Bilbao-Jaureguízar, J. (José Ignacio)

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    In Vitro Model for Simulating Drug Delivery during Balloon-Occluded Transarterial Chemoembolization.
    (MDPI, 2021) Aramburu-Montenegro, J. (Jorge); Antón-Remírez, R. (Raúl); Fukamizu, J. (Junichi); Nozawa, D. (Daiki); Ramos-González, J. (Juan Carlos); Sangro, B. (Bruno); Bilbao-Jaureguízar, J. (José Ignacio); Tomita, K. (Kosuke); Matsumoto, T. (Tomohiro); Hasebe, T. (Teremitsu)
    Simple Summary Liver cancer is one of the leading causes of cancer-related deaths worldwide and balloon-occluded transarterial chemoembolization (B-TACE) has emerged as a safe and effective treatment for liver cancer. However, the hemodynamic alterations that are responsible for the successfulness of the treatment and are produced by the microballoon catheter used during the treatment are not yet well understood. In this study, we developed an in vitro model (IVM) that can simulate B-TACE. We designed clinically relevant experiments, and we obtained clinically realistic results. We conclude that the IVM allows for a visual understanding of a complex phenomenon (i.e., the blood flow redistribution after balloon occlusion) and it could be used as a base for future sophisticated and even patient-specific IVMs; in addition, it could be used to conduct IVM-based research on B-TACE. Background: Balloon-occluded transarterial chemoembolization (B-TACE) has emerged as a safe and effective procedure for patients with liver cancer, which is one of the deadliest types of cancer worldwide. B-TACE consist of the transcatheter intraarterial infusion of chemotherapeutic agents, followed by embolizing particles, and it is performed with a microballoon catheter that temporarily occludes a hepatic artery. B-TACE relies on the blood flow redistribution promoted by the balloon-occlusion. However, flow redistribution phenomenon is not yet well understood. Methods: This study aims to present a simple in vitro model (IVM) where B-TACE can be simulated. Results: By visually analyzing the results of various clinically-realistic experiments, the IVM allows for the understanding of balloon-occlusion-related hemodynamic changes and the importance of the occlusion site. Conclusion: The IVM can be used as an educational tool to help clinicians better understand B-TACE treatments. This IVM could also serve as a base for a more sophisticated IVM to be used as a research tool.
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    3D voxel-based dosimetry to predict contralateral hypertrophy and an adequate future liver remnant after lobar radioembolization
    (Springer, 2021) Grisanti-Vollbracht, F. (Fabiana); Prieto, E. (Elena); Bastidas, J.F. (Juan Fernando); Sancho-Rodriguez, L. (Lidia); Rodrigo, P. (Pablo); Beorlegui, C. (Carmen); Iñarrairaegui, M. (Mercedes); Bilbao-Jaureguízar, J. (José Ignacio); Sangro, B. (Bruno); Rodriguez-Fraile, M. (Macarena)
    Introduction: Volume changes induced by selective internal radiation therapy (SIRT) may increase the possibility of tumor resection in patients with insufficient future liver remnant (FLR). The aim was to identify dosimetric and clinical parameters associated with contralateral hepatic hypertrophy after lobar/extended lobar SIRT with 90Y-resin microspheres. Materials and methods: Patients underwent 90Y PET/CT after lobar or extended lobar (right + segment IV) SIRT. 90Y voxel dosimetry was retrospectively performed (PLANET Dose; DOSIsoft SA). Mean absorbed doses to tumoral/non-tumoral-treated volumes (NTL) and dose-volume histograms were extracted. Clinical variables were collected. Patients were stratified by FLR at baseline (T0-FLR): < 30% (would require hypertrophy) and ≥ 30%. Changes in volume of the treated, non-treated liver, and FLR were calculated at < 2 (T1), 2–5 (T2), and 6–12 months (T3) post-SIRT. Univariable and multivariable regression analyses were performed to identify predictors of atrophy, hypertrophy, and increase in FLR. The best cut-off value to predict an increase of FLR to ≥ 40% was defined using ROC analysis. Results: Fifty-six patients were studied; most had primary liver tumors (71.4%), 40.4% had cirrhosis, and 39.3% had been previously treated with chemotherapy. FLR in patients with T0-FLR < 30% increased progressively (T0: 25.2%; T1: 32.7%; T2: 38.1%; T3: 44.7%). No dosimetric parameter predicted atrophy. Both NTL-Dmean and NTL-V30 (fraction of NTL exposed to ≥ 30 Gy) were predictive of increase in FLR in patients with T0 FLR < 30%, the latter also in the total cohort of patients. Hypertrophy was not significantly associated with tumor dose or tumor size. When ≥ 49% of NTL received ≥ 30 Gy, FLR increased to ≥ 40% (accuracy: 76.4% in all patients and 80.95% in T0-FLR < 30% patients). Conclusion: NTL-Dmean and NTL exposed to ≥ 30 Gy (NTL-V30) were most significantly associated with increase in FLR (particularly among patients with T0-FLR < 30%). When half of NTL received ≥ 30 Gy, FLR increased to ≥ 40%, with higher accuracy among patients with T0-FLR < 30%.
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    A proof-of-concept study of the in-vivo validation of a computational fluid dynamics model of personalized radioembolization
    (2021) Antón, R. (Raúl); Antoñana, J. (Javier); Aramburu-Montenegro, J. (Jorge); Ezponda, A. (Ana); Prieto, E. (Elena); Andonegui-Isasa, A. (Asier); Ortega, J. (Julio); Vivas, I. (Isabel); Sancho-Rodriguez, L. (Lidia); Sangro, B. (Bruno); Bilbao-Jaureguízar, J. (José Ignacio); Rodriguez-Fraile, M. (Macarena)
    Radioembolization (RE) with yttrium-90 (90Y) microspheres, a transcatheter intraarterial therapy for patients with liver cancer, can be modeled computationally. The purpose of this work was to correlate the results obtained with this methodology using in vivo data, so that this computational tool could be used for the optimization of the RE procedure. The hepatic artery three-dimensional (3D) hemodynamics and microsphere distribution during RE were modeled for six 90Y-loaded microsphere infusions in three patients with hepatocellular carcinoma using a commercially available computational fluid dynamics (CFD) software package. The model was built based on in vivo data acquired during the pretreatment stage. The results of the simulations were compared with the in vivo distribution assessed by 90Y PET/CT. Specifically, the microsphere distribution predicted was compared with the actual 90Y activity per liver segment with a commercially available 3D-voxel dosimetry software (PLANET Dose, DOSIsoft). The average difference between the CFD-based and the PET/CT-based activity distribution was 2.36 percentage points for Patient 1, 3.51 percentage points for Patient 2 and 2.02 percentage points for Patient 3. These results suggest that CFD simulations may help to predict 90Y-microsphere distribution after RE and could be used to optimize the RE procedure on a patient-specific basis.