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Keywords = thermal ablation of cancer

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18 pages, 17724 KB  
Article
Residual Lung Cancer After Incomplete Microwave Ablation Exhibits cGAS–STING–ZEB1-Driven Malignant Progression
by Chuanfei Zhan, Yuanyuan Zhai, Tianming Chen, Xiaokang Shen, Zi Wang, Shuliang Ma and Shilin Chen
Cancers 2026, 18(16), 2594; https://doi.org/10.3390/cancers18162594 - 12 Aug 2026
Viewed by 231
Abstract
Background: Incomplete microwave ablation (iMWA) of lung cancer often leads to rapid recurrence and metastasis, yet the underlying mechanisms remain unclear. This study explored whether iMWA promotes tumor progression by activating the cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS–STING) signaling pathway and its [...] Read more.
Background: Incomplete microwave ablation (iMWA) of lung cancer often leads to rapid recurrence and metastasis, yet the underlying mechanisms remain unclear. This study explored whether iMWA promotes tumor progression by activating the cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS–STING) signaling pathway and its downstream effector ZEB1 in tumor cells. Materials and Methods: An in vivo iMWA model was established in nude mice bearing H1650 lung tumors, and an in vitro sublethal heat treatment model was used to mimic incomplete ablation. Transcriptomic profiling, molecular assays and functional analyses assessed cellular behavior and signaling activity changes post-iMWA; genetic and pharmacologic interventions modulated STING signaling and autophagy. Results: Post-iMWA residual cells exhibited enhanced proliferation and invasion. Thermal injury induced necrosis and inhibited mitophagy, causing cytosolic mtDNA accumulation that activated the intrinsic cGAS–STING pathway. This upregulation of ZEB1 drove epithelial–mesenchymal transition and dissemination. Notably, silencing STING or ZEB1, or pharmacologically restoring autophagy, significantly suppressed tumor growth and metastasis. Conclusions: iMWA drives malignant progression of lung cancer through an mtDNA–cGAS–STING–ZEB1 signaling axis. Targeting this pathway—by inhibiting STING or enhancing autophagy—may represent a promising therapeutic strategy to mitigate recurrence and metastasis following microwave ablation. Full article
(This article belongs to the Section Molecular Cancer Biology)
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27 pages, 5475 KB  
Review
Calcium-Orchestrated Vascular Collapse in Cancer Therapy: Mechanisms, Nanotherapeutic Platforms, and Translational Perspectives
by Fatima Zahra Kamal, Radu Lefter, Vasile Burlui, Alin Stelian Ciobîcă, Gabrielle Dăscălescu, Said Rammali, Andrei Luca, Ancuța Andreea Miler, Hina Alim, Otilia Novac, Bouchaib Bencharki and Bogdan Novac
Cancers 2026, 18(16), 2592; https://doi.org/10.3390/cancers18162592 - 12 Aug 2026
Viewed by 229
Abstract
Cancer therapy is increasingly focused on manipulating the tumor microenvironment rather than directly eradicating malignant cells. Vascular-targeting strategies are emerging, and calcium-mediated vascular disruption is an exciting approach through which rapid and irreversible blood flow shutdown can be achieved. Here, we overview the [...] Read more.
Cancer therapy is increasingly focused on manipulating the tumor microenvironment rather than directly eradicating malignant cells. Vascular-targeting strategies are emerging, and calcium-mediated vascular disruption is an exciting approach through which rapid and irreversible blood flow shutdown can be achieved. Here, we overview the molecular and physiological basis of calcium signaling in vascular homeostasis and outline how unregulated calcium dysfunctions in endothelial cells compromise their functionality and represent therapeutic opportunities. Elevation of intracellular calcium concentrations in endothelial cells promotes their dysfunction, coagulation, mitochondrial collapse, oxidative stress, and ultimately apoptosis, resulting in catastrophic vascular depletion and secondary necrosis that follows such collapse. A promising area of calcium-mediated attack is the emergence of exciting nanotechnologies that result in the development of calcium phosphate, calcium carbonate, and calcium peroxide nanoparticles, exploiting the enhanced permeability and retention effect of nanoparticle therapeutics to achieve selective tumor accumulation and controlled calcium release. Indeed, hybrid therapeutic platforms that couple calcium dysregulation with chemotherapy, photodynamic therapy, sonodynamic therapy, immunotherapy, or thermal ablation can exhibit pronounced antitumor effects through synergistic means. There is good preclinical evidence for the feasibility of vascular collapse mediated via calcium dysregulation. The transition of calcium to the clinic faces hurdles in relation to biosafety, how to achieve precise delivery, pharmacokinetics, and regulatory harmonization. Compared to traditional vascular disrupting agents and anti-angiogenic therapies, calcium modalities can provide rapid occlusion of vessels, are less prone to resistance development, and potentially have less systemic toxicity. Overall, calcium-mediated vascular collapse is thus an exciting next-generation technology for the vascular-targeted treatment of cancer, and likely to play an important role in precision oncology therapeutics. Full article
(This article belongs to the Section Cancer Drug Development)
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17 pages, 3605 KB  
Article
Safe and Effective Histotripsy Ablation of Human Liver Tumors in a Genetically Modified Porcine Model
by Tamalika Paul, Jessica Gannon, Manali Powar, Cora Youngs, Cassandra S. Poole, Carley M. Elliott, Mackenzie K. Woolls, Khan Imran Mohammad, Sherrie Clark-Deener, Christopher Byron, Michael Edwards, Sheryl Coutermarsh-Ott, Kristin Eden, Kiho Lee, Timothy J. Ziemlewicz, Eli Vlaisavljevich and Irving C. Allen
Cancers 2026, 18(15), 2432; https://doi.org/10.3390/cancers18152432 - 29 Jul 2026
Viewed by 498
Abstract
Background: Liver cancers are a major cause of morbidity and mortality in patients where effective, non-invasive treatment options remain limited. Objective: Histotripsy is a non-invasive, non-thermal, image-guided focused ultrasound method of ablation that mechanically disrupts cells and offers a range of potential advantages [...] Read more.
Background: Liver cancers are a major cause of morbidity and mortality in patients where effective, non-invasive treatment options remain limited. Objective: Histotripsy is a non-invasive, non-thermal, image-guided focused ultrasound method of ablation that mechanically disrupts cells and offers a range of potential advantages over other ablation modalities. The lack of physiologically and anatomically relevant animal models of human liver cancer has significantly hindered biomedical device development, including histotripsy. Methods: To address these limitations, we developed a clinically relevant large animal orthotopic, dual-tumor model of human liver cancer and utilized these unique animals to evaluate the safety and efficacy of histotripsy. Here, we utilized immunocompromised pigs with genetic modifications in their IL-2RG and RAG2 genes and orthotopically engrafted human hepatocellular carcinoma (HepG2/C3A) and pancreatic adenocarcinoma (Panc-1) cells within the liver. The models were designed to recapitulate primary and metastatic liver tumor phenotypes. Results: Histotripsy enabled real-time visualization of the treatment by the formation of bubble clouds and accurate targeting of the lesions. Histological analysis confirmed the engraftment of tumor cells and the ablation of targeted tissue. Serum biomarkers demonstrated no significant differences in bilirubin, ALT, ALKP, or CK post-treatment, suggesting that histotripsy treatment was well tolerated with minimal hepatic dysfunction or hepatocellular injury. Conclusions: These findings establish a novel, clinically relevant porcine model of primary and metastatic liver tumors and demonstrate the safety and feasibility of using this model for evaluating histotripsy as a noninvasive modality for precise tumor ablation. Full article
(This article belongs to the Special Issue Ultrasound for Cancer Therapy)
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21 pages, 8345 KB  
Review
Thermal Ablation for Colorectal Liver Metastases: Current Evidence and Future Horizons
by Xinliang Liu, Wenlong Qiu, Zhiguang Hu and Qian Liu
Diagnostics 2026, 16(14), 2239; https://doi.org/10.3390/diagnostics16142239 - 17 Jul 2026
Viewed by 517
Abstract
Liver metastasis constitutes the principal cause of mortality in colorectal cancer, with about 50% of patients developing liver metastasis during disease progression. While surgical resection remains the cornerstone of curative-intent treatment, thermal ablation is rapidly reshaping the landscape of local tumor control in [...] Read more.
Liver metastasis constitutes the principal cause of mortality in colorectal cancer, with about 50% of patients developing liver metastasis during disease progression. While surgical resection remains the cornerstone of curative-intent treatment, thermal ablation is rapidly reshaping the landscape of local tumor control in well-selected individuals. This comprehensive review analyzes the evolving role of thermal ablation in the management of resectable, unresectable, and recurrent disease, with the aim of establishing contemporary best practices and identifying critical frontiers for future research. Full article
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20 pages, 2514 KB  
Review
Nanosecond Electric Pulses as a Novel In Situ Vaccination Strategy for Cancer Treatment: Mechanisms, Challenges and Prospects
by Siqi Guo
Vaccines 2026, 14(7), 607; https://doi.org/10.3390/vaccines14070607 - 10 Jul 2026
Viewed by 530
Abstract
Nanosecond electric pulses (nsEPs) are an emerging pulsed-power technology with unique bioelectric characteristics distinct from conventional long-pulse electroporation. As a tunable physical modality, nsEPs can modulate intracellular structures, membrane dynamics, and signaling pathways. Increasing evidence supports nsEPs as a promising non-thermal tumor ablation [...] Read more.
Nanosecond electric pulses (nsEPs) are an emerging pulsed-power technology with unique bioelectric characteristics distinct from conventional long-pulse electroporation. As a tunable physical modality, nsEPs can modulate intracellular structures, membrane dynamics, and signaling pathways. Increasing evidence supports nsEPs as a promising non-thermal tumor ablation approach due to their high spatial precision, preservation of critical tissue structures, and minimal adverse effects. One of the most significant discoveries associated with nsEP tumor ablation is the induction of potent systemic antitumor immunity, particularly in situ vaccination (ISV) effects and, in some cases, abscopal effects against distant untreated tumors. Substantial evidence demonstrates that nsEPs can function as authentic immunogenic cell death (ICD) inducers by promoting the release of damage-associated molecular patterns (DAMPs), including calreticulin (CRT), ATP, and HMGB1. These events facilitate dendritic cell activation, antigen presentation, and the generation of long-term antitumor T-cell immunity. In addition to enhancing tumor immunogenicity, nsEPs profoundly remodel the tumor microenvironment (TME), including disruption of tumor vasculature, reduction in immunosuppressive cell populations, and alteration of stromal components. Emerging studies further suggest that nsEPs act as electric metabolic modulators capable of influencing mitochondrial function, calcium signaling, and metabolism-associated signaling pathways. Current evidence indicates that the immunological outcomes induced by nsEPs are highly dependent on pulse parameters, waveform characteristics, and tumor type. Despite its considerable therapeutic promise, the development of nsEP-induced ISV immunotherapy faces several important challenges, including standardization and optimization of pulse protocols, identification of critical molecular and cellular targets, and clarification of tumor- and cell-type-specific responses. Addressing these challenges through multidisciplinary collaboration and advanced technologies, including multi-omics, spatial analysis, and computational modeling, may accelerate the development of next-generation bioelectric immunotherapies for cancer treatment. Full article
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13 pages, 7297 KB  
Article
Morphologic, Immunohistochemical, and Molecular Features of Laser-Ablated Thyroid Nodules: Diagnostic Pitfalls and Differential Diagnosis with Thyroid Carcinoma
by Pietro Tralongo, Fernanda Russotto, Valeria Zuccalà, Vincenzo Fiorentino, Marina Gloria Micali, Mariausilia Franchina, Ludovica Pepe, Walter Giordano, Gabriele Ricciardi, Mariagiovanna Ballato, Emanuela Germanà, Emilia Magliolo, Serenella Ristagno, Esther Diana Rossi, Maurizio Martini and Guido Fadda
Int. J. Mol. Sci. 2026, 27(13), 5880; https://doi.org/10.3390/ijms27135880 - 30 Jun 2026
Viewed by 439
Abstract
Thermal ablation (TA) is an increasingly adopted minimally invasive treatment for benign thyroid nodules. However, TA induces marked histological alterations that may simulate thyroid malignancy, creating significant diagnostic pitfalls for pathologists. The present study expands our previous institutional series and further characterizes the [...] Read more.
Thermal ablation (TA) is an increasingly adopted minimally invasive treatment for benign thyroid nodules. However, TA induces marked histological alterations that may simulate thyroid malignancy, creating significant diagnostic pitfalls for pathologists. The present study expands our previous institutional series and further characterizes the morphologic, immunohistochemical, and molecular features of thermally ablated thyroid nodules in order to refine the differential diagnosis with thyroid carcinoma. Fourteen surgically excised thyroid nodules previously treated with laser thermal ablation were retrospectively analyzed. Histopathological evaluation focused on architectural changes, nuclear atypia, capsule alterations, degenerative phenomena, and evidence of invasion. Immunohistochemical analysis included galectin-3 (Gal-3), HBME-1, BRAF V600E, p53, and Ki-67. In addition, molecular profiling for the principal thyroid cancer-related alterations, including BRAF, RAS family genes, TERT promoter mutations, PIK3CA alterations, and RET rearrangements, was performed using targeted next-generation sequencing. All nodules showed treatment-related reactive and degenerative changes, including fibrosis/sclerosis, subcapsular hemorrhage, focal oncocytic metaplasia, and architectural distortion. No true capsular or vascular invasion was identified. Immunohistochemically, all cases were negative for Gal-3 and BRAF V600E, while HBME-1 expression was absent or only focally weak. Ki-67 proliferative activity remained consistently low (<3%) in all cases. Molecular analyses did not identify pathogenic alterations involving BRAF, RAS, TERT promoter, PIK3CA, or RET genes in any case. Thermal ablation induces reproducible reactive and degenerative histologic alterations that may closely mimic follicular or papillary thyroid neoplasms. The absence of malignancy-associated immunohistochemical and molecular alterations strongly supports the benign nature of these lesions and highlights the importance of an integrated morphologic, immunohistochemical, and molecular diagnostic approach in challenging post-ablation specimens. Thermally ablated thyroid nodules may display significant pseudo-neoplastic changes that can lead to overdiagnosis of carcinoma. Awareness of these treatment-related alterations, combined with immunohistochemical and molecular profiling, represents a reliable strategy to distinguish reactive post-ablation changes from true thyroid malignancy and to avoid inappropriate clinical management. Full article
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11 pages, 759 KB  
Article
Thermal Ablation of Breast Cancer Liver Metastases Is Associated with Durable Local Control and Chemotherapy-Free Intervals in Selected Patients
by Niaz Ahmed, Alicia Okines, Sophie McGrath, Marina Parton, Emma Kipps, Nicholas Turner, Edward Johnston, Stephen Johnston and Nicos Fotiadis
Cancers 2026, 18(12), 1997; https://doi.org/10.3390/cancers18121997 - 19 Jun 2026
Viewed by 580
Abstract
Background/Objectives: In selected patients with oligometastatic breast cancer liver metastases (BCLM), liver-directed therapies may provide durable local control and may delay escalation of systemic therapy. This study reports a single-center experience of percutaneous thermal ablation (radiofrequency ablation [RFA] or microwave ablation [MWA]) [...] Read more.
Background/Objectives: In selected patients with oligometastatic breast cancer liver metastases (BCLM), liver-directed therapies may provide durable local control and may delay escalation of systemic therapy. This study reports a single-center experience of percutaneous thermal ablation (radiofrequency ablation [RFA] or microwave ablation [MWA]) for BCLM, including conventional oncologic outcomes and therapy-based endpoints. Methods: This retrospective cohort included consecutive patients treated with percutaneous ablation for BCLM following multidisciplinary team approval between 2005 and 2025. Outcomes were defined according to the Society of Interventional Oncology (SIO) and DATECAN consensus terminology. Lesion-level outcomes included primary/secondary technique efficacy and local tumor progression-free survival (LTPFS). Patient-level outcomes included progression-free survival (PFS), overall survival (OS), time to change in systemic therapy (TTCST) and chemotherapy-free survival (CFS). Kaplan–Meier and Cox regression analyses were performed. Results: Forty-six patients underwent 58 ablation sessions treating 80 metastases (median tumor size 19 mm, interquartile range [IQR] 13–27 mm). Primary and secondary technique efficacy were 95% (76/80) and 99% (79/80), respectively. Major complications occurred in 2/58 sessions (3%). Local tumor progression occurred in 16/79 tumors (20%) after a median follow-up of 28 months; LTPFS rates at 1, 3 and 5 years were 84%, 75% and 75%, respectively. Median OS was 44 months (1-, 3- and 5-year OS 94%, 58%, and 40%), and median PFS was 8.3 months. Median TTCST was 13 months, and median CFS was 16.4 months. Triple-negative disease was associated with worse LTPFS and shorter CFS. Oligopersistent disease was associated with improved PFS compared with oligoprogression. Conclusions: In this selected cohort, percutaneous thermal ablation for BCLM achieved high technique efficacy, durable local control and low major complication rates. Therapy-based endpoints suggest a clinically meaningful interval without systemic therapy escalation in appropriately selected patients, although comparative studies are needed to quantify the incremental benefit. Full article
(This article belongs to the Section Cancer Therapy)
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54 pages, 85092 KB  
Review
Advances and Prospects in MOF-Based Platforms for Tumor Hyperthermia
by Diyi Feng and Liqin Ge
Bioengineering 2026, 13(6), 693; https://doi.org/10.3390/bioengineering13060693 - 17 Jun 2026
Viewed by 768
Abstract
Metal-organic framework (MOF)-based materials have become promising platforms for tumor hyperthermia by integrating energy conversion, tumor microenvironment regulation, and multimodal therapy within programmable porous structures. This review summarizes recent advances in intrinsic MOFs, MOF composites, and MOF-derived materials for photothermal therapy, microwave hyperthermia, [...] Read more.
Metal-organic framework (MOF)-based materials have become promising platforms for tumor hyperthermia by integrating energy conversion, tumor microenvironment regulation, and multimodal therapy within programmable porous structures. This review summarizes recent advances in intrinsic MOFs, MOF composites, and MOF-derived materials for photothermal therapy, microwave hyperthermia, and magnetic hyperthermia. The reviewed studies show that high-valence metal MOFs mainly provide stable and modifiable frameworks, whereas transition-metal, magnetic, and multimetallic MOFs contribute to redox regulation, ROS generation, magnetic response, and microwave energy dissipation. Beyond localized heat generation, MOF-based platforms enhance therapeutic efficacy by combining hyperthermia with chemotherapy, chemodynamic therapy, metabolic intervention, immunotherapy, and imaging guidance. These integrated strategies help overcome incomplete ablation, thermotolerance, oxidative stress resistance, and tumor recurrence. However, clinical translation is still limited by insufficient standardization, uncertain degradation behavior, metal-ion safety, and inadequate thermal dose control. Future development should emphasize mechanism-oriented design, controllable composition, long-term biosafety, and image-guided thermal regulation to advance MOF-based hyperthermia toward precise and clinically relevant cancer therapy. Full article
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20 pages, 2984 KB  
Article
Myeloid Cell Targeting Strategies Show Limited Durable Activity in the Breast Cancer Tumor Microenvironment and Do Not Enhance the Activity of Thermally Ablative Focused Ultrasound
by Carly M. Van Wagoner, Lydia E. Kitelinger, Matthew R. DeWitt, Claire A. Conarroe, AeRyon Kim, Aaron B. Streit, Richard J. Price and Timothy N. J. Bullock
Cells 2026, 15(11), 1035; https://doi.org/10.3390/cells15111035 - 4 Jun 2026
Viewed by 592
Abstract
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer (BrCa), owing to its lack of targetable receptors and resistance to chemical and molecularly targeted therapeutic approaches. While chemotherapy and surgical resection remain the standard of care, these interventions have significant [...] Read more.
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer (BrCa), owing to its lack of targetable receptors and resistance to chemical and molecularly targeted therapeutic approaches. While chemotherapy and surgical resection remain the standard of care, these interventions have significant side effects and varying patient outcomes. Thermally ablative focused ultrasound (T-FUS)—a non-invasive and non-ionizing therapy that utilizes targeted acoustic energy to debulk tumors—has displayed immunomodulatory effects in BrCa. However, T-FUS as a monotherapy has had limited clinical efficacy in TNBC due to the presence of anti-inflammatory immunosuppressive myeloid cells (isMCs). We hypothesized that the elimination of isMCs or initiating tumoricidal activity from them would lead to augmented activity of T-FUS. Thus, we interrogated the ability of myeloablative chemotherapies and antibodies; myeloid recruiting chemokine receptor blockade; and TLR agonists to remodel the tumor myeloid populations. Consistent with our previous studies, we found that while myeloablative chemotherapies decreased circulating isMCs, they had little impact on intratumoral isMCs. In contrast, antibodies targeting Ly6C and Ly6G ablated intratumoral isMCs and systemic isMCs, yet their effect was transient and was accompanied by a surprising depletion of T cells. While targeting CCR2, the dominant chemokine receptor for intratumoral isMC diminished a large subset of immunosuppressive cells within the TME; it also depleted T cells and dendritic cells. Contrary to previous studies, TLR stimulation failed to repolarize myeloid cells into a pro-inflammatory, tumoricidal phenotype but did lead to their depletion from the tumor microenvironment (TME) and mobilization of conventional dendritic cells to the draining lymph nodes. We therefore hypothesized that combining isMC depletion and TLR-driven immune activation would enhance FUS efficacy; however, this combinatorial regimen did not enhance overall survival or control tumor volume after T-FUS treatment. Thus, the BrCa TME is highly resistant to approaches intended to remodel the myeloid cell component which fail to synergize with T-FUS-mediated tumor ablation. Full article
(This article belongs to the Section Cellular Immunology)
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16 pages, 4660 KB  
Article
Image-Guided Thermal Ablation of Stage 1 Single and Multiple Primary Lung Carcinoma: Five-Year Outcomes
by Jamie E. Clarke, Noor Jahanshahi, Bianca Villegas, Grace Hyun J. Kim, Soheil Kooraki, Matthew Quirk, Scott Genshaft, Robert D. Suh and Fereidoun Abtin
Med. Sci. 2026, 14(2), 272; https://doi.org/10.3390/medsci14020272 - 27 May 2026
Viewed by 498
Abstract
Background: Image-guided thermal ablation has been used for the treatment of primary lung carcinoma but its use in the treatment of multiple lung carcinoma and effects on survival have not been well established. Objective: This study compares the long-term survival metrics for stage [...] Read more.
Background: Image-guided thermal ablation has been used for the treatment of primary lung carcinoma but its use in the treatment of multiple lung carcinoma and effects on survival have not been well established. Objective: This study compares the long-term survival metrics for stage 1 single primary lung cancer and multiple primary lung cancer (MPLC) in patients treated with image-guided thermal ablation (IGTA). Methods: A retrospective institutional review included 37 NSCLC patients (mean age 71.6 ± 8.8 years) with ≥5 years follow-up. In total, 119 IGTA procedures were performed. Among patients with a single tumor (n = 14, 37.8%), each underwent a single ablation session. In contrast, patients with MPLC (n = 23, 62.2%) underwent 88 ablation sessions to treat 105 tumors. Data included demographics, tumor features, procedural details, safety, adverse events, and outcomes. Primary endpoints were 5-year overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CSS). Results: All ablations were completed successfully. Severe AEs occurred in 5.8% (7/119) of the ablations and were limited to pneumothorax requiring chest tube placement with hospitalization. At the time of ablation, individual nodules were staged at T1A = 46 (38.7%), T1B = 54 (45.4%), T1C = 16 (13.5%) and T2A = 3 (2.5%). Local recurrence was observed in 4/119 (3.3%) ablated tumors, all at stage T1B, and all were retreated with ablation. The 5-year OS was better for patients with MPLC at 85.6% compared to patients with a single tumor at 35.7% (HR = 0.14, p = 0.003, 95% CI: 0.037, 0.51). The 5-year OS for tumors based on T classification for T1A, T1B, TIC and T2A was 71.4%, 66.8%,66.7% and 0%. The 5-year PFS was 77.4% for patients with MPLC compared to 35.7% for patients with single primary lung cancer (HR = 0.25, p = 0.014, 95% CI: 0.084, 0.76). The 5-year CSS was 95.2% for patients with MPLC compared to 83.1% for patients with single primary lung cancer (HR = 0.21, p = 0.16, 95% CI: 0.018, 2.33). Conclusions: IGTA is an effective and safe treatment for patients with stage 1 single primary lung cancer and MPLC with limited local recurrence. Tumor size up to 3 cm did not have significant impact on survival. Overall survival was improved in patients with MPLC compared to those with single NSCLC. Clinical Impact: IGTA can be safely performed in patients with single primary lung cancer and MPLC, with limited local recurrence rate. Highlights: Key Findings: IGTA effectively treats patients with stage 1 single primary lung cancer and MPLC, with 3.3% recurrence, which can be retreated with ablation. The five-year OS was higher in patients with MPLC (85.6%) versus those with single lung cancer (35.7%, p = 0.003). OS by T classification: 71.4% for T1A, 66.8% for T1B, 66.7% for TIC, and 0% for T2A. Importance: IGTA effectively treats patients with single primary lung cancer and MPLC with low recurrence. Tumor size < 3 cm showed no impact on overall survival. Full article
(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)
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38 pages, 988 KB  
Review
The Potential and Challenges of Focused Ultrasound-Mediated Therapies in the Management of Liver and Biliary Tract Cancers
by Mira Florea, Viorica Nagy, Paul Milan Kubelac, Adrian Bartos, Delia Dima, Rares Potcoava Buiga and Monica Lupsor-Platon
Cancers 2026, 18(10), 1654; https://doi.org/10.3390/cancers18101654 - 20 May 2026
Viewed by 828
Abstract
Focused ultrasound (FUS)-mediated therapies have evolved with the advent of modern ultrasound-guided technology and MRI imaging, moving from their initial use as thermal ablation to a multifunctional platform for thermal and non-thermal ablation, immunomodulation, and targeted drug delivery. This narrative review explores the [...] Read more.
Focused ultrasound (FUS)-mediated therapies have evolved with the advent of modern ultrasound-guided technology and MRI imaging, moving from their initial use as thermal ablation to a multifunctional platform for thermal and non-thermal ablation, immunomodulation, and targeted drug delivery. This narrative review explores the potential, limitations, and challenges of ablative high-intensity focused ultrasound (HIFU) therapies: HIFU thermal ablation and non-thermal ablation, histotripsy, as well as non-ablative low-intensity focused ultrasound (LIFU) applications in the management of hepatobiliary cancers. HIFU and histotripsy are reviewed as alternative or complementary treatment options in liver tumors, as well as their potential as bridging therapy. Histotripsy is addressed as a theranostic tool, not only by combining ablation with real-time ultrasound imaging guidance, but also by integrating it with sonobiopsy. It facilitates a liquid sonobiopsy of the ablated tumor by releasing intact tumor antigens and damage-associated molecular patterns, leading to potential molecular profiling. LIFU-induced targeted drug delivery (sono-chemotherapy), sonodynamic therapy, radiosensitization, immunomodulation of the immunosuppressive tumor microenvironment (sono-immunotherapy), and the potential to enhance the effect of immune checkpoint inhibitors in these malignancies are discussed. Since FUS-assisted procedures exhibit dual actions through therapeutic functionality associated with intra- and post-procedural ultrasound imaging guidance, they could have value as a theranostic tool in hepatobiliary interventional oncology. Although promising, the available clinical evidence for FUS-mediated therapies in hepatobiliary malignancies consists predominantly of early-stage feasibility studies, retrospective observational cohorts, and non-randomized comparative analyses. Further studies focused on standardized protocols, validation through large-scale, multicenter, prospective randomized clinical trials comparing FUS-based therapies with established treatments, and long-term follow-up of oncological efficacy could define their future role in multimodal oncological strategies. Full article
(This article belongs to the Special Issue Application of Ultrasound in Cancer Diagnosis and Treatment)
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13 pages, 2483 KB  
Review
See and Strike: A Dual-Force Paradigm for Real-Time Lung Cancer Diagnosis and Non-Thermal Ablation
by Jaskiran Khosa and Roy J. Cho
Diagnostics 2026, 16(10), 1553; https://doi.org/10.3390/diagnostics16101553 - 20 May 2026
Viewed by 739
Abstract
Lung cancer remains the leading cause of cancer-related mortality worldwide despite advances in screening, navigational bronchoscopy, and systemic therapies. Diagnostic and therapeutic limitations persist, including uncertainty regarding intraprocedural tissue adequacy during biopsy sampling and constraints of existing ablative modalities for tumors located near [...] Read more.
Lung cancer remains the leading cause of cancer-related mortality worldwide despite advances in screening, navigational bronchoscopy, and systemic therapies. Diagnostic and therapeutic limitations persist, including uncertainty regarding intraprocedural tissue adequacy during biopsy sampling and constraints of existing ablative modalities for tumors located near critical thoracic structures. This review examines two emerging technologies: Full-Field Optical Coherence Tomography-based Dynamic Cell Imaging (DCI) and monopolar biphasic Pulsed Electric Field (PEF) ablation as complementary emerging technologies that may address these gaps. The Van Gogh™ Microscopy System (CellTivity Scientific, Inc.) utilizes DCI to enable real-time visualization of cellular metabolic activity without tissue destruction, providing functional information regarding tissue viability and microstructural morphology. The Aliya® PEF ablation system (Galvanize Therapeutics, Inc.) delivers biphasic high-voltage electrical pulses that induce non-thermal tumor cell death while preserving extracellular matrix architecture, potentially allowing treatment near sensitive thoracic structures such as airways, vasculature, and pleura. Early preclinical studies and initial clinical experience suggest that DCI can facilitate rapid intraprocedural assessment of biopsy adequacy, while PEF ablation may provide reproducible focal tumor destruction with a favorable safety profile near critical structures. Although the current evidence base remains limited to early-phase studies and feasibility trials, the convergence of real-time biologic tissue assessment with structurally preserving ablation technologies introduces the possibility of integrating diagnostic confirmation and local therapy within a single procedural workflow. This review summarizes the mechanistic rationale, emerging evidence, and potential clinical applications of these technologies and proposes a conceptual “See and Strike” framework within these two emerging technologies. The methodological limitations, workflow considerations, and future research directions required to validate this approach are also discussed. Prospective multicenter trials and long-term oncologic outcomes will be necessary before widespread clinical adoption. Full article
(This article belongs to the Special Issue Advancements and Innovations in the Diagnosis of Lung Cancer)
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18 pages, 886 KB  
Review
Focal Therapy for Prostate Cancer: State of the Art, Physical Principles, Potentials, and Challenges
by Luca Orecchia, Simone Steffani, Andrea Micillo, Roberto Miano, Eric Walser and Guglielmo Manenti
Cancers 2026, 18(10), 1523; https://doi.org/10.3390/cancers18101523 - 9 May 2026
Cited by 2 | Viewed by 1420
Abstract
Background: The management of localized prostate cancer (PCa) suffers from the dilemma between the overtreatment associated with radical surgery and the uncertainty of active surveillance, highlighting a significant therapeutic gap specifically for intermediate-risk patients and selected low-risk patients. Focal therapy (FT) emerges as [...] Read more.
Background: The management of localized prostate cancer (PCa) suffers from the dilemma between the overtreatment associated with radical surgery and the uncertainty of active surveillance, highlighting a significant therapeutic gap specifically for intermediate-risk patients and selected low-risk patients. Focal therapy (FT) emerges as an advanced technological solution to balance rigorous oncological control with anatomical and functional preservation. Methods: A narrative review of the literature was conducted to analyze the physical principles underlying various ablative energies (thermal, cryogenic, and non-thermal) as well as radiation-based focal approaches. The review examines the oncological rationale of targeted ablation, recent innovations in imaging, and the expanding clinical scenarios for FT application. Results: Evidence supports the oncological rationale of “Index Lesion” ablation as a targeted curative strategy for clinically significant disease, rather than merely a palliative one. The review highlights the emerging concept of “pushing the disease” and demonstrates the valuable role of salvage focal therapy in the setting of radio-recurrent carcinoma. Furthermore, recent innovations in multiparametric magnetic resonance imaging (mpMRI) and fusion systems have significantly refined patient selection, rendering this minimally invasive approach highly targeted. Conclusions: The current barrier to the universal adoption of focal therapy is the lack of a standardized consensus on the definitions of therapeutic failure and the inadequacy of traditional PSA-based criteria. However, evidence suggests that FT represents a promising, organ-sparing alternative for carefully selected patients with localized PCa, though long-term comparative data are still required. Full article
(This article belongs to the Special Issue Minimally Invasive Therapies in Urologic Cancers)
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14 pages, 2838 KB  
Article
Nakagami Statistics-Based Parametric Thermoacoustic Imaging for Assessment of Liver Microwave Ablation
by Ling Song, Lian Feng, Jieni Song, Wanting Yang, Zhenru Wu, Wenwu Ling, Lin Huang and Yan Luo
Bioengineering 2026, 13(5), 537; https://doi.org/10.3390/bioengineering13050537 - 6 May 2026
Viewed by 1361
Abstract
Thermal ablation is an effective treatment for primary liver cancer, but intraoperative assessment of ablation efficacy remains a clinical challenge. Microwave-induced thermoacoustic imaging (TAI) offers high tissue contrast based on dielectric properties, whereas conventional delay-and-sum reconstruction often yields limited contrast between ablated and [...] Read more.
Thermal ablation is an effective treatment for primary liver cancer, but intraoperative assessment of ablation efficacy remains a clinical challenge. Microwave-induced thermoacoustic imaging (TAI) offers high tissue contrast based on dielectric properties, whereas conventional delay-and-sum reconstruction often yields limited contrast between ablated and normal tissue. To improve the contrast, we present a post-processing parametric imaging method that applies Nakagami statistics to thermoacoustic signal envelopes. The Nakagami shape parameter m is sensitive to thermal-ablation-induced alterations in tissue microstructural features. This work represents a new attempt to extract parametric images from thermoacoustic signal envelopes for intraoperative ablation assessment. In vitro and in vivo experiments were conducted to evaluate this Nakagami-based approach. Compared with conventional TAI, Nakagami images exhibited markedly improved contrast between the ablation zone and normal tissue. Quantitative analysis using pathological images as the gold standard demonstrated higher accuracy for Nakagami-based TAI across all measurements: 91.08% vs. 85.22% (in vitro diameter), 86.76% vs. 74.50% (in vitro area), 85.44% vs. 76.52% (in vivo diameter), and 79.22% vs. 72.72% (in vivo area). These findings suggest that Nakagami statistics-based TAI improves ablation zone characterization by capturing tissue microstructural information, showing potential as a tool for intraoperative assessment of liver ablation efficacy. Full article
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Article
Pulsed Electric Field Ablation for Advanced Lung and Oligometastatic Disease: A Retrospective Study of 32 Consecutive Patients in a Community Hospital Setting
by Varun Roperia and Justin Thomas
Cancers 2026, 18(9), 1459; https://doi.org/10.3390/cancers18091459 - 1 May 2026
Viewed by 1312
Abstract
Background/Objectives: Pulsed Electric Field (PEF) therapy is a non-thermal ablation technique that induces immunogenic cell death through high-voltage, short-duration electrical pulses. This may enhance antitumor immunity by releasing intact tumor antigens and potentially generating abscopal effects. We report early outcomes in 32 patients [...] Read more.
Background/Objectives: Pulsed Electric Field (PEF) therapy is a non-thermal ablation technique that induces immunogenic cell death through high-voltage, short-duration electrical pulses. This may enhance antitumor immunity by releasing intact tumor antigens and potentially generating abscopal effects. We report early outcomes in 32 patients with primary lung cancer or lung oligometastases treated with PEF at a community hospital, with a median (IQR) follow-up of 180.5 (158–207) days. Methods: This retrospective study collected demographics, cancer type, treatment response, and outcomes for patients undergoing PEF ablation. Tumor response was assessed using Sum of Longest Dimensions per RECIST 1.1 to classify progressive disease, stable disease, partial response, or complete response. Volumetric changes were additionally analyzed using RECIST 1.1 percentage thresholds applied to change in volume. Results: At initial 3-month follow-up, 26 of 32 patients demonstrated stable disease, partial response, or complete response, suggesting an 81.25% disease control rate/clinical benefit rate among this cohort. Among patients with Stage III–IV disease, 27.6% (8/29) showed radiographic evidence of a possible abscopal response. At 6 months, 24 of 32 patients remained alive and evaluable, with 62.5% (20/32) maintaining stable disease, partial response, or complete response. Conclusions: Despite patients having progressive disease on systemic therapy before PEF, early outcomes post-ablation suggest favorable local control and potential immunologic benefit. Patients with early-stage disease not receiving systemic therapy also showed excellent local response. Patients tolerated therapy very well. Clinical benefit was observed in 81.25% of patients at 3 months and 62.5% at 6 months, with radiographic evidence of possible abscopal responses in 27.6% of advanced-stage patients, supporting further exploration of the immunogenic potential of PEF demonstrated in preclinical and emerging clinical studies. Full article
(This article belongs to the Section Methods and Technologies Development)
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