Editorial: Total marrow irradiation.
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ABSTRACT:
SUBMITTER: Hui SK
PROVIDER: S-EPMC10395326 | biostudies-literature | 2023
REPOSITORIES: biostudies-literature
Publications
Editorial: Total marrow irradiation.
Hui Susanta Kumar SK Storme Guy G Wong Jeffrey J Aristei Cynthia C Al Malki Monzr M MM Aydogan Bulent B
Frontiers in oncology 20230719
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Project description:BackgroundTotal body irradiation (TBI) is often a component of the conditioning regimen prior to hematopoietic stem cell transplantation in patients with hematological malignancies. However, total marrow irradiation (TMI) could be an alternative method for reducing radiation therapy-associated toxicity, as it specifically targets the skeleton and thus could better protect organs at risk. Here, we compared dosimetric changes in irradiation received by the target volume and organs at risk between TBI and TMI plans.Materials and methodsTheoretical TMI plans were calculated for 35 patients with various hematological malignancies who had already received TBI in our clinic. We then statistically compared irradiation doses between the new TMI plans and existing TBI plans. We examined whether TMI provides greater protection of organs at risk while maintaining the prescribed dose in the targeted skeletal area. We also compared beam-on times between TBI and TMI.ResultsTMI planning achieved significant reductions in the mean, minimum, and maximum irradiation doses in the lungs, kidneys, liver, spleen, and body (i.e., remaining tissue except organs and skeleton). In particular, the mean dose was reduced by 49% in the liver and spleen and by 55-59% in the kidneys. Moreover, TMI planning reduced the corpus beam-on time by an average of 217 s.ConclusionTMI planning achieved significant dose reduction in organs at risk while still achieving the prescribed dose in the target volume. Additionally, TMI planning reduced the beam-on time for corpus plans despite a high modulation factor.
| S-EPMC10356893 | biostudies-literature
Project description:PurposeTargeted marrow irradiation (TMI) is an alternative conditioning regimen to total body irradiation (TBI) before bone marrow transplantation in hematologic malignancies. Intensity-modulation methods of external beam radiation therapy are intended to permit significant organ sparing while maintaining adequate target coverage, improving the therapeutic ratio. This study directly compares the dose distributions to targets and organs at risk from TMI and TBI, both modalities conducted by general-use medical linacs at our institution.MethodsTMI treatments were planned for 10 patients using multi-isocentric feathered volumetric arc therapy (VMAT) plans, delivered by 6 MV photon beams of Elekta Synergy linacs. The computed tomography (CT) datasets used to obtain these plans were also used to generate dose distributions of TBI treatments given in the AP/PA extended-field method. We compared dose distributions normalized to the same prescription for both plan types. The generalized equivalent uniform dose (gEUD) of Niemierko for organs and target volumes was used to quantify effective whole structure dose and dose savings.ResultsFor the clinical target volume (CTV), no significant differences were found in mean dose or gEUD, although the radical dose homogeneity index (minimum dose divided by maximum dose) was 31.7% lower (P = 0.002) and the standard deviation of dose was 28.0% greater (P = 0.027) in the TMI plans than in the TBI plans. For the TMI plans, gEUD to the lungs, brain, kidneys, and liver was significantly lower (P < 0.001) by 47.8%, 33.3%, 55.4%, and 51.0%, respectively.ConclusionTMI is capable of maintaining CTV coverage as compared to that achieved in TBI, while significantly sparing organs at risk. Improvement on sparing organs at risk permits a higher prescribed dose to the target or the maximum number of times marrow conditioning may be delivered to a patient while maintaining similar typical tissue complication rates.
| S-EPMC6839384 | biostudies-literature
Project description:PurposeTo develop a murine total marrow irradiation (TMI) model in comparison with the total body irradiation (TBI) model.Materials and methodsMyeloablative TMI and TBI were administered in mice using a custom jig, and the dosimetric differences between TBI and TMI were evaluated. The early effects of TBI/TMI on bone marrow (BM) and organs were evaluated using histology, FDG-PET, and cytokine production. TMI and TBI with and without cyclophosphamide (Cy) were evaluated for donor cell engraftment and tissue damage early after allogeneic hematopoietic cell transplantation (HCT). Stromal derived factor-1 (SDF-1) expression was evaluated.ResultsTMI resulted in similar dose exposure to bone and 50% reduction in dose to bystander organs. BM histology was similar between the groups. In the non-HCT model, TMI mice had significantly less acute intestinal and lung injury compared to TBI. In the HCT model, recipients of TMI had significantly less acute intestinal injury and spleen GVHD, but increased early donor cell engraftment and BM:organ SDF-1 ratio compared to TBI recipients.ConclusionsThe expected BM damage was similar in both models, but the damage to other normal tissues was reduced by TMI. However, BM engraftment was improved in the TMI group compared to TBI, which may be due to enhanced production of SDF-1 in BM relative to other organs after TMI.
| S-EPMC5624834 | biostudies-literature
Project description:PurposeTotal marrow irradiation (TMI) involves optimization of extremely large target volumes and requires extensive clinical experience and time for both treatment planning and delivery. Although volumetric modulated arc therapy (VMAT) achieves substantial reduction in treatment delivery time, planning process still presents a challenge due to use of multiple isocenters and multiple overlapping arcs. We developed and evaluated a knowledge-based planning (KBP) model for VMAT-TMI to address these clinical challenges.MethodsFifty-one patients previously treated in our clinic were selected for the model training, while 22 patients from another clinic were used as a test set. All plans used a 3-isocenter to cover sub-target volumes of head and neck (HN), chest, and pelvis. Chest plan was performed first and then used as the base dose for both the HN and pelvis plans to reduce hot spots around the field junctions. This resulted in a wide range of dose-volume histograms (DVH). To address this, plans without the base-dose plan were optimized and added to the library to train the model.ResultsKBP achieved our clinical goals (95% of PTV receives 100% of Rx) in a single day, which used to take 4-6 days of effort without KBP. Statistically significant reductions with KBP were observed in the mean dose values to brain, lungs, oral cavity and lenses. KBP substantially improved 105% dose spillage (14.1% ± 2.4% vs 31.8% ± 3.8%), conformity index (1.51 ± 0.06 vs 1.81 ± 0.12) and homogeneity index (1.25 ± 0.02 vs 1.33 ± 0.03).ConclusionsKBP improved dosimetric performance with uniform quality. It reduced dependence on planner experience and achieved a factor of 5 reduction in planning time to produce quality plans to allow its wide-spread clinical implementation.
| S-EPMC9577613 | biostudies-literature
Project description:PurposeTotal marrow irradiation (TMI) has significantly advanced radiation conditioning for hematopoietic cell transplantation in hematologic malignancies by reducing conditioning-induced toxicities and improving survival outcomes in relapsed/refractory patients. However, the relapse rate remains high, and the lack of a preclinical TMI model has hindered scientific advancements. To accelerate TMI translation to the clinic, we developed a TMI delivery system in preclinical models.Methods and materialsA Precision X-RAD SmART irradiator was used for TMI model development. Images acquired with whole-body contrast-enhanced computed tomography (CT) were used to reconstruct and delineate targets and vital organs for each mouse. Multiple beam and CT-guided Monte Carlo-based plans were performed to optimize doses to the targets and to vary doses to the vital organs. Long-term engraftment and reconstitution potential were evaluated by a congenic bone marrow transplantation (BMT) model and serial secondary BMT, respectively. Donor cell engraftment was measured using noninvasive bioluminescence imaging and flow cytometry.ResultsMultimodal imaging enabled identification of targets (skeleton and spleen) and vital organs (eg, lungs, gut, liver). In contrast to total body irradiation (TBI), TMI treatment allowed variation of radiation dose exposure to organs relative to the target dose. Dose reduction mirrored that in clinical TMI studies. Similar to TBI, mice treated with different TMI regimens showed full long-term donor engraftment in primary BMT and second serial BMT. The TBI-treated mice showed acute gut damage, which was minimized in mice treated with TMI.ConclusionsA novel multimodal image guided preclinical TMI model is reported here. TMI conditioning maintained long-term engraftment with reconstitution potential and reduced organ damage. Therefore, this TMI model provides a unique opportunity to study the therapeutic benefit of reduced organ damage and BM dose escalation to optimize treatment regimens in BMT and hematologic malignancies.
| S-EPMC8565655 | biostudies-literature
Project description:PurposeTo develop, characterize, and implement a fast patient localization method for total marrow irradiation.Methods and materialsTopographic images were acquired using megavoltage computed tomography (MVCT) detector data by delivering static orthogonal beams while the couch traversed through the gantry. Geometric and detector response corrections were performed to generate a megavoltage topogram (MVtopo). We also generated kilovoltage topograms (kVtopo) from the projection data of 3-dimensional CT images to reproduce the same geometry as helical tomotherapy. The MVtopo imaging dose and the optimal image acquisition parameters were investigated. A multi-institutional phantom study was performed to verify the image registration uncertainty. Forty-five MVtopo images were acquired and analyzed with in-house image registration software.ResultsThe smallest jaw size (front and backup jaws of 0) provided the best image contrast and longitudinal resolution. Couch velocity did not affect the image quality or geometric accuracy. The MVtopo dose was less than the MVCT dose. The image registration uncertainty from the multi-institutional study was within 2.8 mm. In patient localization, the differences in calculated couch shift between the registration with MVtopo-kVtopo and MVCT-kVCT images in lateral, cranial-caudal, and vertical directions were 2.2 ± 1.7 mm, 2.6 ± 1.4 mm, and 2.7 ± 1.1 mm, respectively. The imaging time in MVtopo acquisition at the couch speed of 3 cm/s was <1 minute, compared with ≥15 minutes in MVCT for all patients.ConclusionWhole-body MVtopo imaging could be an effective alternative to time-consuming MVCT for total marrow irradiation patient localization.
| S-EPMC4385424 | biostudies-literature
Project description:PurposeThe goal of this study is to investigate treatment planning of total marrow irradiation (TMI) using intensity-modulated spot-scanning proton therapy (IMPT). The dosimetric parameters of the intensity-modulated proton plans were evaluated and compared with the corresponding TMI plans generated with volumetric modulated arc therapy (VMAT) using photon beams.MethodsIntensity-modulated proton plans for TMI were created using the Monte Carlo dose-calculation algorithm in the Raystation 11A treatment planning system with spot-scanning proton beams from the MEVION S250i Hyperscan system. Treatment plans were generated with four isocenters placed along the longitudinal direction, each with a set of five beams for a total of 20 beams. VMAT-TMI plans were generated with the Eclipse-V15 analytical anisotropic algorithm (AAA) using a Varian Trilogy machine. Three planning target volumes (PTVs) for the bones, ribs, and spleen were covered by 12 Gy. The dose conformity index, D80, D50, and D10, for PTVs and organs at risk (OARs) for the IMPT plans were quantified and compared with the corresponding VMAT plans.ResultsThe mean dose for most of the OARs was reduced substantially (5% and more) in the IMPT plans for TMI in comparison with VMAT plans except for the esophagus and thyroid, which experienced an increase in dose. This dose reduction is due to the fast dose falloff of the distal Bragg peak in the proton plans. The conformity index was found to be similar (0.78 vs 0.75) for the photon and proton plans. IMPT plans provided superior superficial dose coverage for the skull and ribs in comparison with VMAT because of increased entrance dose deposition by the proton beams.ConclusionTreatment plans for TMI generated with IMPT were superior to VMAT plans mainly due to a large reduction in the OAR dose. Although the current IMPT-TMI technique is not clinically practical due to the long overall treatment time, this study presents an enticing alternative to conventional TMI with photons by providing superior dose coverage of the targets, increased sparing of the OARs, and enhanced radiobiological effects associated with proton therapy.
| S-EPMC9365973 | biostudies-literature
Project description:Posttransplant cyclophosphamide (PTCy) platform has shown low rates of graft-versus-host disease (GVHD) and nonrelapse mortality (NRM) after haploidentical hematopoietic cell transplantation (HaploHCT). However, because of the limited disease control, relapse rate remains a major cause of treatment failure in high-risk patients. Total marrow and lymphoid irradiation (TMLI) allows for delivery of high radiation to bone marrow and other targeted structures, without increasing off-target radiation exposure and toxicity to end organs. In this phase 1 trial, 31 patients with high-risk and/or active primary refractory leukemias or myelodysplastic syndrome underwent peripheral blood stem cell HaploHCT with TMLI, fludarabine, and cyclophosphamide as the conditioning regimen. Radiation dose was escalated in increments of 200 cGy (1200-2000 cGy). GVHD prophylaxis was PTCy with tacrolimus/mycophenolate mofetil. Grade 2 toxicities by the Bearman scale were mucositis (n = 1), hepatic (n = 3), gastrointestinal (n = 5), and cardiac (n = 2). One patient (1800 cGy) experienced grade 3 pulmonary toxicity (dose-limiting toxicity). At a follow-up duration of 23.9 months for the whole cohort; 2-year NRM was 13%. Cumulative incidence of day 100 grade 2 to 4 and 3 to 4 acute GVHD was 52% and 6%, respectively. Chronic GVHD at 2 years was 35%. For patients treated with 2000 cGy, with a median follow-up duration of 12.3 months, 1-year relapse/progression, progression-free survival, and overall survival rates were 17%, 74%, and 83%, respectively. In conclusion, HaploHCT-TMLI with PTCy was safe and feasible in our high-risk patient population with promising outcomes.
| S-EPMC9327543 | biostudies-literature
Project description:The purpose of this study was to develop dosimetry verification procedures for volumetric-modulated arc therapy (VMAT)-based total marrow irradiation (TMI). The VMAT based TMI plans were generated for three patients: one child and two adults. The planning target volume (PTV) was defined as bony skeleton, from head to mid-femur, with a 3 mm margin. The plan strategy similar to published studies was adopted. The PTV was divided into head and neck, chest, and pelvic regions, with separate plans each of which is composed of 2-3 arcs/fields. Multiple isocenters were evenly distributed along the patient's axial direction. The focus of this study is to establish a dosimetry quality assurance procedure involving both two-dimensional (2D) and three-dimensional (3D) volumetric verifications, which is desirable for a large PTV treated with multiple isocenters. The 2D dose verification was performed with film for gamma evaluation and absolute point dose was measured with ion chamber, with attention to the junction between neighboring plans regarding hot/cold spots. The 3D volumetric dose verification used commercial dose reconstruction software to reconstruct dose from electronic portal imaging devices (EPID) images. The gamma evaluation criteria in both 2D and 3D verification were 5% absolute point dose difference and 3 mm of distance to agreement. With film dosimetry, the overall average gamma passing rate was 98.2% and absolute dose difference was 3.9% in junction areas among the test patients; with volumetric portal dosimetry, the corresponding numbers were 90.7% and 2.4%. A dosimetry verification procedure involving both 2D and 3D was developed for VMAT-based TMI. The initial results are encouraging and warrant further investigation in clinical trials.
| S-EPMC5714362 | biostudies-literature
Project description:Sickle cell disease (SCD) is a serious global health problem, and currently, the only curative option is hematopoietic stem cell transplant (HCT). However, myeloablative total body irradiation (TBI)-based HCT is associated with high mortality/morbidity in SCD patients. Therefore, reduced-intensity (2-4 Gy) total body radiation (TBI) is currently used as a conditioning regimen resulting in mixed chimerism with the rescue of the SCD disease characteristic features. However, donor chimerism gradually reduces in a few years, resulting in a relapse of the SCD features, and organ toxicities remained the primary concern for long-term survivors. Targeted marrow irradiation (TMI) is a novel technique developed to deliver radiation to the desired target while sparing vital organs and is successfully used for HCT in refractory/relapsed patients with leukemia. However, it is unknown if TMI will be an effective treatment for a hematological disorder like SCD without adverse effects seen on TBI. Therefore, we examined preclinical feasibility to determine the tolerated dose escalation, its impact on donor engraftment, and reduction in organ damage using our recently developed TMI in the humanized homozygous Berkley SCD mouse model (SS). We show that dose-escalated TMI (8:2) (8 Gy to the bone marrow and 2 Gy to the rest of the body) is tolerated with reduced organ pathology compared with TBI (4:4)-treated mice. Furthermore, with increased SCD control (AA) mice (25 million) donor BM cells, TMI (8:2)-treated mice show successful long-term engraftment while engraftment failed in TBI (2:2)-treated mice. We further evaluated the benefit of dose-escalated TMI and donor cell engraftment in alleviating SCD features. The donor engraftment in SCD mice completely rescues SCD disease features including recovery in RBCs, hematocrit, platelets, and reduced reticulocytes. Moreover, two-photon microscopy imaging of skull BM of transplanted SCD mice shows reduced vessel density and leakiness compared to untreated control SCD mice, indicating vascular recovery post-BMT.
| S-EPMC9485604 | biostudies-literature