Targeted Total Marrow Irradiation Using Three-Dimensional Image-Guided Tomographic Intensity-Modulated Radiation Therapy: An Alternative to Standard Total Body Irradiation

Abstract

Total body irradiation (TBI) is an important part of bone marrow transplantation conditioning regimens. In TBI, dose escalation is difficult, because of associated normal organ toxicities. A method to deliver a more targeted dose of TBI preferentially to sites of greatest tumor burden is needed to reduce the dose to normal organs, reduce toxicities, and permit dose escalation. The purpose of this study was to evaluate, through a dosimetric analysis, the potential advantages and feasibility of selectively delivering targeted myeloablative doses of radiation to bone and marrow using a recently developed image-guided tomographic intensity-modulated radiation therapy delivery system (helical tomotherapy). Whole-body computed tomography datasets from 3 patients, age 5, 20, and 53 years, were used for treatment planning studies to evaluate 2 targeted TBI strategies: total marrow irradiation (TMI), in which the target region was defined as the skeletal bone, and total marrow and lymphoid irradiation (TMLI), in which the target regions were defined as bone, major lymph node chains, liver, spleen, and sanctuary sites, such as brain. Organ doses and dose distributions were compared with those in conventional TBI. A 1.7- to 7.5-fold reduction in median organ doses was observed with TMI and TMLI compared with conventional TBI. With this more targeted approach, a dose-volume histogram analysis predicted the potential to escalate the dose to bone (and containing marrow) up to 20 Gy, while maintaining doses to normal organs at lower levels than in conventional TBI to 12 Gy. Results were similar for the adult and pediatric patients, indicating that this form of targeted TBI will be applicable to most patients regardless of frame size. TMI to 10 Gy was delivered as part of a tandem transplant regimen to the 53-year-old patient with multiple myeloma. Clinical results confirmed the treatment planning predictions. After TMI, the patient experienced the expected blood count nadir, followed by successful engraftment. Grade 2 nausea and grade 1 emesis occurred only briefly on day 2 of TMI. Skin erythema, oral mucositis, esophagitis, and enteritis were not observed. This report demonstrates the feasibility and potential dosimetric advantages of selectively delivering myeloablative doses of radiation to bone and marrow using an image-guided tomographic intensity-modulated radiation therapy delivery system. Organ doses are substantially lower than those associated with standard TBI and predict the potential to significantly reduce associated toxicities and allow for dose escalation. The results also suggest that this form of targeted TBI may have potential advantages over other forms of targeted TBI, such as radioimmunotherapy or bone-seeking radionuclide therapy. Ongoing clinical trials will define the maximum TMI and TMLI doses achievable and define the potential advantages and limitations of this new approach for patients undergoing hematopoietic stem cell transplantation.

TBI during BM and SCT: review of the past, discussion of the present and consideration of future directions

“…Total marrow irradiation using helical tomography was delivered to one patient, who experienced a blood count nadir followed by successful engraftment, accompanied by limited nausea and vomiting, and no erythema, oral mucositis or esophagitis. 73 Certainly, these preliminary studies support further investigation into clinical feasibility of use of helical tomotherapy for delivery of TBI with sparing of critical normal structures. This technique may allow delivery of myeloablative doses to a broader range of patients if toxicity to normal critical structures can be limited clinically (Table 3).…”

“…72 Treatment planning time did not appear to differ significantly between the two techniques, although treatment delivery took a longer period of time when tomotherapy was employed. Wong et al 73 performed a similar study evaluating use of tomotherapy to treat the total marrow (target region skeletal bone) as well as the major lymph node chains, spleen and sanctuary sites. They demonstrated a 1.7-7.5-fold reduction in median organ dose with these techniques compared with conventional TBI.…”

Energy‐dependent OAR sparing and dose conformity for total marrow irradiation of obese patients

“…All treatment plans to date have used a beam energy of 6 MV, however, the retrospective planning study presented in this manuscript aims to investigate the effects of using a 10 MV beam for TMI VMAT fields in comparison to 6 MV. High energy beams (10–18 MV) have historically been a part of TBI treatments, particularly for patients of thickness greater than 35 cm;3, 22 however, published experience with modulated TMI fields has been limited to 6 MV IMRT and VMAT or helical tomotherapy 14, 15, 23, 24, 25, 26, 27, 28. Potential disadvantages of increasing beam energy include larger penumbra and the production of secondary neutrons originating in the head of the linac.…”

A Clinical Dosimetry Analysis of Total Body Irradiation for Leukemia Patients

“…Nowadays the majority of clinics still use the conventional TBI techniques mentioned above except for a few trials [4][5][6], which simply apply AP and PA fields without using Multileaf Collimator (MLC) to modulate the beams delivering prescribed doses to different body parts. 3D treatment plan technique is also not used for the treatments, which means that the detail dose distributions are not available for evaluating the treatments.…”