Evaluation of Functional Marrow Irradiation Based on Skeletal Marrow Composition Obtained Using Dual-Energy Computed Tomography

Magome, Taiki; Takahashi, Yutaka; Arentsen, Luke; Holtan, Shernan G.; Verneris, Michael R.; Brown, J.K.; Haga, Akihiro; Nakagawa, Keiichi; Chakrabarty, Jennifer L. Holter; Giebel, Sebastian; Wong, Jeffrey Y.C.; Dusenbery, Kathryn E.; Storme, Guy; Song, Hui

doi:10.1016/j.ijrobp.2016.06.2459

Cited by 15 publications

(17 citation statements)

References 30 publications

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“…Particularly in the vertebrae and pelvic bones, again containing most of the total bone marrow, the dose distributions were visually observed to have acceptable coverage for both the TMI and TBI plans, providing confidence of reasonable dosimetric parity to the marrow between the two modalities. However, it would be impractical or impossible to obtain accurate marrow doses between TMI and TBI without patient‐specific maps of the distribution of active marrow, for example, via SPECT/CT or dual‐energy CT marrow imaging …”

Section: Discussionmentioning

confidence: 99%

Organ sparing of linac‐based targeted marrow irradiation over total body irradiation

Warrell

Colussi

Swanson

et al. 2019

J Applied Clin Med Phys

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Purpose: Targeted 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.Methods: TMI 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.Results: For 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.Conclusion: TMI 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. K E Y W O R D S equivalent uniform dose, gEUD, TBI, targeted marrow irradiation, TMI, total body irradiation ---

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Section: Discussionmentioning

confidence: 99%

Organ sparing of linac‐based targeted marrow irradiation over total body irradiation

Warrell

Colussi

Swanson

et al. 2019

J Applied Clin Med Phys

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“…The RM and YM were segmented from DECT based on a basis material decomposition by using QCT Pro (Mindways Software, Austin, Texas), with details reported previously. 10 , 12 The volumetric overlap between FLT-avid and marrow regions was evaluated by Dice similarity coefficient (DSC). 13 Binary PET images were created for the calculation of DSCs by changing the SUV threshold value.…”

Section: Methodsmentioning

confidence: 99%

Whole-Body Distribution of Leukemia and Functional Total Marrow Irradiation Based on FLT-PET and Dual-Energy CT

et al. 2017

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This report describes a multimodal whole-body 3′-deoxy-3′[(18)F]-fluorothymidine positron emission tomography (FLT-PET) and dual-energy computed tomography (DECT) method to identify leukemia distribution within the bone marrow environment (BME) and to develop disease- and/or BME-specific radiation strategies. A control participant and a newly diagnosed patient with acute myeloid leukemia prior to induction chemotherapy were scanned with FLT-PET and DECT. The red marrow (RM) and yellow marrow (YM) of the BME were segmented from DECT using a basis material decomposition method. Functional total marrow irradiation (fTMI) treatment planning simulations were performed combining FLT-PET and DECT imaging to differentially target irradiation to the leukemia niche and the rest of the skeleton. Leukemia colonized both RM and YM regions, adheres to the cortical bone in the spine, and has enhanced activity in the proximal/distal femur, suggesting a potential association of leukemia with the BME. The planning target volume was reduced significantly in fTMI compared with conventional TMI. The dose to active disease (standardized uptake value >4) was increased by 2-fold, while maintaining doses to critical organs similar to those in conventional TMI. In conclusion, a hybrid system of functional–anatomical–physiological imaging can identify the spatial distribution of leukemia and will be useful to both help understand the leukemia niche and develop targeted radiation strategies.

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“…Consequently, whereas conventional single-energy quantitative computed tomography methods underestimate volumetric BMD measurements, DECT can correct for BMAT, resulting in more accurate densitometric measurements (118)(119)(120). Furthermore, BMAT content can be explored reliably, as good correlations have been reported with WFI and histology on cadavers (121,122), and 1H-MRS in vivo (123). Potential interesting applications exist in oncology, to follow marrow fat expansion and BMD involution in patients after chemotherapy or radiotherapy (124).…”

Section: Alternatives To 1 H-mrs and Wfimentioning

confidence: 99%

Reporting Guidelines, Review of Methodological Standards, and Challenges Toward Harmonization in Bone Marrow Adiposity Research. Report of the Methodologies Working Group of the International Bone Marrow Adiposity Society

et al. 2020

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The interest in bone marrow adiposity (BMA) has increased over the last decade due to its association with, and potential role, in a range of diseases (osteoporosis, diabetes, anorexia, cancer) as well as treatments (corticosteroid, radiation, chemotherapy, thiazolidinediones). However, to advance the field of BMA research, standardization of methods is desirable to increase comparability of study outcomes and foster collaboration. Therefore, at the 2017 annual BMA meeting, the International Bone Marrow Adiposity Society (BMAS) founded a working group to evaluate methodologies in BMA research. All BMAS members could volunteer to participate. The working group members, who are all active preclinical or clinical BMA researchers, searched the literature for articles investigating BMA and discussed the results during personal and telephone conferences. According to the consensus opinion, both based on the review of the literature and on expert opinion, we describe existing methodologies and discuss the challenges and future directions for (1) histomorphometry of bone marrow adipocytes, (2) ex vivo BMA imaging, (3) in vivo BMA imaging, (4) cell isolation, culture, differentiation and in vitro modulation of primary bone marrow adipocytes and bone marrow stromal cell precursors, (5) lineage tracing and in vivo BMA modulation, and (6) BMA biobanking. We identify as accepted standards in BMA research: manual histomorphometry and osmium tetroxide 3D contrast-enhanced µCT for ex vivo quantification, specific MRI sequences (WFI and H-MRS) for in vivo studies, and RT-qPCR with a minimal four gene panel or lipid-based assays for in vitro quantification of bone marrow adipogenesis. Emerging techniques are described which may soon come to complement or substitute these gold standards. Known confounding factors and minimal reporting standards are presented, and their use is encouraged to facilitate comparison across studies. In conclusion, specific BMA methodologies have been developed. However, important challenges remain. In particular, we advocate for the harmonization of methodologies, the precise reporting of known confounding factors, and the identification of methods to modulate BMA independently from other tissues. Wider use of existing animal models with impaired BMA production (e.g., Pfrt −/− , Kit W/W−v) and development of specific BMA deletion models would be highly desirable for this purpose.

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Evaluation of Functional Marrow Irradiation Based on Skeletal Marrow Composition Obtained Using Dual-Energy Computed Tomography

Cited by 15 publications

References 30 publications

Organ sparing of linac‐based targeted marrow irradiation over total body irradiation

Organ sparing of linac‐based targeted marrow irradiation over total body irradiation

Whole-Body Distribution of Leukemia and Functional Total Marrow Irradiation Based on FLT-PET and Dual-Energy CT

Reporting Guidelines, Review of Methodological Standards, and Challenges Toward Harmonization in Bone Marrow Adiposity Research. Report of the Methodologies Working Group of the International Bone Marrow Adiposity Society

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