Complete Tumor Ablation Research Articles

Fluorescent Tissue Assessment of Colorectal Cancer Liver Metastases Ablation Zone: A Potential Real-Time Biomarker of Complete Tumor Ablation

This study aimed to evaluate whether rapid fluorescent tissue examination immediately after colorectal cancer liver metastasis (CLM) ablation correlates with standard pathologic and immunohistochemical (IHC) assessments. This prospective, National Institutes of Health-supported study enrolled 34 consecutive patients with 53 CLMs ablated between January 2011 and December 2014. Immediately after ablation, core needle sampling of the ablation zone was performed. Tissue samples were evaluated with fluorescent viability (MitoTracker Red) and nuclear (Hoechst) stains. Confocal microscope imaging was performed within 30min after ablation. The same samples were subsequently fixed and stained with hematoxylin and eosin (H&E). Identified tumor cells underwent IHC staining for proliferation (Ki67) and viability (OxPhos). The study pathologist, blinded to the H&E and IHC assessment, evaluated the fluorescent images separately to detect viable tumor cells. Sensitivity, specificity, and overall concordance of the fluorescent versus H&E and IHC assessments were calculated. A total of 63 tissue samples were collected and processed. The overall concordance rate between the immediate fluorescent and the subsequent H&E and IHC assessments was 94% (59/63). The fluorescent assessment sensitivity and specificity for the identification of tumor cells were respectively 100% (18/18) and 91% (41/45). The study showed a high concordance rate between the immediate fluorescent assessment and the standard H&E and IHC assessment of the ablation zone. Given the documented prognostic value of ablation zone tissue characteristics for outcomes after ablation of CLM, the fluorescent assessment offers a potential intra-procedural biomarker of complete tumor ablation.

04:12 PM Abstract No. 187 Efficacy and outcomes following percutaneous microwave ablation of hepatocellular carcinomas (HCC) measuring between 3 and 5 cm

Tumors greater than 3 cm have been considered less favorable for local percutaneous treatment, due to association with vascular invasion and higher histologic grade. The purpose of this study was to evaluate technical success and clinical outcomes of patients with HCC between 3-5 cm treated with CT-guided percutaneous microwave ablation (MWA). An institutional database was used to identify adult patients with HCC between 3-5 cm that were treated with CT-guided percutaneous MWA between August 2008 and December 2017. Patient demographics, tumor characteristics, and patient performance status were recorded. The diagnosis of HCC was established by biopsy or imaging criteria (OPTN). Primary efficacy rate was defined as the percentage of treated tumors that showed complete ablation of macroscopic tumor on the first follow-up scan. Secondary efficacy rate was defined as the percentage of residual tumors identified on post-procedure imaging (< 60 days) that were successfully re-treated. Once primary or secondary efficacy was achieved, patients were re-imaged at approximately 3-month intervals until they were censored due to loss of follow-up, death or transplantation. 367 patients underwent 544 MWA procedures over the study period. 61 patients (50 male, 11 female), had a diagnosis of HCC and lesion size of between 3 and 5 cm. Hydrodissection was performed in 27 cases. Mean follow-up was 822 days (range 27-3191). Of 61 lesions treated, no recurrence developed in the treated lesion in 41 cases. In the remaining 20 cases, recurrence developed, with mean time to recurrence of 335 days (range 24 – 1000 days). Recurrent tumor was managed with repeat ablation and/or intra-arterial therapy. Early recurrence (< 60 days) occurred in 3 cases, and was successfully treated with repeat ablation in two patients. 15 patients went on to subsequent liver transplantation, with analysis of the explants revealing no viable residual tumor in that area in 8 cases. There were 7 minor and no major complications. Advances in thermal ablation technology now allow for treatment of larger HCCs, with this study showing primary and secondary efficacy rates of 95.1% and 98.3%, respectively.

Photonic cancer nanomedicine using the near infrared-II biowindow enabled by biocompatible titanium nitride nanoplatforms.

Light-activated photoacoustic imaging (PAI) and photothermal therapy (PTT) using the second near-infrared biowindow (NIR-II, 1000-1350 nm) hold great promise for efficient tumor detection and diagnostic imaging-guided photonic nanomedicine. In this work, we report on the construction of titanium nitride (TiN) nanoparticles, with a high photothermal-conversion efficiency and desirable biocompatibility, as an alternative theranostic agent for NIR-II laser-excited photoacoustic (PA) imaging-guided photothermal tumor hyperthermia. Working within the NIR-II biowindow provides a larger maximum permissible exposure (MPE) and desirable penetration depth of the light, which then allows detection of the tumor to the full extent using PA imaging and complete tumor ablation using photothermal ablation, especially in deeper regions. After further surface polyvinyl-pyrrolidone (PVP) modification, the TiN-PVP photothermal nanoagents exhibited a high photothermal conversion efficiency of 22.8% in the NIR-II biowindow, and we further verified their high penetration depth using the NIR-II biowindow and their corresponding therapeutic effect on the viability of tumor cells in vitro. Furthermore, these TiN-PVP nanoparticles were developed as a contrast agent for NIR-II-activated PA imaging both in vitro and in vivo for the first time and realized efficient photothermal ablation of the tumor in vivo within both the NIR-I and NIR-II biowindows. This work not only provides a paradigm for TiN-PVP photothermal nanoagents working in the NIR-II biowindow both in vitro and in vivo, but also proves the feasibility of PAI and PTT cancer theranostics using NIR-II laser excitation.

Enhancement of mitochondrial ROS accumulation and radiotherapeutic efficacy using a Gd-doped titania nanosensitizer

Radiotherapy is an extensively used treatment modality in the clinic and can kill malignant cells by generating cytotoxic reactive oxygen species (ROS). Unfortunately, excessive dosages of radiation are typically required because only a small proportion of the radiative energy is adsorbed by the soft tissues of a tumor, which results in the nonselective killing of normal cells and severe systemic side effects. An efficient nanosensitizer that makes cancer cells more sensitive to radiotherapy under a relatively low radiation dose would be highly desirable.Methods: In this study, we developed a Gd-doped titania nanosensitizer that targets mitochondria to achieve efficient radiotherapy. Upon X-ray irradiation, the nanosensitizer triggers a “domino effect” of ROS accumulation in mitochondria. This overabundance of ROS leads to mitochondrial permeability transition and ultimately irreversible cell apoptosis. Confocal laser imaging, western blotting and flow cytometry analysis were used to explore the biological process of intrinsic apoptosis induced by the nanosensitizer. Clonogenic survival assay, cell migration and invasion experiments were employed to evaluate the radiosensitizing effect of the nanosensitizer in vitro. Finally, to evaluate the therapeutic outcome of the nanosensitizer in vivo, MCF-7 tumor model was used.Results: Confocal laser images and western blotting data demonstrated that the nanosensitizer in conjunction with X-ray irradiation could induce cell apoptosis in ROS-mediated apoptotic signal pathways. A clonogenic survival assay revealed that cells treated with the prepared nanosensitizer exhibited a lower number of viable cell colonies than that of the nontargeted group under X-ray irradiation. Notably, with only a single dose of radiotherapy, the mitochondria-targeted nanosensitizer elicited the complete ablation of tumors in a mouse model.Conclusion: The designed nanosensitizer in combination with X-ray radiation exposure could be used for radiotherapy against cancer in living cells and in vivo. Moreover, the nanosensitizer with mitochondria targeting played a pivotal role in triggering a “domino effect” of ROS and cell apoptosis. The current strategy could provide new opportunities in designing efficient radiosensitizers for future cancer therapy.

Carbon dot-sensitized MoS2 nanosheet heterojunctions as highly efficient NIR photothermal agents for complete tumor ablation at an ultralow laser exposure.

Currently, one of the major hurdles hindering the clinical applications of photothermal therapy (PTT) and photothermal-chemo combination therapy (PCT) is the lack of highly efficient, readily derived, and irradiation-safe photothermal agents in the biologically transparent window. Herein, we report the first design and rational construction of 0D/2D/0D sandwich heterojunctions for greatly enhanced PTT and PCT performances using 0D N-doped carbon dots and 2D MoS2 nanosheets as the assembly units. The well-matching heterojunctions enabled an additional enhancement in NIR absorbance owing to the carrier injection from carbon dots to MoS2 nanosheets, and achieved a much higher photothermal conversion efficiency (78.2%) than that of single NIR-CDs (37.6%) and MoS2 (38.3%) only. In virtue of the heterojunction-based PTT, complete tumor recession without recurrence or pulmonary metastasis was realized at an ultralow and safe laser exposure (0.2 W cm-2) below the skin tolerance irradiation threshold. Furthermore, by taking advantage of the strong X-ray attenuation and effective drug loading capacity of MoS2 nanosheets, the CT imaging-guided PCT was achieved at 0.1 W cm-2, without inducing noticeable toxic side effects. Our findings can substantiate the potential of a novel 0D/2D heterojunction for cancer theranostics.

Integration of Polymerization and Biomineralization as a Strategy to Facilely Synthesize Nanotheranostic Agents.

Integration of biological macromolecules with inorganic materials via biomineralization has demonstrated great potential for development of nanotheranostic agents. To produce multifunctionality, integration of multiple components in the biomineralized theranostic agents is required; however, how to efficiently and reproducibly implement this is challenging. In this report, a universal biomineralization strategy is developed by incorporation of oxidization polymerization into albumin-templated biomineralization for facile synthesis of nanotheranostic agents. A series of biomineralized polymers and manganese dioxide hybrid nanoparticles (PMHNs) can be synthesized via the polymerization of various monomers, including dopamine (DA), epigallocatechin (EGC), pyrrole (PY), and diaminopyridine (DP), along with the reduction of KMnO4 and formation of manganese dioxide nanoparticles in albumin templates. These biomineralized PMHNs demonstrate ultrahigh MRI (longitudinal relaxivity up to 38 mM-1 s-1) and ultrasonic (US) imaging contrasting capabilities and have excellent photothermal therapy efficacy with complete ablation of orthotopic tumors. Moreover, these biomineralized hybrid nanoparticles can be effectively excreted through the kidneys, avoiding potential systemic toxicity. Thus, integration of polymerization into biomineralization presents a strategy for the fabrication of hybrid nanomaterials, allowing the production of multifunctional and biocompatible nanotheranostic agents via a facile one-pot method.

A personalized and long-acting local therapeutic platform combining photothermal therapy and chemotherapy for the treatment of multidrug-resistant colon tumor.

BackgroundLocal photothermal therapy (PTT) provides an easily applicable, noninvasive adjunctive therapy for colorectal cancer (CRC), especially when multidrug resistance (MDR) occurs. However, using PTT alone does not result in complete tumor ablation in many cases, thus resulting in tumor recurrence and metastasis.Materials and methodsIn this study, we aim to develop a personalized local therapeutic platform combining PTT with long-acting chemotherapy for the treatment of MDR CRC. The platform consists of polyethylene glycol (PEG)-coated gold nanorods (PEG-GNRs) and D-alpha-tocopheryl PEG 1000 succinate (TPGS)-coated paclitaxel (PTX) nanocrystals (TPGS-PTX NC), followed by the incorporation into an in situ hydrogel (gel) system (GNRs-TPGS-PTX NC-gel) before injection. After administration, PEG-GNRs can exert quick and efficient local photothermal response under near-infrared laser irradiation to shrink tumor; TPGS-PTX NC then provides a long-acting chemotherapy due to the sustained release of PTX along with the P-glycoprotein inhibitor TPGS to reverse the drug resistance.ResultsThe cytotoxicity studies showed that the IC50 of GNRs-TPGS-PTX NC-gel with laser irradiation decreased to ~178-folds compared with PTX alone in drug-resistant SW620 AD300 cells. In the in vivo efficacy test, after laser irradiation, the GNRs-TPGS-PTX NC-gel showed similar tumor volume inhibition compared with GNRs-gel at the beginning. However, after 14 days, the tumor volume of the mice treated with GNRs-gel quickly increased, while that of the mice treated with GNRs-TPGS-PTX NC-gel remained controllable due to the long-term chemotherapeutic effect of TPGS-PTX NC. The mice treated with GNRs-TPGS-PTX NC-gel also showed no weight loss and obvious organ damages and lesions during the treatment, indicating a low systemic side effect profile and a good biocompatibility.ConclusionOverall, the nano-complex may serve as a promising local therapeutic patch against MDR CRC with one-time dosing to achieve a long-term tumor control. The doses of PEG-GNRs and TPGS-PTX NC can be easily adjusted before use according to patient-specific characteristics potentially making it a personalized therapeutic platform.

Ultrasmall All-In-One Nanodots Formed via Carbon Dot-Mediated and Albumin-Based Synthesis: Multimodal Imaging-Guided and Mild Laser-Enhanced Cancer Therapy.

Integration of multiple diagnostic/therapeutic modalities into a single system with ultrasmall size, excellent photothermal/photodynamic properties, high cellular uptake efficiency, nuclear delivery capacity, rapid renal clearance, and good biosafety is highly desirable for cancer theranostics, but still remains challenging. Here, a novel type of multifunctional nanodots (denoted as BCCGH) was synthesized by mixing bovine serum albumin, carbon dots, and metal ions (Cu2+ and Gd3+), followed by the conjugation with a photosensitizer (HPPH). The nanodots hold great promise for fluorescence/photoacoustic/magnetic resonance/photothermal imaging-guided synergistic photothermal/photodynamic therapy (PDT) because of their appealing properties such as high photothermal conversion efficiency (68.4%), high longitudinal relaxivity (11.84 mM-1 s-1, 7 T), and superior colloidal stability with negligible Gd3+ release. Benefiting from the massive cellular uptake, endoplasmic reticulum/mitochondrion-targeting ability, and mild near-infrared laser irradiation-promoted nuclear delivery of BCCGH, a high anticancer therapeutic efficiency is achieved in the subsequent in vitro PDT. Besides, as revealed by the in vivo/ex vivo results, the nanodots also exhibit excellent tumor accumulation, efficient renal clearance, complete tumor ablation, and exceptional biosafety. To summarize, this work develops a carbon dot-mediated and albumin-based synthetic approach for constructing ultrasmall and multifunctional nanodots, which may hold great potential for cancer theranostics and beyond.

Engineering Metal-Organic Frameworks for Photoacoustic Imaging-Guided Chemo-/Photothermal Combinational Tumor Therapy.

Imaging-guided therapy has considerable potential in tumor treatment. Different treatments have been integrated to realize combinational tumor therapy with improved therapeutic efficiency. Herein, the conventional metal-organic framework (MOF) MIL-100 is utilized to load curcumin with excellent encapsulation capacity. Polydopamine-modified hyaluronic acid (HA-PDA) is coated on the MIL-100 surface to construct engineering MOF nanoparticles (MCH NPs). The HA-PDA coating not only improves the dispersibility and stability of NPs but also introduces a tumor-targeting ability to this nanosystem. A two-stage augmented photothermal conversion capability is introduced to this nanosystem by encapsulating curcumin in MIL-100 pores and then coating HA-PDA on the surface, which confer the MCH NPs with strong photothermal conversional efficiency. After being intravenously injected into xenograft HeLa tumor-bearing mice, MCH NPs prefer to accumulate at the tumor site and achieve photoacoustic imaging-guided chemo-/photothermal combinational tumor therapy, generating nearly complete tumor ablation. Engineering MOFs is an efficient platform for imaging-guided combinational tumor therapy, as confirmed by in vitro and in vivo evaluations.

Dual Imaging-Guided Oxidative-Photothermal Combination Anticancer Therapeutics.

Heme oxygenase-1 (HO-1) is a stress-response protein with potent cytoprotective and antioxidant activity, and its expression in cancer cells is enhanced in response to chemotherapy and radiotherapy. HO-1 is known to serve as a shield to protect cancer cells from anticancer therapy and attenuate apoptotic signals. It can be therefore reasoned that inhibition of HO-1 reduces the antioxidant level, making cancer cells more sensitive to photothermal heating. In this work, we developed dual imaging-guided oxidative-photothermal combination nanotherapeutics (OPCN) consisting of amphiphilic polymers conjugated with zinc protoporphyrin as a HO-1 inhibitor and fluorescent IR820 as a photothermal agent. A combination of OPCN and near-infrared (NIR) laser irradiation markedly increased the temperature and exerted significant toxicity through induction of apoptosis. In a mouse model of xenografts, tumors were identified by the strong fluorescence and photoacoustic signals. OPCN combined with NIR laser irradiation resulted in effective and complete thermal ablation of tumors without discernable side effects and tumor recurrence. We believe that OPCN hold tremendous translational potential for dual imaging-guided oxidative-photothermal combination anticancer therapy.

MRI-guided treatment in the breast.

In the last decades, an increasing interest has developed towards non-invasive breast lesion treatments, which offer advantages such as the lack of surgery-related complications, better cosmetic outcomes, and less psychological distress. In addition, these treatments could be an option for patients with poor health who are not candidates for surgery. Non-surgical ablation can be performed under magnetic resonance (MR) or ultrasound (US) guidance. US is cheaper and easily available, while contrast-enhanced MR is more accurate, ensuring better safety and efficacy for the patient. Overall results of studies about MRI-guided tumor ablation reported complete ablation rates ranging between 20% and 100%. High-intensity focused ultrasound (HIFU or FUS) is the most studied ablative technique and it is already established as a valid technique for ablation of benign and malignant tumors in various organs. Ultrasound-guided FUS is very useful for young patients who refuse surgery or with multiple nodules; however, MR-guided FUS is more sensitive and allows a better evaluation of thermal accumulation within the ablated tissue or the adjacent structures. Most MR-guided FUS studies used a dedicated high-field MR scanner and complete tumor ablation was reported in 17-90% of cases. Other techniques using thermal tissue destruction are radiofrequency ablation (RFA) and laser interstitial thermal therapy (LITT). Only a few studies assessed the efficacy of these treatments, all were performed with open MR devices. RFA showed complete tumor ablation in 30-96% of patients, while LITT in 10-71%, but all the studies had a small number of patients. Cryoablation obtains tissue ablation by a rapid decrease of temperature, with a complete tumor removal reported in 18-52% of cases with MR guidance. No serious complications were reported with these techniques. Currently, breast conservative surgery replaced radical surgery when possible. Therefore, future research should focus on these treatments to shift towards an even less invasive approach to breast neoplasms. Level of Evidence: 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018;48:1479-1488.

Multienzyme‐Mimicking Nanocomposite for Tumor Phototheranostics and Normal Cell Protection

AbstractSelectively regulating the reactive oxygen species (ROS) level in cells by redox modulation with nanoparticles mimicking multiple enzymes holds great promise for protecting normal cells against ROS threats and surpassing the current limitations of ROS‐dependent cancer therapy. Herein, we develop a new indocyanine green (ICG)‐bovine serum albumin (BSA)‐cerium‐manganese oxide nanocomposites (IBCM NCs) via facile one‐step biomineralization to functionally mimic superoxide dismutase and catalase. IBCM NCs can synergistically regulate superoxide, hydrogen peroxide, oxygen and glutathione levels in cancer cells as well as provide contrast for magnetic resonance imaging. Consequently, cancer hypoxia can be relieved, and the phototherapy efficiency can be dramatically enhanced, leading to a complete ablation of tumor under NIR laser irradiation. On the other hand, IBCM NCs can consume the superoxide and hydrogen peroxide in the normal cells to protect them against ROS threats. Our results demonstrate IBCM NCs can effectively resist ROS threats in normal cells and kill cancer cells through breaking the intracellular redox balance.

Real time evaluation of tissue optical properties during thermal ablation of ex vivo liver tissues

Complete ablation of liver tumors is vital for minimizing the risk of local tumor recurrence. Accurately identifying the hallmarks of tissue necrosis during thermal ablative therapies may significantly increase the efficacy of ablation, while minimizing unnecessary damage to the surrounding normal tissues or critical structures. Light propagation in biological tissues is sensitive to the tissue microstructure and chromophore concentrations. In our previous studies, we found that the wavelength (λ) averaged liver tissue absorption coefficient (µa) and reduced scattering coefficient (µs′) change significantly upon heating which may be used for assessment of tissue damage during thermal ablation of solid tumors. Here, we seek to demonstrate the use of an integrated fiber-optic probe for continuous monitoring of the local tissue temperature (T), µa(λ) and µs′(λ) during thermal ablation of ex vivo porcine livers. The wavelength-averaged (435–630 nm) tissue absorption and scattering (µa and µs′ ) increased rapidly at 45 °C and plateaued at 67 °C. The mean µa and µs′ for liver tissue at 37 °C (n = 10) were 8.5 ± 3.7 and 2.8 ± 1.1 cm−1, respectively. The relative changes in µa and µs′ at 37, 55, and 65 °C were significantly different (p < .02) from each other. A relationship between the relative changes in µa and µs′ and the degree of tissue damage estimated using the temperature-based Arrhenius model for porcine liver tissues was established and studied.

Multifunctional Theranostic Nanoparticles Derived from Fruit-Extracted Anthocyanins with Dynamic Disassembly and Elimination Abilities.

Low toxic theranostic nanoparticles that can simultaneously achieve effective tumor accumulation and rapid renal clearance are highly desired for imaging contrast agents and photothermal therapy (PTT) in tumor diagnosis and therapy. Herein, we report a one-pot method for preparing multifunctional nanoparticles (FeAP-NPs) based on the coordination interaction of natural polyphenols (anthocyanins) extracted from fruits, FeIII ions, and poly(l-glutamic acid)- g-methoxy poly(ethylene glycol) copolymers. The FeAP-NPs possess the following favorable advantages: (1) The components of FeAP-NPs originate from natural products, an endogenous element, and poly(amino acid) derivatives, guaranteeing their safety for in vivo application. (2) FeAP-NPs exhibit excellent dual photoacoustic (PA)/magnetic resonance (MR) imaging capacity and high photothermal efficiency. (3) FeAP-NPs can overcome the intractable dilemma of the enhanced permeability and retention (EPR) effect and renal clearance for nanomedicine through the dynamic disassembling ability, which induces a switch of the elimination pathway. Complete tumor ablation is realized by PTT in MCF-7-bearing nude mice under the precise guide of PA and MR imaging. The detailed evaluation of the safety, biodistribution, and elimination behaviors of FeAP-NPs is conducted in vitro or in vivo. This work provides a promising comprehensive solution for nanomedicine clinical application.

Clinical outcome in elderly Chinese patients with primary hepatocellular carcinoma treated with percutaneous microwave coagulation therapy (PMCT)

Percutaneous microwave ablation therapy (PMCT) has been recommended for elderly hepatocellular carcinoma (HCC) patients who cannot tolerate surgery due to their age or presence of comorbidities. Few studies have investigated efficacy and treatment outcomes for PMCT treatment in these patients, especially in China, where patients are more often diagnosed and treated early in life. This study evaluated the safety and efficacy of ultrasound-guided PMCT in treatment-naive elderly HCC patients, and analyzed risk factors associated with poor treatment outcomes.The 65 HCC patients in this retrospective study were divided into 2 groups: <65 years old or ≥65 years old. Patients received PMCT every month until tumor was unobservable and were then followed for 1 month after ablation. The primary clinical endpoint was the rate of complete tumor ablation, and secondary endpoints were progression-free survival and overall survival.Patients ≥65 years old had significantly poorer performance status than younger patients, but similar rates of complete ablation. Multiple tumors and hypertension were associated with a significantly higher risk of death, while higher postoperative alanine aminotransferase levels were associated with a significantly lower risk of death. Patients with tumor sizes >5 to ≤ 10 cm were at a significantly higher risk for disease progression than patients with tumor sizes >1 to ≤ 3 cm. Complete ablation significantly lowered the risk of disease progression.PMCT is safe and effective for patients ≥65 years of age, achieving total ablation in more than 90% of patients. Age and comorbidities did not affect clinical outcome.

A Novel Top-Down Synthesis of Ultrathin 2D Boron Nanosheets for Multimodal Imaging-Guided Cancer Therapy.

Single atom nonmetal 2D nanomaterials have shown considerable potential in cancer nanomedicines, owing to their intriguing properties and biocompatibility. Herein, ultrathin boron nanosheets (B NSs) are prepared through a novel top-down approach by coupling thermal oxidation etching and liquid exfoliation technologies, with controlled nanoscale thickness. Based on the PEGylated B NSs, a new photonic drug delivery platform is developed, which exhibits multiple promising features for cancer therapy and imaging, including: i) efficient NIR-light-to-heat conversion with a high photothermal conversion efficiency of 42.5%, ii) high drug-loading capacity and triggered drug release by NIR light and moderate acidic pH, iii) strong accumulation at tumor sites, iv) multimodal imaging properties (photoacoustic, photothermal, and fluorescence imaging), and v) complete tumor ablation and excellent biocompatibility. As far as it is known, this is the first report on the top-down fabrication of ultrathin 2D B NSs by the combined thermal oxidation etching and liquid exfoliation, as well as their application as a multimodal imaging-guided drug delivery platform. The newly prepared B NSs are also expected to provide a robust and useful 2D nanoplatform for various biomedical applications.

Phase 2 Open-Label Trial Investigating Percutaneous Laser Ablation for Treatment of Early-Stage Breast Cancer: MRI, Pathology, and Outcome Correlations

BackgroundAn institutional review board-approved, multicenter clinical trial was designed to determine the efficacy and outcome of percutaneous laser ablation (PLA) in the treatment of invasive ductal breast carcinoma (IDC). Post-ablation magnetic resonance imaging (MRI) was compared with surgical pathology in evaluation of residual post-ablation IDC and ductal carcinoma in situ.MethodsPatients with a single focus of IDC 20 mm or smaller by pre-ablation MRI were treated with PLA. The patients underwent a 28-day post-ablation MRI, followed by surgical resection. Cell viability criteria were applied to pre- and post-ablation pathology specimens, which evaluated hematoxylin–eosin (H&E), cytokeratin (CK) 8/18, estrogen receptor, and Ki67 staining patterns.ResultsIn this study, 61 patients were reported as the intention-to-treat cohort for determination of PLA efficacy. Of these 61 patients, 51 (84%) had complete tumor ablation confirmed by pathology analysis. One subject’s MRI imaging was not performed per protocol, which left 60 subjects evaluable for MRI pathology correlation. Five patients (8.3%) had residual IDC shown by both MRI and pathology. Post-ablation discordance was noted between MRI and pathology, with four patients (6.7%) false-positive and four patients (6.7%) false-negative. The negative predictive value (NPV) of MRI for all the patients was 92.2% (95% confidence interval [CI], 71.9–91.9%). Of the 47 patients (97.9%) with tumors 15 mm or smaller, 46 were completely ablated, with an MRI NPV of 97.7% (95% CI, 86.2–99.9%).ConclusionsPercutaneous laser ablation is a potential alternative to surgery for treatment of early-stage IDC. Strong correlations exist between post-ablation MRI and pathologic alterations in CK8/18, ER, and Ki67 staining.

Abstract 3705: Targeted anticancer drug delivery to Ewing's sarcoma using human anti-CD99 targeted hybrid polymerization liposomal nanoparticles

Abstract Most anticancer therapies are unspecific and therefore inevitably lead to off-target toxicity. To overcome these shortcomings, targetable hybrid polymerization liposomal nanoparticles (HPLNs) have been invented. Multiple innovative and proprietary technologies have been developed to enable creation of this unique form of nanoparticle therapy, including the use of cross linked lipids to improve both stability and bioavailability, modified polyethylene glycol (PEG) for both ‘stealthiness' (to prevent immune response to the nanoparticle) and for covalent attachment of targeting molecules such as tumor specific antibodies or peptides. Our present study showed the superior efficacy of human anti-CD99 targeted HPLNs in the treatment of Ewing sarcoma. Human monoclonal anti-CD99 antibody-targeted HPLNs encapsulating irinotecan (CD99-HPLN/Ir) can efficiently reach implanted Ewing sarcoma tumors in xenograft mice and dramatically reduce and/or eliminate the tumor burden. Complete tumor ablation has been observed at doses as low as 1 mg irinotecan/kg, treated twice per week. In other cases, animals who failed untargeted (HPLN/Ir) treatment showed complete tumor ablation after ‘salvage' treatment with CD99-HPLN/Ir. Our CD99 targeted HPLN/irinotecan formulation, termed NV103 showed much better efficacy than the commercial untargeted liposomal irinotecan (Onivyde™) and doxorubicin (Doxil™). Toxic side effects, normally associated with systemic administration of free irinotecan, were minimized or undetectable. Our nanoparticles showed excellent bioavailability. Even the untargeted HPLN/Ir improve drug bioavailability six-fold in a comparison experiment with the drug in liposome form (Onivyde™), with no discernable systemic toxicity. Antibody targeting of the HPLN irinotecan formulation (NV103) improves the efficacy 12-fold, over the untargeted liposome form. In conclusion, this formulation may be effective for treatment of other CD99-expressing tumors like certain leukemias, lymphomas and glioma. Ultimately, after development of other tumor-specific targeting agents and varied encapsulated therapeutics, this technology can be usefully adapted for the treatment of other cancers as well. Citation Format: Hyunggyoo Kang, Jon Nagy, Timothy Triche. Targeted anticancer drug delivery to Ewing's sarcoma using human anti-CD99 targeted hybrid polymerization liposomal nanoparticles [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3705.

Cryoablation of renal cell carcinoma: six-year experience with 64 cases

Objective To summarize our clinical experience of cryoablation for renal cancer and to analyze the therapeutic indication, security, selection of cryoablation and outcomes. Methods Sixty-four patients suffered with T1a renal cell carcinoma were enrolled in this study from March 2012 to March 2018. Among them, 5 cases were senile patients(≥80 years), 5 cases complicated with other cancers, 3 cases complicated with renal insufficiency, 4 cases complicated with decompensated cirrhosis, 3 cases with bilateral renal cancer, 4 cases with solitary kidney cancer and 39 cases with some other complications. The preoperative serum creatinine level was(80.5±38.2)μmol/L. The patients underwent laparoscopic single-site (LESS) renal cryoablation, conventional laparoscopic renal cryoablation, or percutaneous image-guided cryoablation according to individual situation. Contrast-enhanced CT scan or MRI were used during the procedures and follow-up was performed. Results All operations were completed successfully and technical success was achieved as well in all cases. Blood transfusion was necessary for 2 cases because of hemorrhage.The mean diameter of the mass was (2.6±0.90)cm , the median volume of blood loss was 50ml(10-110 ml), and the mean operation time was(96.0±24.5)min. The median inpatient hospital stay was 3 d(1-6 d). In one case, digital subtraction angiography(DSA )embolization was performed due to hemorrhage after surgery. None of the other cases had intraoperative or postoperative complications. The serum creatinine level after surgery was not significantly decreased [postoperative (83.8±42.1) μmol/L, P=0.64]. The contrast-enhanced CT or MRI of the kidneys one week postoperatively showed uniform low density in all lesion areas, which represented complete ablation and regression of the tumor. All cases were followed up regularly. One case showed relapse at the 6th month follow-up and underwent cryoablation again. Another case, who was not regularly followed up, relapsed at 69th month after surgery. No relapse was observed in the other cases during the follow-up. Conclusions Renal cancer cryoablation is a safe, feasible and efficacious therapy for the patients who suffered from unresectable T1a renal cell carcinoma because of high surgical risk or multifocal lesions. Key words: Carcinoma, renal cell; Cryoablation; Laparoscopy; Imaging-guided

The Evolving Role of Ultrasound Guided Percutaneous Laser Ablation in Elderly Unresectable Breast Cancer Patients: A Feasibility Pilot Study.

Background and Objectives Breast-conserving surgery represents the standard of care for the treatment of small breast cancers. However, there is a population of patients who cannot undergo the standard surgical procedures due to several reasons such as age, performance status, or comorbidity. Our aim was to investigate the feasibility and safety of percutaneous US-guided laser ablation for unresectable unifocal breast cancer (BC). Methods Between December 2012 and March 2017, 12 consecutive patients underwent percutaneous US-guided laser ablation as radical treatment of primary inoperable unifocal BC. Results At median follow-up of 28.5 months (range 6-51), no residual disease or progression occurred; the overall success rate for complete tumor ablation was therefore 100%. No significant operative side effects were observed, with only 2 (13.3%) experiencing slight to mild pain during the procedure, and all patients complained of a mild dull aching pain in the first week after procedure. Conclusions Laser ablation promises to be a safe and feasible approach in those patients who are not eligible to the standard surgical approach. However, longer follow-up results and larger studies are strongly needed.