Search Results (13)

Background/Objectives: Microwave ablation (MWA) is the leading therapy method for treating patients with liver cancer. MWA simulation is used to further improve the therapy and to help develop new devices. Methods: A water-cooled ablation needle was reconstructed. MWA simulations of a polyacrylamide phantom were carried out and compared with a representative clinical example (tumor diameter: 8.75 mm). The Arrhenius damage model and a critical temperature approach of 60 °C were applied to assess the necrosis zones. Finally, the simulation results were compared to the corresponding MR measurements. Results: Most of the heating in the simulation took place at a distance of 5 mm along the transverse axis and 20 mm along the longitudinal axis above the needle tip. The calculated Dice scores for the Arrhenius model were 0.77/0.53 for the phantom/clinical case. For the critical temperature approach, Dice scores of 0.60/0.66 for the phantom/clinical case were achieved. Conclusions: The comparison between simulated and measured temperature increases showed an excellent agreement. However, differences in the predicted necrosis volume might be caused by omitting consideration of the heat sink effect, especially in the clinical case. Nevertheless, this workflow enables short MWA simulation times (approximately 3 min) and demonstrates a step towards possible integration into daily clinical use. Full article

Nanobiomaterials (NBMs) have tremendous potential applications including in cancer diagnosis and treatment. However, the health and environmental effects of NBMs must be thoroughly assessed to ensure safety. Fe₃O₄ (magnetite) nanoparticles coated with polyethylene glycol (PEG) and poly (lactic-co-glycolic acid) (PLGA) were one of the focus NBMs within the EU project BIORIMA. Fe₃O₄ PEG-PLGA has been proposed to be used as a contrast agent in magnetic resonance imaging for the identification of solid tumors and has revealed low cytotoxicity in several cell lines. However, the effects of Fe₃O₄ PEG-PLGA have not been assessed in terrestrial environments, the eventual final sink of most materials. In the present study, the effects of Fe₃O₄ PEG-PLGA and its precursor, (un-coated) Fe₃O₄ NMs, were assessed in soil model invertebrates Enchytraeus crypticus (Oligochaeta) and Folsomia candida (Collembola). The endpoints were survival, reproduction, and size, based on the standard OECD test (28 days) and its extension (56 days). The results showed no toxicity for any of the endpoints evaluated, indicating that the NBM Fe₃O₄ PEG-PLGA poses no unacceptable risk to the terrestrial environment. Full article

Liver cancer remains a leading cause of cancer-related deaths worldwide despite numerous advances in treatment. While surgical resection remains the gold standard for curative treatment, it is only possible for a minority of patients. Thermal ablation is an effective option for the treatment of smaller tumors; however, its use is limited to tumors that are not located in proximity to sensitive structures due to the heat sink effect and the potential of thermal damage. Irreversible electroporation (IRE) is a non-thermal ablative modality that can deliver targeted treatment and the effective destruction of tumors that are in close proximity to or even surrounding vascular or biliary ducts with minimal damage to these structures. IRE produces short pulses of high-frequency energy which opens pores in the lipid bilayer of cells leading to apoptosis and cell death. IRE has been utilized clinically for over a decade in the treatment of liver cancers with multiple studies documenting an acceptable safety profile and high efficacy rates. Full article

Most Prostate Specific Membrane Antigens (PSMAs) targeting small molecules accumulate in the salivary glands (SGs), raising concerns about SG toxicity, especially after repeated therapies or therapy with ²²⁵Ac-labeled ligands. SG toxicity is assessed clinically by the severity of patient-reported xerostomia, but this parameter can be challenging to objectively quantify. Therefore, we explored the feasibility of using SG volume as a biomarker for toxicity. In 21 patients with late-stage metastatic resistant prostate cancer (mCRPC), the PSMA volume and ligand uptake of SG were analyzed retrospectively before and after two cycles of ¹⁷⁷Lu-PSMA (LuPSMA; cohort A) and before and after one cycle of ²²⁵Ac-PSMA-617 (AcPSMA, cohort B). Mean Volume-SG in cohort A was 59 ± 13 vs. 54 ± 16 mL (−10%, p = 0.4), and in cohort B, it was 50 ± 13 vs. 40 ± 11 mL (−20%, p = 0.007), respectively. A statistically significant decrease in the activity concentration in the SG was only observed in group B (SUV_mean: 9.2 ± 2.8 vs. 5.3 ± 1.8, p < 0.0001; vs. A: SUV_mean: 11.2 ± 3.3 vs. 11.1 ± 3.5, p = 0.8). SG volume and PSMA-ligand uptake are promising markers to monitor the SG toxicity after a PSMA RLT. Full article

¹⁷⁷Lu-PSMA-617 radioligand therapy (¹⁷⁷Lu-PSMA-RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC) currently consists of 4–6 cycles of 6.0–7.4 GBq of ¹⁷⁷Lu-PSMA-617 each every 6–8 weeks. While safety and efficacy could be demonstrated in larger prospective trials irrespective of the tumor burden at ¹⁷⁷Lu-PSMA RLT initiation, increased renal absorbed doses due to a reduced tumor sink effect in early responding, oligometastatic mCRPC patients pose difficulties. Response-adapted, dose distributing, intermittent treatment with up to six cycles has not been routinely performed, due to concerns about the potential loss of disease control. Treatment was discontinued in 19 early-responding patients with oligometastatic tumor burden after two (IQR 2–3) cycles of ¹⁷⁷Lu-PSMA-RLT and 6.5 ± 0.7 GBq per cycle and resumed upon ⁶⁸Ga-PSMA-11-PET/CT-based progression (according to the PCWG3 criteria). Subsequent treatment breaks were imposed if a PSMA-based imaging response could be achieved. A total of five (IQR 3–6) cycles reaching a cumulative activity of 32 ± 11 GBq were applied. A routine blood work-up including blood counts and liver and renal function was measured throughout the ¹⁷⁷Lu-PSMA-RLT and follow-up to grade toxicity according to CTCAE v5.0 criteria. Survival outcome was calculated based on the Kaplan–Meier method. In total, treatment-free periods of 9 (IQR 6–17) cumulative months and the application of ¹⁷⁷Lu-PSMA-RLT cycles over 16 (IQR 9–22) months could be achieved. Fifteen (84%) patients responded to subsequent cycles after the first treatment break and in 7/19 (37%) patients, intermittent ¹⁷⁷Lu-PSMA-RLT consisted of ≥2 treatment breaks. The median PFS was 27 months (95% CI: 23–31) and overall survival was 45 months (95% CI: 28–62). No grade ≥3 hematological or renal toxicities could be observed during the 45 ± 21 months of follow-up. The cumulative mean renal absorbed dose was 16.7 ± 8.3 Gy and 0.53 ± 0.21 Gy/GBq. Intermittent radioligand therapy with ¹⁷⁷Lu-PSMA-617 is feasible in early-responding patients with oligometastatic disease. A late onset of progression after subsequent cycles and the absence of significant toxicity warrants further investigation of the concept of intermittent treatment in selected patients. Full article

Purpose: Develop a treatment planning framework for neurosurgeons treating high-grade gliomas with LITT to minimize the learning curve and improve tumor thermal dose coverage. Methods: Deidentified patient images were segmented using the image segmentation software Materialize MIMICS©. Segmented images were imported into the commercial finite element analysis (FEA) software COMSOL Multiphysics© to perform bioheat transfer simulations. The laser probe was modeled as a cylindrical object with radius 0.7 mm and length 100 mm, with a constant beam diameter. A modeled laser probe was placed in the tumor in accordance with patient specific patient magnetic resonance temperature imaging (MRTi) data. The laser energy was modeled as a deposited beam heat source in the FEA software. Penne’s bioheat equation was used to model heat transfer in brain tissue. The cerebrospinal fluid (CSF) was modeled as a solid with convectively enhanced conductivity to capture heat sink effects. In this study, thermal damage-dependent blood perfusion was assessed. Pulsed laser heating was modeled based on patient treatment logs. The stationary heat source and pullback heat source techniques were modeled to compare the calculated tissue damage. The developed bioheat transfer model was compared to MRTi data obtained from a laser log during LITT procedures. The application builder module in COMSOL Multiphysics© was utilized to create a Graphical User Interface (GUI) for the treatment planning framework. Results: Simulations predicted increased thermal damage (10–15%) in the tumor for the pullback heat source approach compared with the stationary heat source. The model-predicted temperature profiles followed trends similar to those of the MRTi data. Simulations predicted partial tissue ablation in tumors proximal to the CSF ventricle. Conclusion: A mobile platform-based GUI for bioheat transfer simulation was developed to aid neurosurgeons in conveniently varying the simulation parameters according to a patient-specific treatment plan. The convective effects of the CSF should be modeled with heat sink effects for accurate LITT treatment planning. Full article

This study aims to assess the change in uptake to reference organs, including the liver, parotid and salivary glands after radioligand therapy (RLT) with [¹⁷⁷Lu]Lu-PSMA-617 in relation to pretreatment imaging metrics. Eighty-five patients with mCRPC underwent [⁶⁸Ga]Ga-PSMA-11 PET/CT imaging prior to (pre RLT PET) and after (post RLT PET) a median of 3 (IQR 2-6) RLT cycles with [¹⁷⁷Lu]Lu-PSMA-617. PSMA-positive tumor burden was stratified into 4 groups based on modified PROMISE criteria (oligofocal, multifocal, disseminated, diffuse). Uptake (SUV_mean, SUV_max) in liver tissue, parotid and submandibular glands was measured. A control group was established with 54 patients who had received two separate PET acquisitions following the same protocol (PET1, PET2) within 12 months for localized or oligofocal prostate cancer without RLT in the interim. Baseline uptake values (SUV_mean, SUV_max) in parotid (10.8 ± 3.2, 16.8 ± 5.4) and submandibular glands (11.3 ± 2.8, 18.1 ± 4.7) are 2-fold compared to liver uptake (4.9 ± 1.4, 7.7 ± 2.0), with no significant change between PET 1 and PET 2 in the control group. In the RLT group, increasing tumor burden class is significantly associated with decreasing uptake in the liver (p = 0.013), parotid (p < 0.001) and submandibular glands (p < 0.001); this tumor sink effect by respective tumor burden is widely maintained after RLT (p = 0.011, p < 0.001, p < 0.001). RLT has a significant impact on salivary gland uptake with decreasing values per patient in all groups of disease burden change (up to −30.4% in submandibular glands, p < 0.001), while liver tissue shows rising values in patients with declining tumor burden throughout RLT (+18.6%, p = 0.020). Uptake in liver tissue and salivary glands on [⁶⁸Ga]Ga-PSMA-11 PET/CT imaging is inversely related to tumor burden prior to and following RLT with [¹⁷⁷Lu]Lu-PSMA-617. Per patient, salivary gland uptake is further reduced throughout RLT independently from tumor burden, while changes in liver uptake remain burden-dependent. Liver and salivary gland uptake-derived metrics and segmentation thresholds may thus be of limited value when used as reference for response assessment to RLT. Full article

“Tumor sink effects”, decreased physiological uptake of radiopharmaceuticals due to sequestration by a tumor, may impact radioligand therapy (RLT) toxicity and dosing. We investigated these effects with prostate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals in the healthy organs-at-risk (the parotid glands, kidneys, liver, and spleen) of 33 patients with metastatic castration-resistant prostate cancer (mCRPC). We retrospectively performed three intra-individual comparisons. First, we correlated changes from baseline to post-RLT (after two 177-lutetium (177Lu)-PSMA-617 cycles) in total lesional PSMA (∆TLP) and organ mean standardized uptake values (∆SUVmean). Second, in 25 RLT responders, we compared the organ SUVmean post-RLT versus that at baseline. Lastly, we correlated the baseline TLP and organ SUVmean. Data were acquired via 68-gallium-PSMA-11 positron emission tomography before the first and after the second 177Lu-PSMA-617 cycle. In the parotid glands and spleen, ∆TLP and ∆SUVmean showed a significant inverse correlation (r = −0.40, p = 0.023 and r = −0.36, p = 0.042, respectively). Additionally, in those tissues, the median organ SUVmean rose significantly from baseline after the response to RLT (p ≤ 0.022), and the baseline TLP and SUVmean were significantly negatively correlated (r = −0.44, p = 0.01 and r = −0.42, p = 0.016, respectively). These observations suggest tumor sink effects with PSMA-targeted radiopharmaceuticals in the salivary glands and spleen of patients with mCRPC. Full article

Background: The available ablative procedures for the treatment of hepatic cancer have contraindications due to the heat-sink effect and the risk of thermal injuries. Electrochemotherapy (ECT) as a nonthermal approach may be utilized for the treatment of tumors adjacent to high-risk regions. We evaluated the effectiveness of ECT in a rat model. Methods: WAG/Rij rats were randomized to four groups and underwent ECT, reversible electroporation (rEP), or intravenous injection of bleomycin (BLM) eight days after subcapsular hepatic tumor implantation. The fourth group served as Sham. Tumor volume and oxygenation were measured before and five days after the treatment using ultrasound and photoacoustic imaging; thereafter, liver and tumor tissue were additionally analysed by histology and immunohistochemistry. Results: The ECT group showed a stronger reduction in tumor oxygenation compared to the rEP and BLM groups; moreover, ECT-treated tumors exhibited the lowest levels of hemoglobin concentration compared to the other groups. Histological analyses further revealed a significantly increased tumor necrosis of >85% and a reduced tumor vascularization in the ECT group compared to the rEP, BLM, and Sham groups. Conclusion: ECT is an effective approach for the treatment of hepatic tumors with necrosis rates >85% five days following treatment. Full article

Radiofrequency ablation (RFA) is a minimally invasive form of thermotherapy with great potential in cancer care, having the capability of selectively ablating tumoral masses with a surface area of several cm². When performing RFA in the proximity of a blood vessel, the heating profile changes due to heat dissipation, perfusion, and impedance changes. In this work, we provide an experimental framework for the real-time evaluation of 2D thermal maps in RFA neighboring a blood vessel; the experimental setup is based on simultaneous scanning of multiple fibers in a distributed sensing network, achieving a spatial resolution of 2.5 × 4 mm² in situ. We also demonstrate an increase of ablating potential when injecting an agarose gel in the tissue. Experimental results show that the heat-sink effect contributes to a reduction of the ablated region around 30–60% on average; however, the use of agarose significantly mitigates this effect, enlarging the ablated area by a significant amount, and ablating an even larger surface (+15%) in the absence of blood vessels. Full article

Imaging-guided percutaneous ablative treatments, such as radiofrequency ablation (RFA), cryoablation and microwave ablation (MWA), have been developed for the treatment of unresectable primary and secondary lung tumors in patients with advanced-stage disease or comorbidities contraindicating surgery. Among these therapies, MWA has recently shown promising results in the treatment of pulmonary neoplasms. The potential advantages of MWA over RFA include faster ablation times, higher intra-tumoral temperatures, larger ablation zones and lower susceptibility to the heat sink effect, resulting in greater efficacy in proximity to vascular structures. Despite encouraging results supporting its efficacy, there is a relative paucity of data in the literature regarding the role of computer tomography (CT) to monitor MWA-treated lesions, and the CT appearance of their morphologic evolution and complications. For both interventional and non-interventional radiologists, it is crucial to be familiar with the CT features of such treated lesions in order to detect incomplete therapy or recurrent disease at early stage, as well as to recognize initial signs of complications. The aim of this pictorial essay is to describe the typical CT features during follow-up of lung lesions treated with percutaneous MWA and how to interpret and differentiate them from other radiological findings, such as recurrence and complications, that are commonly encountered in this setting. Full article

Delivery of siRNAs for the treatment of tumors critically depends on the development of efficient nucleic acid carrier systems. The complexation of dendritic polymers (dendrimers) results in nanoparticles, called dendriplexes, that protect siRNA from degradation and mediate non-specific cellular uptake of siRNA. However, large siRNA doses are required for in vivo use due to accumulation of the nanoparticles in sinks such as the lung, liver, and spleen. This suggests the exploration of targeted nanoparticles for enhancing tumor cell specificity and achieving higher siRNA levels in tumors. In this work, we report on the targeted delivery of a therapeutic siRNA specific for BIRC5/Survivin in vitro and in vivo to tumor cells expressing the surface marker prostate stem cell antigen (PSCA). For this, polyplexes consisting of single-chain antibody fragments specific for PSCA conjugated to siRNA/maltose-modified poly(propylene imine) dendriplexes were used. These polyplexes were endocytosed by PSCA-positive 293T^PSCA/ffLuc and PC3^PSCA cells and caused knockdown of reporter gene firefly luciferase and Survivin expression, respectively. In a therapeutic study in PC3^PSCA xenograft-bearing mice, significant anti-tumor effects were observed upon systemic administration of the targeted polyplexes. This indicates superior anti-tumor efficacy when employing targeted delivery of Survivin-specific siRNA, based on the additive effects of siRNA-mediated Survivin knockdown in combination with scFv-mediated PSCA inhibition. Full article

Astaxanthin is a natural product gaining increasing attention due to its safety and anti-cancer properties. In this study, we investigated the mechanisms of the anti-cancer effects of astaxanthin on prostate cancer (PCa) cell lines using aggressive PCa DU145 cells. Also an instantaneous silenced cell line (si-STAT3) derived from DU145 and a control cell line (si-NK) were used for the MTT and colony formation assays to determine the role of astaxanthin in proliferation and colony formation abilities. Flow cytometry assays were used to detect the apoptosis of tumor cells. Migration and invasion assays detected the weakening of the respective abilities. Western blot and RT-PCR tests detected the levels of STAT3 protein and mRNA. Astaxanthin resulted in suppression of the proliferation of DU145 cells and the level of STAT3. The treatment of DU145 cells with astaxanthin decreased the cloning ability, increased the apoptosis percentage and weakened the abilities of migration and invasion of the cells. Furthermore, astaxanthin reduced the expression of STAT3 at protein and mRNA levels. The effects were enhanced when astaxanthin and si-STAT3 were combined. The results of animal experiments were consistent with the results in cells. Thus, astaxanthin inhibits the proliferation of DU145 cells by reducing the expression of STAT3. Full article