in 2-year NRM, OS, and GVHD free/relapse-free survival (GRFS) rates of 0%, 86•7%, and 59.3%, respectively. Conclusion: TMI/TMLI shows significant promise, low NRM rates, the ability to offer myeloablative radiation containing regimens to older patients, the ability to dose escalate, and response and survival rates that compare favorably to published results. Collaboration between radiation oncology and hematology is key to successful implementation. TMI/TMLI represents a paradigmshift from TBI towards novel strategies to integrate a safer and more effective target-specific radiation therapy into HCT conditioning beyond what is possible with TBI and will help expand and redefine the role of radiotherapy in HCT. [ABSTRACT FROM AUTHOR]

Purpose: Toxicities after organ sparing myeloablative total marrow irradiation (TMI) conditioning regimens have not been well characterized. The purpose of this study is to report pulmonary, renal, thyroid, and cataract toxicities from a prospective trial monitoring patients up to 8 years after TMI.Methods and Materials: A total of 142 patients with primarily multiple myeloma or acute leukemia undergoing hematopoietic cell transplantation were evaluated. Follow-up included pulmonary function tests, serum creatinine, glomerular filtration rate, thyroid panel, and ophthalmologic examinations performed at 100 days, 6 months, and annually. Median TMI dose was 14 Gy (10-19 Gy) delivered at 1.5 to 2.0 Gy twice per day at a dose-rate of 200 cGy/min.Results: Median age was 52 years (range 9-70). Median follow-up (range) for all patients was 2 years (0-8) and for patients alive at the time of last follow-up (n = 50), 5.5 years (0-8). Mean organ doses in Gy were lung 7.0, kidneys 7.1, thyroid 6.7, and lens 2.8. The crude incidence of radiation pneumonitis (RP) was 1 of 142 (0.7%). The cumulative incidence of infection and RP (I/RP) was 22.7% at 2 years post-TMI. Mean lung dose ≤8 Gy predicted for significantly lower rates of I/RP (2-year cumulative incidence 20.8% vs 31.8%, P = .012). No radiation-induced renal toxicity was noted. Hypothyroidism occurred in 6.0% and cataract formation in 7.0% of patients.Conclusions: TMI delivered with intensity modulated radiation therapy results in lower organ doses and was associated with fewer toxicities compared with historical cohorts treated with conventional total body irradiation. Keeping the mean lung dose to 8 Gy or less was associated with lower pulmonary complications. Further evaluation in clinical trials of intensity modulated radiation therapy to deliver TMI, total marrow and lymphoid irradiation, and organ sparing conformal total body irradiation is warranted. [ABSTRACT FROM AUTHOR]