Impact of the Dose and Fractionation in the Interstitial Brachytherapy to the Treatment Outcome for Patients with Localized Prostate Carcinoma

Brahiterapija visokim brzinama doze (HDR–BT) predstavlja efikasan modalitet zračenja kod pacijenata sa lokalizovanim karcinomom prostate (CaP) svih rizika. Za razliku od transkutane radioterapije i brahiterapije niskim brzinama doze (LDR–BT), kod ove grupe pacijenata u intersticijalnoj HDR–BT još uvek nisu jednoznačno definisane ukupne doze zračenja, način frakcionisanja kod pacijenata sa lokalizovanim CaP različitih rizika. U periodu od 2009–2018.god. HDR–BT kao jedinim načinom lečenja (monoterapija) u Opštoj bolnici Medicinski sistem Beograd, lečeno je 35 pacijenata (6 (17,1%) pacijenata niskog rizika, 21 (60%) pacijent srednjeg rizika i 8 (22,9%) pacijenata visokog rizika) sa lokalizovanim CaP različitih rizika od relapsa i progresije bolesti. Grupe pacijenata sa srednjim i visokim rizikom spojene su u jednu grupu (grupa sa višim rizikom). Tehnika sprovođenja HDR–BT, osim u pojedinačnim specifičnim detaljima, bila je slična kao i kod LDR–BT. Aplikacija igala, segmentacija, delineacija i planiranje HDR–BT vršeno je korišćešem transrektalnog ultrazvuka (TRUS) i izocetričnog radioskopskog C–luka, a zračenje je sprovedeno na uređaju Microselectron HDR sa zatvorenim radioaktivnim izvorom 192Ir početne aktivnosti 370 GBq. Aplikovane terapijske doze (TD), u opsegu od 30–57 Gy frakcionisane su u 3–4 nezavisne frakcije sa razmakom od 2–3 nedelje između frakcija, a individualizovane su prema nivou rizika, stanju organa u riziku (OAR) i kvalitetu aplikacije (indeksu prekrivanja CTV sa planiranom terapijskom dozom (CI100%) i mogućnošću zaštite OAR). Uspešnost terapije ocenjivana je postignutom biohemijskom kontrolom (BFS – biochemical–free–survival), prema ASTRO i Phoenix kriterijumima, kao i ukupnim preživljavanjem u periodu od 5 godina (2–9 godina) posle sprovedene terapije. U niskorizičnoj grupi pacijenata lečenih HDR–BT, BFS je postignuta kod svih pacijenata kao i ukupno preživljavanje. U grupi pacijenata sa višim rizikom BFS je postignuta kod 95,8% lečenih pacijenata, a ukupno 5–to godišnje preživljavanje je 96,4%. BFS u ovom istraživanju se pokazala statistički značajnije bolja nego ona koju su prikazali drugi autori. Na osnovu rizika, nivoa PSA, TD i indeksa pokrivenosti CTV sa TD, izvršeno je modelovanje terapijskih parametara korišćenjem MANN (multilauyer artificial neural network). Određena optimalna doza zračenja (TD) u HDR–BT lokalizovanog CaP niskog rizika je 40,7 Gy za CI100% = 1,01. Kod viših rizika TD = 50,9 Gy za CI100% = 1,6. TD se frakcioniše u 4 nezavisne frakcije sa razmakom od 2–3 nedelje. Ovakav izbor parametara HDR–BT (TD, CI100%, i način frakcionisanja), uz individualizaciju i kontrolu u toku svake aplikacije, obezbedio bi prihvatljiv nivo kasnih postiradijacionih komplikacija gradusa G1–G3 na uretri (< 17% ukupnog broja lečenih pacijenata), uz minimimalne komplikacije na rektumu (pretežno G1–G2) i zanemarljive komplikacije na mokraćnoj bešici.High–dose rate brachytherapy (HDR–BT) is an effective therapy modality for patients with localized prostate cancer (CaP) of all risks. In contrast to an external beam radiotherapy and low–dose rate brachytherapy (LDR–BT), in these patients, the interstitial HDR–BT, the total radiation dose and fractionation is not unambiguously defined. Between 2009–2018 35 patients with localized CaP (6 (17.1%) low–risk patients, 21 (60%) patients medium–risk and 8 (22.9%) high–risk) were treated with HDR–BT, as the only treatment (monotherapy) in the General Hospital Medical System Belgrade. The group of patients with medium–risk and high–risk were merged into a single group (group with a higher–risk). Technique implementation of HDR–BT was similar as in the LDR–BT. Application of needles, segmentation, delineation, and planning of HDR–BT was performed with transrectal ultrasound (TRUS) and izocentrically mounted radioscopic C–arm. Irradiation was done on the Microselectron–HDR brachytherapy unit with a sealed radioactive source 192Ir (370 GBq). The dose (TD), in the range of 30–57 Gy was given fractionated in independent fractions (3–4) with a pause of 2–3 weeks between fractions. TD was individualized according to the risk, the conditions of organs at risk (OAR) and quality of the application (coverage index CI100%), as well as, the ability to protect OAR. Treatment result was evaluated by the achieved biochemical control (BFS – biochemical–free–survival) according to ASTRO and/or Phoenix criteria, as well as an overall survival in the period of 5 years (2–9 years) after the completion of the treatment. In the low–risk group, BFS has been achieved in all patients and overall survival rate is 100%. In the group of patients with higher risk BFS was achieved in 95.8% of treated patients, and 5–year survival rate was 96.4%. BFS in this study was proved to be statistically significantly better than showed by other authors. On the basis of the risk, the level of PSA, TD and CI100%, modeling was performed using the MANN (multilayer artificial neural network). The determined optimal dose TD for localized CaP of low risk is 40.7 Gy for CI100% = 1.0. At higher risk TD = 50.9 Gy for CI100% = 1.6. TD was given in 4 independent fractions with the interval of 2–3 weeks between each fraction. These HDR–BT parameters (TD, CI100%, and the fractionation scheme) with the individualization and control during each application would provide an acceptable level of late complications grade G1–G3 to the urethra (in less than 17% of treated patients), with minimum complications on the rectum (predominantly grade G1–G2) and insignificant complications rate on the urinary bladder

Prostate Volume Segmentation in TRUS using Hybrid Edge-Bhattacharyya Active Surfaces

International audience—Objective: We present a new hybrid edge and region-based parametric deformable model, or active surface, for prostate volume segmentation in transrectal ultrasound (TRUS) images. Methods: Our contribution is threefold. First, we develop a new edge detector derived from the radial bas-relief approach, allowing for better scalar prostate edge detection in low contrast configurations. Second, we combine an edge-based force derived from the proposed edge detector with a new region-based force driven by the Bhattacharyya gradient flow and adapted to the case of parametric active surfaces. Finally, we develop a quasi-automatic initialization technique for deformable models by analyzing the profiles of the proposed edge detector response radially to obtain initial landmark points towards which an initial surface model is warped. Results: We validate our method on a set of 36 TRUS images for which manual delineations were performed by two expert radiation oncologists, using a wide variety of quantitative metrics. The proposed hybrid model achieved state-of-the art segmentation accuracy. Conclusion: Results demonstrate the interest of the proposed hybrid framework for accurate prostate volume segmentation. Significance: This paper presents a modular framework for accurate prostate volume segmentation in TRUS, broadening the range of available strategies to tackle this open problem

Brain and Human Body Modeling

This open access book describes modern applications of computational human modeling with specific emphasis in the areas of neurology and neuroelectromagnetics, depression and cancer treatments, radio-frequency studies and wireless communications. Special consideration is also given to the use of human modeling to the computational assessment of relevant regulatory and safety requirements. Readers working on applications that may expose human subjects to electromagnetic radiation will benefit from this book’s coverage of the latest developments in computational modelling and human phantom development to assess a given technology’s safety and efficacy in a timely manner. Describes construction and application of computational human models including anatomically detailed and subject specific models; Explains new practices in computational human modeling for neuroelectromagnetics, electromagnetic safety, and exposure evaluations; Includes a survey of modern applications for which computational human models are critical; Describes cellular-level interactions between the human body and electromagnetic fields

[¹⁸F]fluorination of biorelevant arylboronic acid pinacol ester scaffolds synthesized by convergence techniques

Aim: The development of small molecules through convergent multicomponent reactions (MCR) has been boosted during the last decade due to the ability to synthesize, virtually without any side-products, numerous small drug-like molecules with several degrees of structural diversity.(1) The association of positron emission tomography (PET) labeling techniques in line with the “one-pot” development of biologically active compounds has the potential to become relevant not only for the evaluation and characterization of those MCR products through molecular imaging, but also to increase the library of radiotracers available. Therefore, since the [18F]fluorination of arylboronic acid pinacol ester derivatives tolerates electron-poor and electro-rich arenes and various functional groups,(2) the main goal of this research work was to achieve the 18F-radiolabeling of several different molecules synthesized through MCR. Materials and Methods: [18F]Fluorination of boronic acid pinacol esters was first extensively optimized using a benzaldehyde derivative in relation to the ideal amount of Cu(II) catalyst and precursor to be used, as well as the reaction solvent. Radiochemical conversion (RCC) yields were assessed by TLC-SG. The optimized radiolabeling conditions were subsequently applied to several structurally different MCR scaffolds comprising biologically relevant pharmacophores (e.g. β-lactam, morpholine, tetrazole, oxazole) that were synthesized to specifically contain a boronic acid pinacol ester group. Results: Radiolabeling with fluorine-18 was achieved with volumes (800 μl) and activities (≤ 2 GBq) compatible with most radiochemistry techniques and modules. In summary, an increase in the quantities of precursor or Cu(II) catalyst lead to higher conversion yields. An optimal amount of precursor (0.06 mmol) and Cu(OTf)2(py)4 (0.04 mmol) was defined for further reactions, with DMA being a preferential solvent over DMF. RCC yields from 15% to 76%, depending on the scaffold, were reproducibly achieved. Interestingly, it was noticed that the structure of the scaffolds, beyond the arylboronic acid, exerts some influence in the final RCC, with electron-withdrawing groups in the para position apparently enhancing the radiolabeling yield. Conclusion: The developed method with high RCC and reproducibility has the potential to be applied in line with MCR and also has a possibility to be incorporated in a later stage of this convergent “one-pot” synthesis strategy. Further studies are currently ongoing to apply this radiolabeling concept to fluorine-containing approved drugs whose boronic acid pinacol ester precursors can be synthesized through MCR (e.g. atorvastatin)