Treatment planning of total marrow irradiation with intensity-modulated spot-scanning proton therapy

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

Feasibility of a Novel Sparse Orthogonal Collimator–Based Preclinical Total Marrow Irradiation for Enhanced Dosimetric Conformality

Total marrow irradiation (TMI) has significantly improved radiation conditioning for hematopoietic cell transplantation in hematologic diseases by reducing conditioning-induced toxicities and improving survival outcomes in relapsed/refractory patients. Recently, preclinical three-dimensional image–guided TMI has been developed to enhance mechanistic understanding of the role of TMI and to support the development of experimental therapeutics. However, a dosimetric comparison between preclinical and clinical TMI reveals that the preclinical TMI treatment lacks the ability to reduce the dose to some of the vital organs that are very close to the skeletal system and thus limits the ability to evaluate radiobiological relevance. To overcome this limit, we introduce a novel Sparse Orthogonal Collimator (SOC)–based TMI and evaluate its ability to enhance dosimetric conformality. The SOC-TMI–based dose modulation technique significantly improves TMI treatment planning by reducing radiation exposures to critical organs that are close to the skeletal system that leads to reducing the gap between clinical and preclinical TMI

Prototype Small-Animal PET-CT Imaging System for Image-Guided Radiation Therapy

Molecular imaging is becoming essential for precision targeted radiation therapy, yet progress is hindered from a lack of integrated imaging and treatment systems. We report the development of a prototype positron emission tomography (PET) scanner integrated into a commercial cone beam computed tomography (CBCT) based small animal irradiation system for molecular-image-guided, targeted external beam radiation therapy. The PET component consists of two rotating Hamamatsu time-of-flight PET modules positioned with a bore diameter of 101.6 mm and a radial field-of-view of 53.1 mm. The measured energy resolution after linearity correction at 511 KeV was 12.9% and the timing resolution was 283.6 ps. The measured spatial resolutions at the field-of-view center and 5 mm off the radial center were 2.6 mm × 2.6 mm × 1.6 mm and 2.6 mm × 2.6 mm × 2.7 mm respectively. 18F-Fluorodeoxyglucose-based PET imaging of a NEMA NU 4-2008 phantom resolved cylindrical volumes with diameters as small as 3 mm. To validate the system in-vivo, we performed 64Cu-DOTA-M5A PET and computed tomography (CT) imaging of carcinoembryonic antigen (CEA)-positive colorectal cancer in athymic nude mice and compared the results with a commercially available Siemens Inveon PET/CT system. The prototype PET system performed comparably to the Siemens system for identifying the location, size, and shape of tumors. Regions of heterogeneous 64Cu-DOTA-M5A uptake were observed. Using 64Cu-DOTA-M5A PET and CT images, a Monte Carlo-based radiation treatment plan was created to escalate the dose to the 64Cu-DOTA-M5A-based, highly active, biological target volume while largely sparing the normal tissue. Results demonstrate the feasibility of molecular-image-guided treatment plans using the prototype theranostic system