Local Tumor Ablation Research Articles

Targeting Tumor Acidosis and Regulatory T Cells Unmasks Anti-Metastatic Potential of Local Tumor Ablation in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an immunologically heterogenous disease that lacks clinically actionable targets and is more likely to progress to metastatic disease than other types of breast cancer. Tumor ablation has been used to increase response rates to checkpoint inhibitors, which remain low for TNBC patients. We hypothesized that tumor ablation could produce an anti-tumor response without using checkpoint inhibitors if immunosuppression (i.e., Tregs, tumor acidosis) was subdued. Tumors were primed with sodium bicarbonate (200 mM p.o.) to reduce tumor acidosis and low-dose cyclophosphamide (100–200 mg/kg i.p.) to deplete regulatory T cells, as has been shown independently in previous studies. A novel injectable ablative was then used to necrose the tumor, release tumor antigens, and initiate an immune event that could create an abscopal effect. This combination of bicarbonate, cyclophosphamide, and ablation, called “BiCyclA”, was tested in three syngeneic models of TNBC: E0771 (C57BL/6), 67NR (BALB/c), and 4T1-Luc (BALB/c). In E0771 and 67NR, BiCyclA therapy significantly reduced tumor growth and cured 5/7 and 6/10 mice 50 days after treatment respectively. In the metastatic 4T1-Luc tumors, for which surgery and checkpoint inhibitors fail, BiCyclA cured 5/10 mice of primary tumors and lung metastases. Notably, CD4+ and CD8+ T cells were found to be crucial for the anti-metastatic response, and cured mice were able to resist tumor rechallenge, suggesting production of immune memory. Reduction of tumor acidity and regulatory T cells with ablation is a simple yet effective therapy for local and systemic tumor control with broad applicability as it is not limited by expensive supplies.

Th1-Dominant CD4+ T Cells Orchestrate Endogenous Systematic Antitumor Immune Memory After Cryo-Thermal Therapy.

Recent studies suggest that highly activated, polyfunctional CD4+ T cells are incredibly effective in strengthening and sustaining overall host antitumor immunity, promoting tumor-specific CD4+ T-cell responses and effectively enhancing antitumor immunity by immunotherapy. Previously, we developed a novel cryo-thermal therapy for local tumor ablation and achieved long-term survival rates in several tumor models. It was discovered that cryo-thermal therapy remodeled the tumor microenvironment and induced an antigen-specific CD4+ T-cell response, which mediated stronger antitumor immunity in vivo. In this study, the phenotype of bulk T cells in spleen was analyzed by flow cytometry after cryo-thermal therapy and both CD4+ Th1 and CD8+ CTL were activated. In addition, by using T-cell depletion, isolation, and adoptive T-cell therapy, it was found that cryo-thermal therapy induced Th1-dominant CD4+ T cells that directly inhibited the growth of tumor cells, promoted the maturation of MDSCs via CD4+ T-cell-derived IFN-γ and enhanced the cytotoxic effector function of NK cells and CD8+ T cells, and promoted the maturation of APCs via cell-cell contact and CD4+ T-cell-derived IFN-γ. Considering the multiple roles of cryo-thermal-induced Th1-dominant CD4+ T cells in augmenting antitumor immune memory, we suggest that local cryo-thermal therapy is an attractive thermo-immunotherapy strategy to harness host antitumor immunity and has great potential for clinical application.

Percutaneous local tumor ablation vs. stereotactic body radiotherapy for early-stage non-small cell lung cancer: a systematic review and meta-analysis.

Background:Percutaneous local tumor ablation (LTA) and stereotactic body radiotherapy (SBRT) have been regarded as viable treatments for early-stage lung cancer patients. The purpose of this study was to compare the efficacy and safety of LTA with SBRT for early-stage non-small cell lung cancer (NSCLC).Methods:PubMed, Embase, Cochrane library, Ovid, Google scholar, CNKI, and CBMdisc were searched to identify potential eligible studies comparing the efficacy and safety of LTA with SBRT for early-stage NSCLC published between January 1, 1991, and May 31, 2021. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were applied to estimate the effect size for overall survival (OS), progression-free survival (PFS), locoregional progression (LP), and adverse events.Results:Five studies with 22,231 patients were enrolled, including 1443 patients in the LTA group and 20,788 patients in the SBRT group. The results showed that SBRT was not superior to LTA for OS (HR = 1.03, 95% CI: 0.87–1.22, P = 0.71). Similar results were observed for PFS (HR = 1.09, 95% CI: 0.71–1.67, P = 0.71) and LP (HR = 0.66, 95% CI: 0.25–1.77, P = 0.70). Subgroup analysis showed that the pooled HR for OS favored SBRT in patients with tumors sized >2 cm (HR = 1.32, 95% CI: 1.14–1.53, P = 0.0003), whereas there was no significant difference in patients with tumors sized ≤2 cm (HR = 0.93, 95% CI: 0.64–1.35, P = 0.70). Moreover, no significant differences were observed for the incidence of severe adverse events (≥grade 3) (OR = 1.95, 95% CI: 0.63–6.07, P = 0.25) between the LTA group and SBRT group.Conclusions:Compared with SBRT, LTA appears to have similar OS, PFS, and LP. However, for tumors >2 cm, SBRT is superior to LTA in OS. Prospective randomized controlled trials are required to determine such findings.INPLASY Registration Number:INPLASY202160099

Single-cell RNA sequencing reveals localized tumour ablation and intratumoural immunostimulant delivery potentiate T cell mediated tumour killing.

BackgroundMetastatic breast cancer poses great challenge in cancer treatment. N‐dihydrogalactochitosan (GC) is a novel immunoadjuvant that stimulates systemic immune responses when administered intratumourally following local tumour ablation. A combination of photothermal therapy (PTT) and GC, referred to as localized ablative immunotherapy (LAIT), extended animal survival and generates an activated B cell phenotype in MMTV‐PyMT mouse mammary tumour microenvironment (TME). However, how T cell populations respond to LAIT remains to be elucidated.MethodsUsing depletion antibodies, we studied the contributions of CD8+ and CD4+ T cells to the therapeutic effect of LAIT. Using single‐cell RNA‐sequencing (scRNAseq), we analysed tumour‐infiltrating T cell heterogeneity and dissected their transcriptomes upon treatments of PTT, GC, and LAIT (PTT+GC).ResultsLoss of CD8+ T cells after LAIT abrogated the therapeutic benefits of LAIT. Ten days after treatment, proportions of CD8+ and CD4+ T cells in untreated TME were 19.2% and 23.0%, respectively. Upon LAIT, both proportions were increased to 25.5% and 36.2%, respectively. In particular, LAIT increased the proportions of naïve and memory cells from a resting state to an activated state. LAIT consistently induced the expression of co‐stimulatory molecules, type I IFN responsive genes, and a series of antitumor cytokines, Ifng, Tnf, Il1, and Il17 in CD8+ and CD4+ T cells. LAIT also induced immune checkpoints Pdcd1, Ctla4, and Lag3 expression, consistent with T cell activation. Relevant to clinical translation, LAIT also upregulated genes in CD8+ and CD4+ T cells that positively correlated with extended survival of breast cancer patients.ConclusionsOverall, our results reveal that LAIT prompts immunological remodelling of T cells by inducing broad proinflammatory responses and inhibiting suppressive signalling to drive antitumour immunity.

Percutaneous Ablation of Metastatic Lymph Nodes: An Insight from the Comparison of Efficacy and Safety Between Cryoablation and Radiofrequency Ablation.

To retrospectively compare efficacy and safety of computed tomography (CT)-guided percutaneous ablation of metastatic lymph nodes (LN) between cryoablation (CA) and radiofrequency ablation (RFA). A bi-central institutional database research identified 28 patients (42 metastatic LNs) who underwent percutaneous CT-guided ablation. RFA group included 18 patients/26 tumors;CA group included 10 patients/16 tumors. Contrast-enhanced CT or MRI was used for post-ablation follow-up. Patient and tumor characteristics, technical and clinical success on a per tumor and a per patient basis and complication rates were recorded, evaluated and compared between the 2 groups. Both RFA and CA groups had the same median tumor size (2.00 vs. 2.20cm, p = 0.257), the same median follow-up time (20.50 vs. 20.00months, p = 0.923) and the same median lengthof hospitalstay(1.00 vs. 1.00days, p = 0.283). CA group had a higher median procedure time (110.50 vs. 52.00min, p = 0.001). On a per lesion basis, the overall complete response post-ablation was88.46% (23/26 lesions) in the RFA and 93.75% (15/16 lesions) in the CA group; no association was revealed between local tumor control and ablation technique (p = 0.709). No complications were recorded in both Groups. On a per patient basis, CA had a longer disease-free interval (24.00 vs. 14.50, p = 0.012) which, however, did not affect the overall survival between the two techniques (26.0 vs. 22.0, p = 0.099 for CA and RFA respectively). Our limited data suggest that CT-guided RFA and CA are equally effective on terms of efficacy and safety for the treatment of metastatic lymph nodes.

ELECTROCHEMOTHERAPY IN THE TREATMENT OF UNRESECTABLE PANCREATIC CANCER

Pancreatic cancer (PC) is a malignant tumor with a poor prognosis and an extremely low 5-year survival rate. No more than 10% of patients have local cancer of the pancreas; in the rest, at the time of the initial diagnosis, it is already a systemic disease. In most patients, relapse occurs within the first 6 months after resection and adjuvant therapy. 95% of patients with prostate cancer require palliative therapy.
 For 40 years, the results of treatment of metastatic prostate cancer have improved slightly. Gemcitabine monotherapy increased overall survival to 6 months; combinations of gemcitabine with nab-paclitaxel, liposomal irinotecan with 5-FU, or FOLFIRINOX triplet did not achieve 1-year survival.
 To date, the survival limit of patients has been reached, and the likelihood of a radical change in the treatment paradigm over the next five years is very small.
 The results of current clinical trials examining the effects of new drugs in prostate cancer can be expected in about 8-10 years, with an estimated success rate of about 3%.
 A new method of local tumor ablation, which combines intravenous administration of cytostatics (for example, cisplatin or bleomycin) with exposure of tumor cells to constant currents with extremely short and intense pulses (8 nano-pulses of 100 microseconds duration), is the method of electrochemotherapy (clinical therapy).
 Unlike radiofrequency, microwave or laser ablation, in which tissues are destroyed as a result of high temperatures with the formation of a zone of coagulation necrosis, the method of electroporation is not associated with thermal exposure, it is safer and can be used in various clinical situations, including in the treatment of cancer. pancreas.
 Dynamic Electro-Amplified Chemotherapy (D-EECT) is a safe, simple and effective clinical method for treating large tumor masses. This method opens up a new direction and creates good prospects in the treatment of inoperable, chemoresistant and radioresistant tumors.
 In some studies, the median time to progression (PFS) and overall survival (OS) from the moment of diagnosis in patients with unresectable prostate cancer was 22.8 and 30.7 months, respectively, which clearly exceeds the same indicators when using standard methods of anticancer chemotherapy.
 The method of electrochemotherapy using Scandinavian ChemoTech AB equipment has already been registered in Ukraine and will soon improve the treatment of patients with complex tumors of various localizations, including those with unresectable forms of pancreatic cancer.

Exploration of Novel Pathways Underlying Irreversible Electroporation Induced Anti-Tumor Immunity in Pancreatic Cancer.

Advancements in medical sciences and technologies have significantly improved the survival of many cancers; however, pancreatic cancer remains a deadly diagnosis. This malignancy is often diagnosed late in the disease when metastases have already occurred. Additionally, the location of the pancreas near vital organs limits surgical candidacy, the tumor’s immunosuppressive environment limits immunotherapy success, and it is highly resistant to radiation and chemotherapy. Hence, clinicians and patients alike need a treatment paradigm that reduces primary tumor burden, activates systemic anti-tumor immunity, and reverses the local immunosuppressive microenvironment to eventually clear distant metastases. Irreversible electroporation (IRE), a novel non-thermal tumor ablation technique, applies high‐voltage ultra-short pulses to permeabilize targeted cell membranes and induce cell death. Progression with IRE technology and an array of research studies have shown that beyond tumor debulking, IRE can induce anti-tumor immune responses possibly through tumor neo-antigen release. However, the success of IRE treatment (i.e. full ablation and tumor recurrence) is variable. We believe that IRE treatment induces IFNγ expression, which then modulates immune checkpoint molecules and thus leads to tumor recurrence. This indicates a co-therapeutic use of IRE and immune checkpoint inhibitors as a promising treatment for pancreatic cancer patients. Here, we review the well-defined and speculated pathways involved in the immunostimulatory effects of IRE treatment for pancreatic cancer, as well as the regulatory pathways that may negate these anti-tumor responses. By defining these underlying mechanisms, future studies may identify improvements to systemic immune system engagement following local tumor ablation with IRE and beyond.

A Novel Multi-Mode Thermal Therapy for Colorectal Cancer Liver Metastasis: A Pilot Study.

A novel multi-mode thermal therapy was developed for local tumor ablation and the systemic stimulation of anti-tumor immunity, consisting of a rapid liquid nitrogen freezing, and followed by the radiofrequency heating of target tumor tissue. This pilot study aimed to compare the therapeutic effects of the new therapy with conventional radiofrequency ablation (RFA) on patients with colorectal cancer liver metastasis (CRCLM). From August 2016 to September 2019, thirty-one patients with CRCLM received either multi-mode thermal therapy (n = 17) or RFA (n = 14). Triphasic contrast-enhanced magnetic resonance imaging (MRI), routine blood tests, and peripheral blood immune responses were evaluated before the treatment and in 1, 3, 6, and 12 months after. Local tumor response and progression-free survival (PFS) were assessed using the Kaplan-Meier method, and pre- and post-treatment immune cell counts were analyzed using Mann-Whitney U and Wilcoxon tests. A significantly longer PFS was observed in the multi-mode thermal therapy group in comparison to that of the conventional RFA group (median, 11.4 versus 3.4 months, p = 0.022). It was found that multi-mode therapy induced the functional maturation of dendritic cells, promoted CD4+ T cell-mediated antitumor responses, and decreased regulatory T cells, contributing to better therapeutic efficacy in CRCLM patients.

Percutaneous ablation or minimally invasive partial nephrectomy for cT1a renal masses? A propensity score‐matched analysis

ObjectiveLocal tumor ablation to treat small renal mass is increasing. The aim of the present study was to compare oncologic outcomes among patients with T1 renal mass treated with partial nephrectomy and local tumor ablation.MethodsTo reduce the inherent differences between patients undergoing laparoscopic or robot‐assisted partial nephrectomy (n = 405) and local tumor ablation (n = 137), we used a 1:1 propensity score‐matched analysis. Local tumor ablation consisted of radiofrequency ablation and cryoablation. Disease‐free survival, overall survival and other causes mortality‐free survival rates were estimated using the Kaplan–Meier method. Multivariable logistic regression and competing‐risk regression models were used to identify predictors of complications, recurrence and other causes mortality, respectively.ResultsPartial nephrectomy had higher disease‐free survival estimates, as compared with local tumor ablation (92.8% vs 80.4% at 5 years, P = 0.02), with no significant difference between radiofrequency ablation and cryoablation (P = 0.9). Ablation showed comparable overall survival estimates to partial nephrectomy (91% vs 95.8% at 5 years, P = 0.6). The 5‐year recurrence rates were 7.9% versus 23.8% for patients aged ≤70 years, and 2.5% versus 11.9% for patients aged >70 years treated with partial nephrectomy and ablation, respectively; the 5‐year other causes mortality rates were 0% and 2.2% for patients treated with partial nephrectomy and ablation aged ≤70 years, and 3% versus 10.9% for patients aged >70 years treated with partial nephrectomy and ablation, respectively. At multivariable analysis, ablation was associated with fewer complications (odds ratio 0.41; P = 0.01). At competing risks analysis, age (hazard ratio 0.96) and ablation (hazard ratio 4.56) were independent predictors of disease recurrence (all P ≤ 0.008).ConclusionsLocal tumor ablation showed a higher risk of recurrence and lower risk of complications compared with partial nephrectomy, with comparable overall survival rates.

PD16-05 PERC-SCORE: A NEPHROMETRY SCORE FOR PERCUTANEOUS TUMOR ABLATION OF SMALL RENAL MASS

You have accessJournal of UrologyKidney Cancer: Localized: Surgical Therapy II (PD16)1 Sep 2021PD16-05 PERC-SCORE: A NEPHROMETRY SCORE FOR PERCUTANEOUS TUMOR ABLATION OF SMALL RENAL MASS Lorenzo Bianchi, Pietro Piazza, Francesco Chessa, Angelo Mottaran, Carlo Casablanca, Matteo Droghetti, Carlo Roveroni, Francesco Costa, Marco Salvador, Stefano Puliatti, Caterina Gaudiano, Alberta Cappelli, Alessandro Bertaccini, Emanuela Marcelli, Angelo Porreca, Bernardino De Concilio, Rita Golfieri, Carla Serra, Antonio Celia, Riccardo Schiavina, and Eugenio Brunocilla Lorenzo BianchiLorenzo Bianchi More articles by this author , Pietro PiazzaPietro Piazza More articles by this author , Francesco ChessaFrancesco Chessa More articles by this author , Angelo MottaranAngelo Mottaran More articles by this author , Carlo CasablancaCarlo Casablanca More articles by this author , Matteo DroghettiMatteo Droghetti More articles by this author , Carlo RoveroniCarlo Roveroni More articles by this author , Francesco CostaFrancesco Costa More articles by this author , Marco SalvadorMarco Salvador More articles by this author , Stefano PuliattiStefano Puliatti More articles by this author , Caterina GaudianoCaterina Gaudiano More articles by this author , Alberta CappelliAlberta Cappelli More articles by this author , Alessandro BertacciniAlessandro Bertaccini More articles by this author , Emanuela MarcelliEmanuela Marcelli More articles by this author , Angelo PorrecaAngelo Porreca More articles by this author , Bernardino De ConcilioBernardino De Concilio More articles by this author , Rita GolfieriRita Golfieri More articles by this author , Carla SerraCarla Serra More articles by this author , Antonio CeliaAntonio Celia More articles by this author , Riccardo SchiavinaRiccardo Schiavina More articles by this author , and Eugenio BrunocillaEugenio Brunocilla More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001998.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Many nephrometry scores have been developed to quantify the complexity of renal tumours and to predict complications after partial nephrectomy. However, no specific nephrometry score have been developed for percutaneous local tumour ablation (LTA). To propose a novel nephrometry score (PERC-score) to predict the risk of postoperative complications in patients treated with LTA. METHODS: We retrospectively evaluated 160 patients with T1a renal mass treated with LTA at two tertiary centers (80 radiofrequency ablation [RFA], 80 cryoablation [Cryo]). To propose a score targeted for LTA, the following parameters were recorded, and a score was assigned to each item based on results of univariate logistic regressions: tumor’s size <2 cm (1), 2-3 cm (2) and 3.1-4 cm (3); renal hilum not involved (1) and renal hilum involved (2); no dislocation of urinary collecting system (UCS, 1) and dislocation/infiltration of UCS (2); technique of ablation, Cryo (1) and RFA (2). Total score was categorized in low (4-6) and high (7-9) risk, according to risk of complications. LOESS plot was produced using mean value of PERC-score to estimate the rate of complications predicted by the model. ROC curves were used to test the accuracy of different scoring systems (PERC, RENAL, PADUA and SPARE) in predicting overall complications. RESULTS: Overall, 23 (14.3%) postoperative complications were recorded. Median follow up was 34 months. Overall complications were significantly higher in patients with larger tumor size (>3 cm), renal hilum involvement, UCS dislocation/infiltration and higher PERC-score (all p≤0.04). At linear regression analysis, PERC-score revealed statistically significant correlation with postoperative complications (OR 3.6, CI 1.3-4.8, p<0.001). PERC-score showed higher accuracy to predict overall complications compared to PADUA, RENAL and SPARE score with AUC of 0.71 (CI 0.6-0.8, p=0.003) vs 0.65 (CI 0.5-0.8, p=0.01) vs 0.65 (CI 0.5-0.7, p=0.01) vs 0.65 (CI 0.5-0.7, p=0.02), respectively. CONCLUSIONS: PERC-score is easy to assess, basing on anatomic characteristic of renal mass from conventional imaging and more accurate than other nephrometry scores develop for partial nephrectomy to predict postoperative complications in patients treated with percutaneous ablation for T1a renal tumor. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e279-e280 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lorenzo Bianchi More articles by this author Pietro Piazza More articles by this author Francesco Chessa More articles by this author Angelo Mottaran More articles by this author Carlo Casablanca More articles by this author Matteo Droghetti More articles by this author Carlo Roveroni More articles by this author Francesco Costa More articles by this author Marco Salvador More articles by this author Stefano Puliatti More articles by this author Caterina Gaudiano More articles by this author Alberta Cappelli More articles by this author Alessandro Bertaccini More articles by this author Emanuela Marcelli More articles by this author Angelo Porreca More articles by this author Bernardino De Concilio More articles by this author Rita Golfieri More articles by this author Carla Serra More articles by this author Antonio Celia More articles by this author Riccardo Schiavina More articles by this author Eugenio Brunocilla More articles by this author Expand All Advertisement Loading ...

Salvage Robot-assisted Renal Surgery for Local Recurrence After Surgical Resection or Renal Mass Ablation: Classification, Techniques, and Clinical Outcomes

BackgroundSalvage treatment for local recurrence after prior partial nephrectomy (PN) or local tumor ablation (LTA) for kidney cancer is, as of yet, poorly investigated. ObjectiveTo classify the treatments and standardize the nomenclature of salvage robot-assisted renal surgery, to describe the surgical technique for each scenario, and to investigate complications, renal function, and oncologic outcomes. Design, setting, and participantsSixty-seven patients underwent salvage robot-assisted renal surgery from October 2010 to December 2020 at nine tertiary referral centers. Surgical procedureSalvage robot-assisted renal surgery classified according to treatment type as salvage robot-assisted partial or radical nephrectomy (sRAPN or sRARN) and according to previous primary treatment (PN or LTA). MeasurementsPostoperative complications, renal function, and oncologic outcomes were assessed. Results and limitationsA total of 32 and 35 patients underwent salvage robotic surgery following PN and LTA, respectively. After prior PN, two patients underwent sRAPN, while ten underwent sRARN for a metachronous recurrence in the same kidney. No intra- or perioperative complication occurred. For local recurrence in the resection bed, six patients underwent sRAPN, while 14 underwent sRARN. For sRAPN, the intraoperative complication rate was 33%; there was no postoperative complication. For sRARN, there was no intraoperative complication and the postoperative complication rate was 7%. At 3 yr, the local recurrence-free rates were 64% and 82% for sRAPN and sRARN, respectively, while the 3-yr metastasis-free rates were 80% and 79%, respectively. At 33 mo, the median estimated glomerular filtration rates (eGFRs) were 57 and 45 ml/min/1.73 m2 for sRAPN and sRARN, respectively. After prior LTA, 35 patients underwent sRAPN and no patient underwent sRARN. There was no intraoperative complication; the overall postoperative complications rate was 20%. No local recurrence occurred. The 3-yr metastasis-free rate was 90%. At 43 mo, the median eGFR was 38 ml/min/1.73 m2. The main limitations are the relatively small population and the noncomparative design of the study. ConclusionsSalvage robot-assisted surgery has a safe complication profile in the hands of experienced surgeons at high-volume institutions, but the risk of local recurrence in this setting is non-negligible. Patient summaryPatients with local recurrence after partial nephrectomy or local tumor ablation should be aware that further treatment with robot-assisted surgery is not associated with a worrisome complication profile, but also that they are at risk of further recurrence.

Radiofrequency ablation and chemotherapy versus chemotherapy alone for locally advanced pancreatic cancer (PELICAN): study protocol for a randomized controlled trial

BackgroundApproximately 80% of patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy, of whom approximately 10% undergo a resection. Cohort studies investigating local tumor ablation with radiofrequency ablation (RFA) have reported a promising overall survival of 26–34 months when given in a multimodal setting. However, randomized controlled trials (RCTs) investigating the effect of RFA in combination with chemotherapy in patients with LAPC are lacking.MethodsThe “Pancreatic Locally Advanced Unresectable Cancer Ablation” (PELICAN) trial is an international multicenter superiority RCT, initiated by the Dutch Pancreatic Cancer Group (DPCG). All patients with LAPC according to DPCG criteria, who start with FOLFIRINOX or (nab-paclitaxel/)gemcitabine, are screened for eligibility. Restaging is performed after completion of four cycles of FOLFIRINOX or two cycles of (nab-paclitaxel/)gemcitabine (i.e., 2 months of treatment), and the results are assessed within a nationwide online expert panel. Eligible patients with RECIST stable disease or objective response, in whom resection is not feasible, are randomized to RFA followed by chemotherapy or chemotherapy alone. In total, 228 patients will be included in 16 centers in The Netherlands and four other European centers. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, RECIST response, CA 19.9 and CEA response, toxicity, quality of life, pain, costs, and immunomodulatory effects of RFA.DiscussionThe PELICAN RCT aims to assess whether the combination of chemotherapy and RFA improves the overall survival when compared to chemotherapy alone, in patients with LAPC with no progression of disease following 2 months of systemic treatment.Trial registrationDutch Trial RegistryNL4997. Registered on December 29, 2015. ClinicalTrials.govNCT03690323. Retrospectively registered on October 1, 2018

Immune Modulation Plus Tumor Ablation: Adjuvants and Antibodies to Prime and Boost Anti-Tumor Immunity In Situ.

In situ tumor ablation techniques, like radiotherapy, cryo- and heat-based thermal ablation are successfully applied in oncology for local destruction of tumor masses. Although diverse in technology and mechanism of inducing cell death, ablative techniques share one key feature: they generate tumor debris which remains in situ. This tumor debris functions as an unbiased source of tumor antigens available to the immune system and has led to the concept of in situ cancer vaccination. Most studies, however, report generally modest tumor-directed immune responses following local tumor ablation as stand-alone treatment. Tumors have evolved mechanisms to create an immunosuppressive tumor microenvironment (TME), parts of which may admix with the antigen depot. Provision of immune stimuli, as well as approaches that counteract the immunosuppressive TME, have shown to be key to boost ablation-induced anti-tumor immunity. Recent advances in protein engineering have yielded novel multifunctional antibody formats. These multifunctional antibodies can provide a combination of distinct effector functions or allow for delivery of immunomodulators specifically to the relevant locations, thereby mitigating potential toxic side effects. This review provides an update on immune activation strategies that have been tested to act in concert with tumor debris to achieve in situ cancer vaccination. We further provide a rationale for multifunctional antibody formats to be applied together with in situ ablation to boost anti-tumor immunity for local and systemic tumor control.

A Heterojunction Structured WO2.9-WSe2 Nanoradiosensitizer Increases Local Tumor Ablation and Checkpoint Blockade Immunotherapy upon Low Radiation Dose.

Radiotherapy (RT) in practical use often suffers from off-target side effects and ineffectiveness against hypoxic tumor microenvironment (TME) as well as remote metastases. With regard to these problems, herein, we provide semiconductor heterojunction structured WO2.9-WSe2-PEG nanoparticles to realize a synergistic RT/photothermal therapy (PTT)/checkpoint blockade immunotherapy (CBT) for enhanced antitumor and antimetastatic effect. Based on the heterojunction structured nanoparticle with high Z element, the nanosystem could realize non-oxygen-dependent reactive oxygen species generation by catalyzing highly expressed H2O2 in TME upon X-ray irradiation, which could further induce immunogenic cell death. Meanwhile, this nanosystem could also induce hyperthermia upon near-infrared irradiation to enhance RT outcome. With the addition of anti-PD-L1 antibody-based CBT, our results give potent evidence that local RT/PTT upon mild temperature and low radiation dose could efficiently ablate local tumors and inhibit tumor metastasis as well as prevent tumor rechallenge. Our study provides not only one kind of radiosensitizer based on semiconductor nanoparticles but also a versatile nanoplatform for simultaneous triple-combined therapy (RT/PTT/CBT) for treating both local and metastasis tumors.

PD08-10 LOCAL ABLATION OF RENAL TUMORS: REAL COMPETITOR OF PARTIAL NEPHRECTOMY? A PROPENSITY-SCORE MATCHING ANALYSIS

You have accessJournal of UrologyKidney Cancer: Localized: Ablative Therapy (PD08)1 Apr 2020PD08-10 LOCAL ABLATION OF RENAL TUMORS: REAL COMPETITOR OF PARTIAL NEPHRECTOMY? A PROPENSITY-SCORE MATCHING ANALYSIS Lorenzo Bianchi, Pietro Piazza*, Riccardo Schiavina, Francesco Chessa, Amelio Ercolino, Matteo Droghetti, Alessandro Colella, Angelo Mottaran, Martina Masetti, Carla Serra, Caterina Gaudiano, Bernardino De Concilio, Antonio Celia, and Eugenio Brunocilla Lorenzo BianchiLorenzo Bianchi More articles by this author , Pietro Piazza*Pietro Piazza* More articles by this author , Riccardo SchiavinaRiccardo Schiavina More articles by this author , Francesco ChessaFrancesco Chessa More articles by this author , Amelio ErcolinoAmelio Ercolino More articles by this author , Matteo DroghettiMatteo Droghetti More articles by this author , Alessandro ColellaAlessandro Colella More articles by this author , Angelo MottaranAngelo Mottaran More articles by this author , Martina MasettiMartina Masetti More articles by this author , Carla SerraCarla Serra More articles by this author , Caterina GaudianoCaterina Gaudiano More articles by this author , Bernardino De ConcilioBernardino De Concilio More articles by this author , Antonio CeliaAntonio Celia More articles by this author , and Eugenio BrunocillaEugenio Brunocilla More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000835.010AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Due to the low morbidity, local tumor ablation (LTA) like Cryoablation (Cryo) and Radiofrequency ablation (RFA), are gaining popularity as alternative to PN. The aim of our study is to compare oncologic outcomes in patients treated with PN and LTA in a matched cohort of patients with T1 renal mass. METHODS: We identified a retrospective population of patients underwent LTA (percutaneous Cryo or RFA n=146) or PN (open, laparoscopic or robotic; n=594) in two tertiary centers. A propensity score 1:1 match (adjusting for age, Charlson Comorbidity Index [CCI], clinical size of tumor, PADUA score and preop eGFR) analysis was performed between the two groups (LTA n=146 and PN n=146). Clinicopathologic, perioperative and oncologic outcomes were compared. Finally, cumulative-incidence plots were generated for cancer specific mortality (CSM) and other causes mortality (OCM) according to the competing-risks method, after stratifying patients by treatments (LTA vs PN) and age (≤70 yrs vs >70 yrs). RESULTS: No significant differences were found between the two groups concerning preoperative patients’ and tumor’s characteristics. Post-operative complications rate was higher in the PN group compared to LTA group (26% vs 11% p=0.001). The median hospital stay was lower in the LTA group compared to PN group (2 vs 5 days p<0.001). The 8-yrs disease free survival (DFS) rates were 72% and 89% in LTA group and PN group (p=0,001). After stratifying according to technique (RFA vs Cryo vs PN), the 8-yrs DFS rates were 67% vs 76% vs 89% (RFA vs PN p<0.001; RFA vs Cryo p=0.3; Cryo vs PN p=0.1). At multivariate analysis CCI (Hazard ratio [HR] 1.58), number of synchronous tumors (HR 5.18) and LTA (HR 5.33) were independent predictors of disease recurrence (all p≤0.002). The 10-yr CSM rates were 6.7% vs 6.2% for patients aged ≤70 years and 2.2% vs 6.5% for patients aged >70 years treated with PN and PCA. The 10-yr OCM rates was 0% and 2.7% for patients treated with PN and ablative techniques aged ≤70 years and 9.1% vs 39% for patients aged >70 year treated with PN and ablative techniques, respectively. CONCLUSIONS: LTA are affected by higher rates of cancer recurrence compared to PN. However, due to reduced risk of complications, PCA are attractive alternative to PN in patients unfit for surgery or when the preservation of renal function is essential. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e172-e172 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lorenzo Bianchi More articles by this author Pietro Piazza* More articles by this author Riccardo Schiavina More articles by this author Francesco Chessa More articles by this author Amelio Ercolino More articles by this author Matteo Droghetti More articles by this author Alessandro Colella More articles by this author Angelo Mottaran More articles by this author Martina Masetti More articles by this author Carla Serra More articles by this author Caterina Gaudiano More articles by this author Bernardino De Concilio More articles by this author Antonio Celia More articles by this author Eugenio Brunocilla More articles by this author Expand All Advertisement PDF downloadLoading ...

MP21-04 THE EFFECT OF AGE ON CANCER-SPECIFIC MORTALITY IN T1A STAGE RENAL CELL CARCINOMA PATIENTS ACROSS ALL TREATMENT’S MODALITIES: A SEER-BASED STUDY

You have accessJournal of UrologyKidney Cancer: Localized: Surgical Therapy III (MP21)1 Apr 2020MP21-04 THE EFFECT OF AGE ON CANCER-SPECIFIC MORTALITY IN T1A STAGE RENAL CELL CARCINOMA PATIENTS ACROSS ALL TREATMENT’S MODALITIES: A SEER-BASED STUDY Angela Pecoraro*, Sophie Knipper, Carlotta Palumbo, Brescia Italy, Giuseppe Rosiello, Stefano Luzzago, Marina Deuker, Franciska Stolzenbach, Zhe Tian, Shahrokh F. Shariat, Fred Saad, Alberto Briganti, Cristian Fiori, Francesco Porpiglia, and Pierre I. Karakiewicz Angela Pecoraro*Angela Pecoraro* More articles by this author , Sophie KnipperSophie Knipper More articles by this author , Carlotta PalumboCarlotta Palumbo More articles by this author , Brescia ItalyBrescia Italy More articles by this author , Giuseppe RosielloGiuseppe Rosiello More articles by this author , Stefano LuzzagoStefano Luzzago More articles by this author , Marina DeukerMarina Deuker More articles by this author , Franciska StolzenbachFranciska Stolzenbach More articles by this author , Zhe TianZhe Tian More articles by this author , Shahrokh F. ShariatShahrokh F. Shariat More articles by this author , Fred SaadFred Saad More articles by this author , Alberto BrigantiAlberto Briganti More articles by this author , Cristian FioriCristian Fiori More articles by this author , Francesco PorpigliaFrancesco Porpiglia More articles by this author , and Pierre I. KarakiewiczPierre I. Karakiewicz More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000854.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The effect of age on cancer-specific mortality (CSM) is always tested in specific subgroup of patient with T1a non metastatic renal cell carcinoma (nmRCC). We tested the effect of age on CSM across all treatment modalities. METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2016), we identified 44,147 T1a nmRCC patients. Cumulative incidence plots and multivariable competing-risks regression analyses (MCR) model CSM. Separate models were fitted for each of four examined treatment modalities: partial nephrectomy [PN], radical nephrectomy [RN], local tumour ablation [LTA] and non-interventional management [NIM]. RESULTS: Patient distribution was as follows: 19602 (44.4%) <60 years; 13541 (30.7%) 60-69 years; 8637 (19.6%) 70-79 years and 2367 (5.4%) ≥ 80 years. Overall, 5- and 10-year CSM rates increased with increasing of age, across all four examined treatment modalities. In MCR focusing on PN, RN and LTA, older age independently predicted CSM in a dose-response fashion where the magnitude of CSM increased with increasing age. Conversely, in MCR for NIM the dose-response effect evidenced by a gradual increase in CSM across age categories was not recorded. In MCR models focusing on NIM patients CSM was only higher in the oldest age category, relative to three younger age categories. CONCLUSIONS: We are the first examining the effect of older age in T1a RCC across all treatment modalities, which minimize the effect of selection biases. This comprehensive analysis corroborated that more advanced age is invariably associated with increasingly higher CSM in patients treated with LTA, PN and RN. Conversely, in NIM patients the association with more advanced age with CSM was only evidenced in the highest age. In consequence, older T1a RCC patients appear to harbor more aggressive RCC phenotype than their younger counterparts. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e318-e319 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Angela Pecoraro* More articles by this author Sophie Knipper More articles by this author Carlotta Palumbo More articles by this author Brescia Italy More articles by this author Giuseppe Rosiello More articles by this author Stefano Luzzago More articles by this author Marina Deuker More articles by this author Franciska Stolzenbach More articles by this author Zhe Tian More articles by this author Shahrokh F. Shariat More articles by this author Fred Saad More articles by this author Alberto Briganti More articles by this author Cristian Fiori More articles by this author Francesco Porpiglia More articles by this author Pierre I. Karakiewicz More articles by this author Expand All Advertisement PDF downloadLoading ...

In vivo ultrasound thermal ablation control using echo decorrelation imaging in rabbit liver and VX2 tumor.

The utility of echo decorrelation imaging feedback for real-time control of in vivo ultrasound thermal ablation was assessed in rabbit liver with VX2 tumor. High-intensity focused ultrasound (HIFU) and unfocused (bulk) ablation were performed using 5 MHz linear image-ablate arrays. Treatments comprised up to nine lower-power sonications, followed by up to nine higher-power sonications, ceasing when the average cumulative echo decorrelation within a control region of interest exceeded a predefined threshold (− 2.3, log10-scaled echo decorrelation per millisecond, corresponding to 90% specificity for tumor ablation prediction in previous in vivo experiments). This threshold was exceeded in all cases for both HIFU (N = 12) and bulk (N = 8) ablation. Controlled HIFU trials achieved a significantly higher average ablation rate compared to comparable ablation trials without image-based control, reported previously. Both controlled HIFU and bulk ablation trials required significantly less treatment time than these previous uncontrolled trials. Prediction of local liver and VX2 tumor ablation using echo decorrelation was tested using receiver operator characteristic curve analysis, showing prediction capability statistically equivalent to uncontrolled trials. Compared to uncontrolled trials, controlled trials resulted in smaller thermal ablation regions and higher contrast between echo decorrelation in treated vs. untreated regions. These results indicate that control using echo decorrelation imaging may reduce treatment duration and increase treatment reliability for in vivo thermal ablation.

Low Intensity Focused Ultrasound (LOFU)-mediated Acoustic Immune Priming and Ablative Radiation Therapy for in situ Tumor Vaccines

Focal ablative therapies have been primarily used for local tumor ablation. However, they often fail to impact systemic disease. Here we propose the use of low intensity focused ultrasound (LOFU), a noninvasive, nontoxic, conformal therapy, to deliver acoustic stress to the tumor for immune priming. We demonstrate that LOFU significantly induces expression and cell surface localization of heat shock proteins in murine breast (4T1) and prostate adenocarcinoma (TPSA23) cancer cell lines. In vivo LOFU followed by ablative radiation therapy (RT) results in primary tumor cure, upregulation of a cytotoxic immune response and induction of immunological memory by inhibiting secondary tumor growth upon re-challenge with tumor cells. We, therefore, describe a regimen of a combination therapy with noninvasive, acoustic immune priming and ablative radiation therapy to generate an in situ tumor vaccine, induce CD8+ T cells against tumor-associated antigens and provide a viable oncologic treatment option for solid tumors.

Re: Impact of Tumor Size on Cancer-Specific Mortality Rate after Local Tumor Ablation in T1a Renal-Cell Carcinoma.

Re: Impact of Tumor Size on Cancer-Specific Mortality Rate after Local Tumor Ablation in T1a Renal-Cell Carcinoma.

Stereotactic body radiotherapy versus percutaneous local tumor ablation for early-stage non-small cell lung cancer

ObjectivesTo compare patterns of care and overall survival (OS) between stereotactic body radiotherapy (SBRT) and percutaneous local tumor ablation (LTA) for non-surgically managed early-stage non-small-cell lung cancer (NSCLC). Materials and methodsThe National Cancer Database (NCDB) was queried from 2004 to 2014 for adults with non-metastatic, node-negative invasive adenocarcinoma or squamous cell carcinoma of the lung with primary tumor size ≤5.0 cm who did not undergo surgery or chemotherapy and received SBRT or LTA. Patterns of care were assessed with multivariate logistic regression. After propensity-score weighting with generalized boosted regression, OS was assessed with univariate and doubly-robust multivariate Cox regression. ResultsOf 15,792 patients, 14,651 (93%) received SBRT and 1141 (7%) received LTA. Increasing age (OR 1.01, p = .035), treatment at an academic institution (OR 2.94, p < .001), increasing tumor size (OR 1.05, p < .001), and more recent year of diagnosis (OR 1.43, p < .001) were predictive of treatment with SBRT, whereas comorbidities (OR 0.74, p = .003) and treatment at a high-volume facility (OR 0.05, p < .001) were predictive for LTA. At a median follow-up of 26.2 months, SBRT was associated with improved OS relative to LTA within a propensity-score weighted doubly-robust multivariate analysis (HR 0.71, p < .001). On weighted subgroup analyses, improved OS was observed with SBRT for tumor sizes >2.0 cm (HR 0.72, p < .001) and for those treated at high-volume facilities (HR 0.71, p < .001). No OS difference was found with SBRT or LTA in tumor sizes ≤2.0 cm (HR 0.90, p = .227). ConclusionWithin the NCDB, SBRT was more commonly utilized and was associated with improved OS when compared to percutaneous LTA for patients with non-surgically managed early-stage NSCLC. Patients with small tumor volumes likely represent an appropriate population for future prospective randomized comparisons between SBRT and LTA.