Cancer Ablation Research Articles

CT-guided local ablative interventions

Applicator-based local ablations under computed tomography (CT) guidance for the treatment of malignant tumors have found their way into clinical routine. The basic principles of the different ablation technologies and their specific clinical field of application are described. Acomprehensive literature review regarding applicator-based ablation techniques was carried out. Radiofrequency (RFA) and microwave ablation (MWA) represent two image-guided hyperthermal treatment modalities that have been established for the treatment of primary and secondary liver malignancies. In addition, both techniques are also applied for local ablative therapy of lung- and kidney tumors. Cryoablation is mainly used for the local ablation of T1 kidney cancer and due to its intrinsic analgetic characteristics for application in the musculoskeletal system. Nonresectable pancreatic tumors and centrally located liver malignancies can be treated with irreversible electroporation. This nonthermal ablation modality preserves the structure of the extracellular matrix including blood vessels and ducts. Technical advancements in the field of CT-guided interventions include the use of robotics, different tracking and navigation technologies and the use of augmented reality with the goal to achieve higher precision, shorter intervention time and thereby reduce radiation exposure. Percutaneous ablation techniques under CT guidance are an essential part of interventional radiology and they are suited for local treatment of malignancies in most organ systems.

Biopsy Assessment of Oncologic Control 3 Years Following Primary Partial Gland Cryoablation: A Prospective Cohort Study of Men With Intermediate-risk Prostate Cancer.

We evaluated 3-year oncologic outcomes following primary partial gland cryoablation. Men with unilateral intermediate-risk prostate cancer undergoing primary partial gland cryoablation since March 2017 enrolled in a prospective outcome registry. The postablation protocol for all men included surveillance prostate biopsy at 2 years postablation and reflex prostate biopsy for cases with high suspicion of recurrence (eg, progressive rise in PSA). Recurrence of clinically significant prostate cancer was defined as any Gleason grade group ≥2 disease on postablation biopsy. Freedom from failure represented no whole gland salvage treatment, metastatic prostate cancer, or prostate cancer mortality. Freedom from recurrence and freedom from failure were characterized using nonparametric maximum likelihood estimators. A total of 132 men had at least 24 months of follow-up data. Biopsies identified clinically significant prostate cancer in 12 men. At 36 months, model-estimated rates of freedom from recurrence of in-field, out-of-field, and overall clinically significant cancer were 97% (95% CI: 92-100), 87% (95% CI: 80-94), and 86% (95% CI: 78-93), respectively. The model-estimated proportion with freedom from failure at 36 months was 97% (95% CI: 93-100). The low in-field cancer detection rate at 3 years indicates successful ablation of localized cancers. Conversely, our observed out-of-field detection rate highlights the need for continued surveillance following partial gland cryoablation. Many of these recurrences exhibited very low volume of clinically significant disease below the detection threshold of multiparametric MRI, suggesting a limited role for multiparametric MRI in detecting clinically significant recurrences at 2 years. These findings emphasize the need for long-term surveillance and identification of predictors of clinically significant prostate cancer recurrences to guide biopsy timing.

Radiofrequency ablation of lung metastases of colorectal cancer: could early radiomics analysis of the ablation zone help detect local tumor progression?

To determine whether radiomics data can predict local tumor progression (LTP) following radiofrequency ablation (RFA) of colorectal cancer (CRC) lung metastases on the first revaluation chest CT. This case-control single-center retrospective study included 95 distinct lung metastases treated by RFA (in 39 patients, median age: 63.1 years) with a contrast-enhanced CT-scan performed 3 months after RFA. Forty-eight radiomics features (RFs) were extracted from the 3D-segmentation of the ablation zone. Several supervised machine-learning algorithms were trained in 10-fold cross-validation on reproducible RFs to predict LTP, with/without denoising CT-scans. An unsupervised classification based on reproducible RFs was built with k-means algorithm. There were 20/95 (26.7%) relapses within a median delay of 10 months. The best model was a stepwise logistic regression on raw CT-scans. Its cross-validated performances were: AUROC = 0.72 (0.58-0.86), area under the Precision-Recall curve (AUPRC) = 0.44. Cross-validated balanced-accuracy, sensitivity and specificity were 0.59, 0.25 and 0.93, respectively, using p = 0.5 to dichotomize the model predicted probabilities (vs 0.71, 0.70 and 0.72, respectively using p = 0.188 according to Youden index). The unsupervised approach identified two clusters, which were not associated with LTP (p = 0.8211) but with the occurrence of per-RFA intra-alveolar hemorrhage, post-RFA cavitations and fistulizations (p = 0.0150). Predictive models using RFs from the post-RFA ablation zone on the first revaluation CT-scan of CRC lung metastases seemed moderately informative regarding the occurrence of LTP. Radiomics approach on interventional radiology data is feasible. However, patterns of heterogeneity detected with RFs on early re-evaluation CT-scans seem biased by different healing processes following benign RFA complications.

Efficacy and safety of regorafenib and PD-1 combined with cryoablation in the treatment of advanced hepatocellular carcinoma after second-line targeted therapy.

e16151 Background: Targeted therapy is the most effective therapeutic approach for middle and late-stage hepatocellular carcinoma (HCC). Regorafenib or PD-1 as a second-line treatment of patients with advanced HCC has achieved good results. Argon-helium cryoablation is one commonly used method for local ablation of liver cancer. Whether systemic therapy combined with local therapy can benefit patients with advanced liver cancer is a hot topic. This study is aimed to investigate the efficacy and safety of regorafenib and PD-1 combined with cryoablation in the treatment of patients with advanced HCC after the failure of second-line targeted treatment. Methods: In this retrospective study, unresectable HCC patients received regorafenib and PD-1combined with cryoablation after the failure of second-line targeted treatment from January 2019 to December 2021 were enrolled. Depending on whether combining local therapy, patients were grouped as RP (regorafenib and PD-1), or RPC groups (regorafenib and PD-1 combined with cryoablation). Objective response rate (ORR), disease control regorafenib rate (DCR), progression free survival (PFS), and safety were recorded. The PFS was defined as the time from the first dose of RP, or from the time of using RPC until disease progression or death. Results: A total of 50 patients were reviewed, including 21 patients in RP group and 29 patients in RCP group. One patient was classified as Barcelona Clinic Liver Cancer (BCLC) stage B and 20 patients were at BCLC stage C in RP group, while one patient was at BCLC stage B and 28 patients were at BCLC stage C in RPC group. The ORR and DCR were 4.8% and 23.8% in PR group respectively, and 31.0% and 69.0% in RPC group respectively. The 6-month PFS rate of RP group and RPC group was 14.3% and 53.6% respectively. Thirteen (61.9%) and eighteen (62.1%) patients experienced adverse events (AEs) in two groups respectively. Two (9.5%) and three (10.7%) patients experienced grade 3 AEs that occurred in RP group and RPC group respectively. The most frequency AE was hand-foot-skin reaction in both groups (58.0% and 50.0%, respectively). No patient discontinued regorafenib and PD-1 due to AE in these two groups. Conclusions: Regorafenib and PD-1 combined with cryoablation showed potential anti-tumor effect and tolerance on unresectable HCC after the failure of second-line targeted treatment. [Table: see text]

EpCAM CAR T (IMC001) for the treatment of advanced GI cancers.

4034 Background: EpCAM is highly expressed in various cancer types of the GI system and at metastatic sites. It serves as a promising prognostic/predictive marker (CTC) and therapeutic target. IMC001 is an EpCAM-targeted CAR-T cell that showed promising anti-tumor activities in preclinical studies. Here, we report the results of the low and middle dosage groups in advanced gastric cancers (CT03) and GI cancers (CT04). Methods: This first-in-human, open-label trial involved two separate single-site trials. Both followed a classic 3+3 design with dose escalation of 0.3, 1 or 3 million CAR-T cells/kg after lymphodepletion chemotherapy. CT03 was an IMC001 monotherapy trial (Stage 1) for gastric cancer, while CT04 had Stage 1 and the combination with RFA or microwave ablation (Stage 2) for GI cancers. Eligible patients were those with EpCAM-positive (more than 10%) cancers who had no further standard treatment options and were ECOG 0 or 1. The objective was to assess the safety, PK/PD profile and preliminary efficacy of IMC001. Results: As of January 30, 2023, 12 patients with 6 colorectal and 6 gastric cancers had enrolled, with half receiving 0.3 million and the other half receiving 1 million cells/kg IMC001 infusion. No patient experienced DLT within the 4-week follow-up visits after infusion. All patients experienced ≥Grade 3 hematologic toxicity. One patient in the low-dose group had a SAE of immune hepatitis (Grade 3), which might have been related to cell therapy, and occurred around 11 days after the CAR-T infusion, prolonging the patient's hospitalization. Manageable CRS (Grade 1 to 3) and no ICANS were observed. Other adverse events related to cell therapy were CTCAE Stage 1-2 nausea, vomiting, asthenia, or pruritus, and these recovered quickly. Analyses of the CAR-T cells in peripheral blood revealed robust engraftment in all patients, with the peak number of CAR+ cells reaching on day 5-7 after infusion. CTC remained under the detection limit for more than 40 weeks after cell infusion. Significant elevations of serum levels of IL-6, IP-10, IFN-γ, IL-15, and MCP-1 were observed in most patients. Preliminary efficacy data showed that 2 out of 6 advanced gastric cancer patients were evaluated as PR and 3 remained SD by RECIST 1.1 at the low and middle dosages (CT03). The first PR patient received a second IMC001 infusion on week 50 and had survived for more than 60 weeks. The second PR patient underwent successful surgical removal of the stomach 28 weeks after IMC001 infusion. The CT04 trial is ongoing. Conclusions: This is the first CAR-T therapy ever tested in humans targeting the EpCAM. IMC001 showed a favorable safety profile and reasonable anti-tumor activities at the low and middle dosage levels in patients with advanced EpCAM+ GI cancers, especially in gastric cancer. In addition, our trial has successfully provided a surgical treatment opportunity after CAR-T therapy downstaging of unresectable gastric cancers. Updated data from open cohorts will be presented. Clinical trial information: NCT05028933 .

The role of surface modification in improving the effectiveness of CuS nanorods for cancer ablation therapy and antibacterial applications

We report a new methodology to synthesize CuS nanorods (CuS NRs) via hydrothermal route, and surface modified with chitosan (CS) and folic acid (FA) to demonstrate the role of surface modification in photo-thermal heat generation and cancer photo ablation therapy. The electron microscopy investigations showed the formation of rod-shaped CuS nanomaterial and the length and diameter of nanorods (NRs) were found to be ∼55 and 22 nm, respectively. The surface modification of CuS NRs was investigated by UV–Vis spectroscopy, FTIR spectroscopy, dynamic light scattering technique, and Raman spectroscopy. Without any compromise in photo-thermal heat generation, the surface modification significantly improved biocompatibility, cancer cell cytotoxicity, and anti-bacterial activity. The photothermal heat generation experiments with 808 nm laser light revealed that the temperature increase was found to be 54 ℃ for surface modified FA-CS@CuS NRs at 500 µg/mL which increased to ∼100 ℃ when the laser power intensity was increased from 0.5 to 1.5 W/cm2. The photothermal conversion efficiency (PCE) was estimated to be 38.6% for FA-CS@CuS NRs. Notably, the photothermal heat generation is significantly influenced by CuS NRs concentration and laser power intensity. The anticancer activity investigations against HCT116 cancer cells revealed enhanced cytotoxicity for cancer cells owing to synergistic effects of hyperthermia and generation of highly toxic hydroxyl radicals (·OH) induced by the release of Cu2+ions. The surface-modified FA-CS@CuS NRs showed excellent antibacterial activity against Escherichia coli and Staphylococcus aureus. Hence, the proposed FA-CS@CuS NRs can be a suitable nanoagent for effective targeted anticancer and photothermal ablation treatment.

Near Infrared-Absorbing Nanoparticle-Mediated Endovascular Photothermal Precision Embolization of Tumor Feeding Vessels for Starvation Treatment.

Photothermal therapy has attracted enormous attention as an efficient treatment modality in cancer ablation but still encounters a major bottleneck due to the limited penetration depth of light inside tissues. To overcome the challenge of deep tissue penetration, we present a strategy of endovascular photothermal precision embolization (EPPE), which employs an endovascular optical fiber to induce local embolization only in the entrance of feeding vessels through photothermal heating for the purpose of fully blocking the blood supply of the whole tumor. In EPPE, we apply a highly efficient and biocompatible photothermal agent, i.e., near-infrared (NIR)-light-absorbing diketopyrrolopyrrole-dithiophene-based nanoparticle, which exhibits a high cell-killing efficacy at a concentration of 200 μg/mL using 808 nm laser irradiation of 0.5 W/cm2 within 5 min in both 2D cell culture and a 3D tumor spheroid model. We verify the feasibility of EPPE in an ex vivo organ-structured recellularized liver model and further confirm the in vivo efficacy of the photothermal treatment in a rat liver model. The photothermal treatment combined with the embolization effect holds promise to serve as an effective starvation therapy to treat tumors of varying sizes and locations.

Prostate Imaging after Focal Ablation (PI-FAB): A Proposal for a Scoring System for Multiparametric MRI of the Prostate After Focal Therapy

At present there is no standardised system for scoring the appearance of the prostate on multiparametric magnetic resonance imaging (MRI) after focal ablation for localised prostate cancer. We propose a novel scoring system, the Prostate Imaging after Focal Ablation (PI-FAB) score, to fill this gap. PI-FAB involves a 3-point scale for rating MRI sequences in sequential order: (1) dynamic contrast-enhanced sequences; (2) diffusion-weighted imaging, split into assessment of the high-b-value sequence first and then the apparent diffusion coefficient map; and (3) T2-weighted imaging. It is essential that the pretreatment scan is also available to help with this assessment. We designed PI-FAB using our experience of reading postablation scans over the past 15 years and include details for four representative patients initially treated with high-intensity focus ultrasound at our institution to demonstrate the scoring system. We propose PI-FAB as a standardised method for evaluating prostate MRI scans after treatment with focal ablation. The next step is to evaluate its performance across multiple experienced readers of MRI after focal therapy in a clinical data set. Patient summaryWe propose a scoring system called PI-FAB for assessing the appearance of magnetic resonance imaging scans of the prostate after focal treatment for localised prostate cancer. This will help clinicians in deciding on further follow-up.

Early enlarging cavitation after percutaneous microwave ablation of primary lung cancer

Purpose This retrospective study assessed the incidence rate, risk factors, and clinical course of early enlarging cavitation after percutaneous microwave ablation (MWA) of primary lung cancer (PLC). Methods This study included 557 lesions of 514 patients with PLC who underwent CT-guided percutaneous MWA between 1 January 2018 and 31 December 2021. Of these patients, 29 developed early enlarging cavitation and were enrolled in the cavity group, and 173 were randomly enrolled in the control group. Early enlarging cavitation of the lung was defined as the development of a cavity ≥30 mm within 7 days after MWA. Results Overall, 31 (5.57%, 31/557 tumors) early enlarging cavitations occurred at an average of 5.83 ± 1.55 d after MWA. The risk factors were lesion contact with a large vessel (diameter ≥3 mm), lesion contact with the bronchus (diameter ≥2 mm), and a large ablated parenchymal volume. The cavity group had a higher incidence rate of delayed hydropneumothorax (12.9%) and bronchopleural fistula (9.68%) than the control group, resulting in a longer hospitalization (9.09 ± 5.26 days). Until Dec 31, 2022, 27 cavities disappeared after a mean of 217.88 ± 78.57 d (range, 111–510 d), two persisted, and two were lost to follow-up. Conclusions Early enlarging cavitation occurred in 5.57% PLC cases that underwent MWA, causing serve complications and longer hospitalization. The risk factors were ablated lesion contact with large vessels and bronchi, as well as a larger ablated parenchymal volume.

In situ visualization of apoptosis process and modulation of cancer cell ablation based on a monocomponent multi-functional smart nanozyme

Nanozymes have exhibited an excellent prospect in cancer ablation. However, the real-time sensing of anticancer efficacy in catalytic process is often neglected. Designing the smart nanozymes for in situ visualizing treatment efficacy at subcellular level during catalytic therapy is crucial for precise cancer treatment, but hampered owing to the lack of a robust design strategy and efficient synthesis method. Herein, a monocomponent multi-functional photo-responsive carbon dots-based (CDs) nanozyme for instant self-predicting therapy efficacy and synchronous cancer cell ablation is developed through a direct microwave-assisted method. The CDs nanozyme can significantly induce cancer cell ablation due to its unique dual enzyme-mimic activities (oxidase-mimic and peroxidase-mimic), mitochondria-targeting ability, light-response feature improved synergistic therapy and high spatiotemporal selection. More importantly, the excessive reactive oxygen species (ROS) generated from catalytic treatment induces mitochondrial oxidative stress, accompanied by decreased mitochondrial membrane potential (MMP), which results in the transfer of CDs nanozyme from the mitochondrion to the nucleolus and thus enables the in situ real-time detection of therapy efficiency via fluorescent signal migration. This work not only represents an emerging paradigm with the self-predicting function for precise cancer treatment but also inspires the future design of the new generation of nanozyme.

Kidney cancer recurrence: predictors and outcomes of repeat partial nephrectomy (literature review)

In the last ten years, the number of organ preservation surgeries for kidney cancer significantly increased. Per literature data, the incidence of recurrences after partial nephrectomy is between 2.9 and 11 %, mostly they are located in the operated or contralateral kidney. Positive surgical margin, high stage and histological subtype of the tumor, as well as hereditary diseases, can serve as predictors for recurrences. In renal cancer recurrences, radical nephrectomy, ablation therapy and repeat tumor resection are possible treatment methods. Kidney resection, same as in primary renal tumors, leads to chronic kidney disease and cardiovascular complications. Different ablation methods, despite their low invasiveness, are not always technically possible. Therefore, in patients with kidney cancer recurrence and satisfactory functional status, repeat partial nephrectomy can be a method of choice. The literature describes the outcomes of open repeat kidney resection with high incidence of general and severe complications. The number of these complications significantly decreased due to the use of robot-assisted access for resection of recurrent renal tumors. Functional characteristics of repeat kidney resections do not significantly decrease, especially in robot-assisted partial nephrectomy. Oncological outcomes of these surgeries remain intermediate, further prospective multi-center trials are needed for their confirmation.

Mild photothermal/radiation therapy potentiates ferroptosis effect for ablation of breast cancer via MRI/PA imaging guided all-in-one strategy

BackgroundNanotheranostics advances anticancer management by providing therapeutic and diagnostic functions, that combine programmed cell death (PCD) initiation and imaging-guided treatment, thus increasing the efficacy of tumor ablation and efficiently fighting against cancer. However, mild photothermal/radiation therapy with imaging-guided precise mediating PCD in solid tumors, involving processes related to apoptosis and ferroptosis, enhanced the effect of breast cancer inhibition is not fully understood.ResultsHerein, targeted peptide conjugated gold nano cages, iRGD-PEG/AuNCs@FePt NPs ternary metallic nanoparticles (Au@FePt NPs) were designed to achieve photoacoustic imaging (PAI)/Magnetic resonance imaging (MRI) guided synergistic therapy. Tumor-targeting Au@FePt forms reactive oxygen species (ROS), initiated by X-ray-induced dynamic therapy (XDT) in collaboration with photothermal therapy (PTT), inducing ferroptosis-augmented apoptosis to realize effective antitumor therapeutics. The relatively high photothermal conversion ability of Au@FePt increases the temperature in the tumor region and hastens Fenton-like processes to achieve enhanced synergistic therapy. Especially, RNA sequencing found Au@FePt inducting the apoptosis pathway in the transcriptome profile.ConclusionAu@FePt combined XDT/PTT therapy activate apoptosis and ferroptosis related proteins in tumors to achieve breast cancer ablation in vitro and in vivo. PAI/MRI images demonstrated Au@FePt has real-time guidance for monitoring synergistic anti-cancer therapy effect. Therefore, we have provided a multifunctional nanotheranostics modality for tumor inhibition and cancer management with high efficacy and limited side effects.Graphical

Pilot ex vivo study on non-thermal ablation of human prostate adenocarcinoma tissue using boiling histotripsy

Focused ultrasound technologies are of growing interest for noninvasive ablation of localized prostate cancer (PCa). Here we present the results of the first case study evaluating the feasibility of non-thermal mechanical ablation of human prostate adenocarcinoma tissue using the boiling histotripsy (BH) method on ex vivo tissue. High intensity focused ultrasound field was generated using a 1.5-MHz custom-made transducer with nominal F#=0.75. A sonication protocol of 734 W acoustic power, 10-ms long BH-pulses, 30 pulses per focal spot, 1 % duty cycle, and 1 mm distance between single foci was tested in an ex vivo human prostate tissue sample containing PCa. The protocol used here has been successfully applied in the previous BH studies for mechanical disintegration of ex vivo prostatic human tissue with benign hyperplasia. BH treatment was monitored using B-mode ultrasound. Post-treatment histologic analysis demonstrated BH produced liquefaction of the targeted tissue volume. BH treated benign prostate parenchyma and PCa had similar tissue fractionation into subcellular fragments. The results of the study demonstrated that PCa tumor tissue can be mechanically ablated using the BH method. Further studies will aim on optimizing protocol parameters to accelerate treatment while maintaining complete destruction of the targeted tissue volume into subcellular debris.

Correction to: Local tumour residue after microwave ablation for lung cancer: a case report

Correction to: Local tumour residue after microwave ablation for lung cancer: a case report

Upgraded hydrodissection and its safety enhancement in microwave ablation of papillary thyroid cancer: a comparative study

Objectives To study the efficacy and safety of an improved hydrodissection protocol based on the perithyroidal fascial space during microwave ablation for papillary thyroid carcinoma (PTC). Methods The data of 341 patients (94 men and 247 women, median age 41 years old, 25%–75% interquartile range 34–53 years old, nodule maximum diameter 0.2–1.9 cm) who underwent microwave ablation for PTC were retrospectively reviewed. Among them, 185 patients underwent traditional hydrodissection and served as a control group, and 156 patients underwent improved hydrodissection based on perithyroidal fascial spaces, constituting the improved group. Improvements in safety were analyzed by comparing complications between the two groups. The characteristics of hydrodissected spaces, complications, and follow-up results were recorded. Results Hydrodissection was successfully performed in all enrolled patients according to the protocol. The incidence of hoarseness caused by recurrent laryngeal nerve injury, the most common complication in thermal ablation of thyroid nodules, was significantly lower in the improved group than in the control group (1.9% vs. 8.1%, p = 0.021). The median hoarseness recovery time in the improved group was shorter than that in the control group (2 months vs. 3 months, p = 0.032). During follow-up, no local recurrence was encountered in either group. The tumor disappearance rate was not significantly different between the two groups (69.9% vs. 75.7%, p = 0.228). Conclusions Improved hydrodissection based on perithyroidal fascial spaces had better protective effects than traditional hydrodissection.

Various Types of Facial-Angular Artery-Based Flaps for Reconstructing Oral and Maxillofacial Defects Following Cancer Ablation.

The flap based on the facial-angular vessels (FAVs) has several names and cannot capture the hemodynamics. This study was performed to assess the reliability of various types of flaps based on the FAVs for reconstructing oral and maxillofacial defects following cancer ablation. Forty-three oral and maxillofacial defects were reconstructed with facial-angular artery island flaps (FAAIF, n =14), including V-Y advancement-type and rotation-type flaps based on FAVs and reverse-flow FAAIFs (R-FAAIF, n =29), including ipsilateral, contralateral rotation, full-thickness, and folded types, based on distal FAVs following cancer ablation. The patients (25 males and 18 females) ranged in age from 18 to 82 years. The lesions included basal cell carcinoma ( n =26), squamous cell carcinoma ( n =8), adenoid cystic carcinoma ( n =3), mucoepidermoid carcinoma ( n =3), verrucous carcinoma ( n =2), and nodular melanoma ( n =1). The tumors were classified as clinical stage I to III in 12, 25, and 6 cases, respectively. Lesions were observed in orbital ( n =4), infraorbital ( n =14), glabellar ( n =2), nasal ( n =4), cheek ( n =10), upper lip ( n =3), palate ( n =4), and lower gingival ( n =2) regions. The defects ranged in size from 2.0×2.5 to 5.0×12.0cm. The skin paddle ranged in size from 1.5×3.0 to 4.0×12.0cm. There was 1 flap failure, resulting in a flap success rate of 97.7%. Complications, including hematoma, infection, wound dehiscence, and fistula, occurred in 15 (34.9%) patients. Limitations of mouth opening and ectropion occurred in 12 (28.0%) patients. The esthetic outcomes were satisfactory in 36 (83.7%) patients but were not significantly different between the FAAIF and R-FAAIF groups. The patients were followed up for 6 to 60 months. At the time of the last follow-up, 27 (62.8%) patients were alive with no disease, 9 (20.9%) were alive with disease, and 7 (16.3%) had died due to their disease. There was no significant survival difference between the 2 groups. Various types of FAV-based flaps are valuable reconstructive options for the treatment of oral and maxillofacial defects following clinical stage I-III cancer ablation.

A Computational Study Evaluating the Effects of Diffuser Length and Pullback Distance on the Ablation Zone During Laser Ablation Treatment of Liver Cancer

Abstract Although laser ablation is not commonly used for liver cancer treatment, there are several benefits that make it an appealing alternative. Nevertheless, investigations on the efficacy of laser ablation for liver cancer have been limited to few clinical trials. Therefore, not much is known regarding the efficacy of the technique especially when operating under different protocols and device parameters. In this study, we performed a numerical study to investigate the effects of diffuser length, power density, and the pullback technique on the coagulation zone formation during laser ablation of spherical liver cancer. The objective is to demarcate the influence of diffuser length from power density and to compare their performance to that when pullback is implemented. Four diffuser lengths (10, 15, 20, and 25 mm), and three pullback distances (5, 10, and 15 mm), were considered. Results showed that laser power density is a factor that limits the coagulation zone size when the diffuser length increases. A longer diffuser must be accompanied by an increase in laser power to achieve the desired treatment outcome. The pullback technique increases the effective diffuser length, but the coagulation volume obtained was smaller than that of a longer diffuser at the same power density. This suggests that increasing both the diffuser length and laser power is better at increasing the coagulation zone than the pullback technique. To obtain coagulation zone that is sufficiently large to cover the entire tumor, careful selection of the diffuser length, power density, and pullback distance is critical.

Design of Sonosensitizers Integrated with Resveratrol Motif for Synergetic Sonodynamic Therapy and Nuclear Factor Kappa B Transcription Suppression of Breast Cancer.

Sonodynamic therapy (SDT) has been recognized as a spatial-temporal and noninvasive modality for the treatment of deep-seated tumors. However, current sonosensitizers suffer from low sonodynamic efficacy. Herein, we reported the design of nuclear factor kappa B (NF-κB) targeting sonosensitizers (TR1, TR2, and TR3) by integrating a resveratrol motif into a conjugated electron donor-acceptor (triphenylamine benzothiazole) skeleton. Among these sonosensitizers, TR2 with two resveratrol units in one molecule was the most potent for inhibiting NF-κB signaling. Owing to the synergy of high sonodynamic efficacy and NF-κB activation inhibition, TR2 displayed a remarkable sonocytotoxicity to MCF-7 breast cancer cells. Xenograft mice studies demonstrated that TR2 had excellent anticancer potency and biosafety. This study thus opens up a new avenue for the development of efficient organic sonosensitizers for cancer ablation.

MR-Guided Transurethral Ultrasound Ablation of Prostate Cancer: Initial Experience of Monitoring Tumor Response by Dynamic Apparent Diffusion Coefficient Measurements at 3.0 T

Introduction: Diffusion-weighted imaging (DWI) as part of multiparametric magnetic resonance imaging (mpMRI) is an important sequence for the detection of prostate cancer (PCa). The objective of this retrospective analysis was to evaluate changes in apparent diffusion coefficient (ADC) measurements in biopsy-proven PCa undergoing TULSA-PRO (MR-guided transurethral ultrasound ablation of the prostate) at 3.0 T after 1, 3, and 6–12 months posttreatment. Methods: Nineteen patients underwent follow-up examinations after 1, 3, and 6–12 months including mpMRI at 3.0 T and urological-clinical examinations with quantitative analysis of ADCs. Results: In PCa, a significant increase of ADC values after 6–12 months was measured after TULSA-PRO treatment by 29.1% (pre-TULSA: 0.79 ± 0.16 × 10−3 mm2/s, 6–12 months: 1.02 ± 0.35 × 10−3 mm2/s), while the corresponding value in the reference tissue decreased by 48.5% (pre-TULSA: 1.20 ± 0.15 × 10−3 mm2/s, 6–12 months: 0.91 ± 0.29 × 10−3 mm2/s). The mean ADC values in the early follow-up groups at 1 and 3 months did not change significantly. Conclusion: DWI with ADC as part of mpMRI can serve as a biomarker to dynamically monitor the follow-up after TULSA after 6–12 months. For early posttreatment progression, it is not suitable due to too many confounding variables.

Cryo-assisted resection of primary breast cancer en bloc and tumor cryoablation connected with local drug delivery and targeting of tumor fluids. Experimental and clinical studies

Objective — to use cryosurgery in combination with simultaneous peritumoral and intratumoral tracer injections of blue dye for further lymphatic mapping in the treatment of primary breast tumors. The effectiveness of intraoperative cryoprobe‑assisted injection of blue dye and cytotoxic‑tracer mixture for locoregional drug targeting in the VX2 tumor model as well as its translational significance for cryo‑assisted breast tumor surgery with blue dye alone were evaluated. Sentinel lymph node mapping, pathological determination of the tumor, and resection margins were achievable.
 Materials and methods. Thirty‑nine patients with primary breast cancer in stages I to IV, aged 52,4 (±19) years (mean, standard deviation (SD) years), were randomly selected, treated at the Rudolfinerhaus Private Clinic in Vienna, Austria, and included in this preliminary clinical study. Under computed tomography guidance, we injected 2 ml of cytotoxic‑tracer mixture in five aliquots into the margins of 16 frozen or normothermic VX2 tumors. We evaluated the intraoperative and post‑operative drug targeting and therapeutic efficacy at the tumor‑host interface by means of computer tomography, gross examination, and histopathology. In thirty‑four T1 to T4 primary breast cancers, we performed an ultrasound‑guided cryoprobe‑assisted tumor freezing‑thawing cycle, blue dye‑guided lymphatic mapping, and surgery. We examined an intraoperative and freshly resected specimen and the blue dye distribution pattern in the tumor‑host interface, lymph node(s), breast parenchyma, and resection cavity. 
 Results. 29 of the 38 patients had localized primary breast cancer, which was estimated to be resectable without neoadjuvant chemotherapy. 87% of patients had one to twelve stained axillary lymph nodes, while 72% of patients had another quadrant and resection cavity stained. Fluid‑impervious frozen VX2 or breast tumors transported drug(s) in an arc‑like pattern at the tumor‑host interface regardless of freeze dose, number of freeze‑thaw cycles, drug dose fractionation, tumor characteristics, or tumor dimensions. During melting, the cytotoxic‑tracer mixture spread within 50% of the VX2 tumor and mirrored that of the tumor‑host interface; it was massive in normothermia. In VX2, the CT gap corresponded to 20% of the focal margin necrosis in pathology. In both studies, blue dye dose‑staining spread linearly in the tumor‑host interface and tumor.
 Conclusions. The study paves the way for intraoperative cryo‑assisted cure options for primary breast cancer. We have shown that our cryosurgical technique of repeatedly freezing deep tumors for en bloc resection or for in situ ablation of primary breast cancer, facilitated by IOUS monitoring, can be coupled with the simultaneous injection of dye tracers during conventional surgery, which then allows for lymphatic mapping. Intraoperative freezing‑assisted drug delivery and targeting techniques during cryoablation of the VX2 tumor translate successfully to locoregional blue dye targeting and lymphatic mapping during cryo‑assisted surgery of breast cancer. We explored the ability of our strategy to prevent tumor cell migration, but not that of injected tracers, to the lymphovascular drainage during conventional resection of frozen breast malignancies.