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Radio-ligand therapy (RLT) with177Lu-PSMA-617 is a promising option for patients with metastatic castration-resistant prostate-cancer (mCRPC). A prospective phase-II study (EUDRACT/RSO,2016-002732-32) on mCRPC is ongoing at IRST (Meldola, Italy). A total of 9 patients (median age: 68 y, range: 53–85) were enrolled for dosimetry evaluation of parotid glands (PGs), kidneys, red marrow (RM) and whole body (WB). Folic polyglutamate tablets were orally administered as PGs protectors and 500 mL of a 10% mannitol solution was intravenously infused to reduce kidney uptake. The whole body planar image (WBI) and blood samples were acquired at different times post infusion (1 h, 16–24 h, 36–48 h and 120 h). Dose calculation was performed with MIRD formalism (OLINDA/EXM software). The median effective half-life was 33.0 h (range: 25.6–60.7) for PGs, 31.4 h (12.2–80.6) for kidneys, 8.2 h (2.5–14.7) for RM and 40.1 h (31.6–79.7) for WB. The median doses were 0.48 mGy/MBq (range: 0.33–2.63) for PGs, 0.70 mGy/MBq (0.26–1.07) for kidneys, 0.044 mGy/MBq (0.023–0.067) for RM and 0.04 mGy/MBq (0.02–0.11) for WB. A comparison with previously published dosimetric data was performed and a significant difference was found for PGs while no significant difference was observed for the kidneys. For PGs, the possibility of reducing uptake by administering glutamate tablets during RLT seems feasible while further research is warranted for a more focused evaluation of the reduction in kidney uptake.

Purpose:To validate and compare the deformable image registration and parotid contour propagation process for head and neck magnetic resonance imaging in patients treated with radiotherapy using 3 different approaches—the commercial MIM, the open-source Elastix software, and an optimized version of it.Materials and Methods:Twelve patients with head and neck cancer previously treated with radiotherapy were considered. Deformable image registration and parotid contour propagation were evaluated by considering the magnetic resonance images acquired before and after the end of the treatment. Deformable image registration, based on free-form deformation method, and contour propagation available on MIM were compared to Elastix. Two different contour propagation approaches were implemented for Elastix software, a conventional one (DIR_Trx) and an optimized homemade version, based on mesh deformation (DIR_Mesh). The accuracy of these 3 approaches was estimated by comparing propagated to manual contours in terms of average symmetric distance, maximum symmetric distance, Dice similarity coefficient, sensitivity, and inclusiveness.Results:A good agreement was generally found between the manual contours and the propagated ones, without differences among the 3 methods; in few critical cases with complex deformations, DIR_Mesh proved to be more accurate, having the lowest values of average symmetric distance and maximum symmetric distance and the highest value of Dice similarity coefficient, although nonsignificant. The average propagation errors with respect to the reference contours are lower than the voxel diagonal (2 mm), and Dice similarity coefficient is around 0.8 for all 3 methods.Conclusion:The 3 free-form deformation approaches were not significantly different in terms of deformable image registration accuracy and can be safely adopted for the registration and parotid contour propagation during radiotherapy on magnetic resonance imaging. More optimized approaches (as DIR_Mesh) could be preferable for critical deformations.

Early density and volume variations accurately predict final changes of parotid glands. A higher longitudinally assessed score of acute xerostomia is well predicted by higher rΔρ and rΔvol in the first two weeks of treatment: best cut-off values were -0.50 HU/day and -380 mm(3)/day for rΔρ and rΔvol respectively. Further studies are necessary to definitively assess the potential of early density/volume changes in identifying more sensitive patients at higher risk of experiencing xerostomia.

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Neuroblastoma (NB) is a pediatric tumor presenting at diagnosis either as localized or metastatic disease, which mainly involves the bone marrow (BM). The physical occupancy of BM space by metastatic NB cells has been held responsible for impairment of BM function. Here, we investigated whether localized or metastatic NB may alter hematopoietic lineages’ maturation and release of mature cells in the periphery, through gene expression profiling, analysis of BM smears, cell blood count and flow cytometry analysis.Gene ontology and disease-associated analysis of the genes significantly under-expressed in BM resident cells from children with localized and metastatic NB, as compared to healthy children, indicated anemia, blood group antigens, and heme and porphyrin biosynthesis as major functional annotation clusters. Accordingly, in children with NB there was a selective impairment of erythrocyte maturation at the ortho-chromic stage that resulted in reduced erythrocyte count in the periphery, regardless of the presence of metastatic cells in the BM. By considering all NB patients, low erythrocyte count at diagnosis associated with worse survival. Moreover, in the subset of metastatic patients, low erythrocyte count, hemoglobin and hematocrit and high red cell distribution width at follow-up also associated with worse outcome.These observations provide an alternative model to the tenet that infiltrating cells inhibit BM functions due to physical occupancy of space and may open a new area of research in NB to understand the mechanism(s) responsible for such selective impairment.