Argon-helium Cryoablation Research Articles

Efficacy of argon-helium cryoablation combined with chemotherapy in the treatment of advanced NSCLC.

To explore the efficacy of argon-helium cryoablation (AHC) combined with chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). A retrospective study was carried out between February 2020 to June 2022 of 85 patients with advanced NSCLC admitted to Tianjin Cancer Hospital Airport Hospital. Patients were categorized into two groups based on whether they had received AHC: patients received chemotherapy treatment alone (chemotherapy group, n=41); patients received chemotherapy combined with AHC (combined group, n=44). Tumor control rate, serum tumor marker levels, quality of life, and median survival time between the two groups were compared. Tumor control rate in the combined group (86.36%) was significantly higher than that in the chemotherapy group (68.29%) (P<0.05). After treatment, the levels of serum cytokeratin 19 fragment (CYFRA21-1), carcinoembryonic antigen (CEA) and glycoprotein antigen 125 (CA125) in the two groups were significantly lower than those before the treatment, and significantly lower in the combined group compared to the chemotherapy group (P<0.05). After the treatment, the quality of life of patients in both groups was significantly higher than before the treatment. Quality of life in the combined group was significantly higher than in the chemotherapy group (P<0.05). One year after treatment, the median survival time of the combined group (10.5 months; 95% CI: 9.775-11.225) was significantly higher than that of the chemotherapy group (9.4 months; 95% CI: 8.55-10.323) (P=0.045). Compared with chemotherapy alone, conventional chemotherapy combined with AHC in the treatment of advanced NSCLC can significantly reduce the levels of serum tumor markers and improve overall treatment efficacy, quality of life and 1-year overall survival rate.

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]

Argon-Helium Cryoablation for Cutaneous Squamous Cell Carcinoma in the Elderly.

Cutaneous squamous cell carcinoma (cSCC) is a common type of malignant neoplasm in non-melanoma skin cancer (NMSC). Most cases of simple cSCC are considered curable by surgical removal of the lesion. However, clinical treatments for cSCC with medium- or large-sized lesions are difficult. Meanwhile, the effectiveness of the treatments is not guaranteed, especially for elderly patients, because of an intolerance to surgical resection or other adjuvant modalities. In such cases, safe and effective treatments with excellent aesthetic outcomes are urgently needed. In this study, we reported 6 elderly cSCC patients with medium- or large-sized lesions treated with argon–helium cryoablation. The average age of all 6 patients was 78 years (range 72–85 years). They were all diagnosed with cSCC with a median tumor size of 5.8 cm (range 2.5–15.5 cm) and dermal invasion. Complete ablation was achieved in all cases after a single ablation session (2 freeze–thaw cycles). Patients experienced mild pain and hemorrhage after ablation, but the symptoms were manageable. One patient developed infection and fever because of extensive necrosis of the tumor, which was eventually cured after treatment. All patients obtained good cosmetic outcomes, and their quality of life improved significantly. In the 5-year follow-up study, 4 patients were alive while 2 patients died of unrelated diseases 3 years after cryotherapy. None of the 6 patients had a recurrence. These results suggested the feasibility of argon–helium cryoablation as a novel therapeutic strategy for elderly cSCC with medium- or large-sized lesions.

Percutaneous Argon-Helium Cryoablation for Small Hepatocellular Carcinoma Located Adjacent to a Major Organ or Viscus: A Retrospective Study of 92 Patients at a Single Center.

BackgroundCryoablation of hepatocellular carcinoma (HCC) close to major organs or viscus is challenging because it can cause complications. This retrospective study aimed to investigate the safety and efficacy of percutaneous argon-helium cryoablation of small HCC located adjacent to major organs or viscus.Material/MethodsNinety-two patients who underwent percutaneous argon-helium cryoablation between February 2012 and December 2018 at the Fifth Medical Center of the Chinese People’s Liberation Army General Hospital were included. Treatment efficacy was evaluated by magnetic resonance imaging or triphasic computed tomography scan within 1 week after each cryoablation procedure. Local tumor progression, distant recurrence, and overall survival were analyzed using the Kaplan-Meier method and log-rank test.ResultsA total of 92 patients with small HCC located adjacent to major organs or viscus who underwent cryoablation were retrospectively reviewed. The number of patients with tumors adjacent to the gallbladder, portal or hepatic vein, diaphragm, stomach, heart, and intestine was 22, 1, 39, 6, 8, and 16, respectively. Cumulative local tumor progression rates at 1 and 2 years were 2.8% and 7.3%, respectively. Cumulative distant recurrence rates at 1, 2, and 3 years were 11.1%, 17.6%, and 20.7%, respectively. The overall survival rates at 1, 2, and 4 years were 100%, 93.6%, and 74.9%, respectively. Major complications were observed in 5 (5.4%) patients. Minor complications were observed in 85 (92.4%) patients.ConclusionsThis experience from a single center showed that percutaneous argon-helium cryoablation was safe and effective in the management of small HCC that is located adjacent to major organs or viscus.

Co-ablation versus cryoablation for the treatment of stage III-IV non-small cell lung cancer: A prospective, noninferiority, randomized, controlled trial (RCT).

BackgroundThis study compared a co‐ablation (CA) system, which is a novel ablation device, with an argon‐helium cryoablation (AHC) system. We aimed to compare the efficacy and safety of CA and AHC for the treatment of stage III–IV non‐small cell lung cancer (NSCLC).MethodsWe conducted a multicenter randomized controlled trial (RCT) to determine whether CA was noninferior to AHC. The primary efficacy endpoints were the iceball coverage rate (ICR) and the disease control rate (DCR) one month after treatment. Noninferiority was declared if the lower limit of two‐sided 95% confidence interval (CI) was less than 10%. The ICR and DCR were identified by logistic regression. Treatment safety was assessed.ResultsA total of 81 patients underwent randomization (41 assigned to the CA and 40 assigned to the AHC groups)and transthoracic ablation. The ICRs in the CA and AHC groups were 99.24% ± 2.18% and 98.66% ± 3.79%, respectively. Central lesions were associated with an increased risk of an incomplete ICR. The DCRs in the CA and AHC groups were 97.6% and 95%, respectively. A smaller lesion area in the CA group was significantly correlated with a better DCR. The rate of complications was 29.26% in the CA group and 30% in the AHC group. (P = 0.943). There was less probe usage per patient in the CA group.ConclusionsWe determined that CA is noninferior to AHC in terms of efficacy and safety for the treatment of stage III–IV NSCLC. A smaller lesion area in the CA group was significantly correlated with a better DCR.Key points CA was noninferior to AHC for stage III–IV NSCLC.

Computed tomography-guided argon-helium cryoablation for sacrum chordoma.

We examined the therapeutic effects of argon-helium cryoablation guided by computed tomography (CT) in the treatment of sacral chordoma.This is a retrospective study. CT-guided argon-helium cryoablation was used to treat 9 sacral chordoma patients at our centers between January 2016 and June 2019. We collected data on treatment response and success. Data from long-term follow-up of treatment outcomes were also assessed.All patients were treated successfully according to the indicated technical parameters. There were no reports of procedure-related complications from any of the patients. Complete response (CR) was also achieved in all patients. Six patients (66.7%) achieved initial CR after 1 treatment session and 3 patients (33.3%) achieved secondary CR after 2 treatment sessions. The chordoma-related symptoms improved significantly in all patients after treatment. The mean visual analogue scale score improved from 7.3 before treatment to 4.2 after treatment (P < .001). The mean function score improved from 3.2 before treatment to 1.4 after treatment (P < .001). The median length of follow-up for all patients was 33 months (range: 6–46 months). All patients were alive during the follow-up. Two (22.2%) patients experienced local recurrence (LR) at 6 and 9 months after treatment, respectively. These patients had revised treatment with trans-arterial embolism (n = 1) or repeat ablation (n = 1). The median progression-free survival was 36.8 months.Treatment of sacral chordoma with CT-guided argon-helium cryoablation is effective and offers a potentially beneficial therapeutic alternative for patients with the condition.

Efficacy of argon-helium cryoablation and its effects on immune function of patients with neck malignant tumours.

Our study aimed to investigate the clinical efficacy of argon-helium cryoablation and its effects on the immune function of patients with neck malignant tumours. Retrospective study. Single-institution academic tertiary care centre. Totally, 180 patients harbouring head and neck malignant tumours were divided into the argon-helium cryoablation group (n=150) and the radiotherapy group (n=50). The efficacy of the two groups was compared, and the immune function was observed. The short-term clinical effect of the argon-helium cryoablation group was significantly higher than that of the radiotherapy group (P<.05). After treatment, the CD3+, CD4+, CD8+ and CD4+/CD8+ of the argon-helium cryoablation group were significantly better than those of the radiotherapy group (P<.001). The results of TNF-α, IL-1 β and CRP in the argon-helium cryoablation group were significantly better than that in the radiotherapy group (P<.001). Argon-helium cryoablation could effectively improve the immune function, 5-year survival rate and local remission rate.

MP70-15 PRECISE PROSTATE CRYOTHERAPY GUIDED BY MAGNETIC RESONANCE IMAGING AND 99MTC-PSMA SPECT/CT

You have accessJournal of UrologyProstate Cancer: Localized: Ablative Therapy II (MP70)1 Apr 2020MP70-15 PRECISE PROSTATE CRYOTHERAPY GUIDED BY MAGNETIC RESONANCE IMAGING AND 99MTC-PSMA SPECT/CT Guo-Wen Lin* Guo-Wen Lin*Guo-Wen Lin* More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000950.015AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cryotherapy can effectively control tumor lesions, relieve symptoms and improve patients' quality of life by killing tumor cells at low temperature. The 99mTc-PSMA SPECT/CT examination has high specificity, sensitivity and cost performance for prostate cancer. This study explored the value of precision magnetic resonance imaging and 99mTc-PSMA SPECT/CT guided precision prostate cryotherapy in early localized prostate cancer. METHODS: We retrospectively collected data from 20 patients with localized prostate cancer who underwent prostate cryotherapy from October 2017 to October 2018. Preoperative pelvic magnetic resonance imaging (MR) and 99mTc-PSMA SPECT/CT were performed to assess the location of lesions and its size. Argon-helium cryoablation technique was used. The intraoperative ultrasound guided the 1.47mm diameter probe into the prostate through the perineum. The argon gas formed the needle tip into a spherical ice hockey with a diameter of 2cm and the ice hockey cooled to -140∼-170°C, after 10-15 minutes, the argon gas was turned off, and then the helium gas was started to rapidly raise the local temperature to 20∼40°C for 3 minutes, and two cycles were performed to completely damage the diseased tissue. Postoperative follow-up was used to assess changes in PSA and imaging. RESULTS: Evaluation of lesions using images, combined with intraoperative ultrasound real-time images. All patients accurately located the lesion location and size, and ice hockey range prostate tissue should be included as much as possible, and at least 1 needle complete including tumor lesions. PSA was reviewed 1 month after cryotherapy, suggesting that the median value was 10.3 ng/mL (45.5% reduction). Three months later, 18 patients underwent MR and/or 99mTc-PSMA SPECT/CT, showing the lesion disappeared completely for 4 cases, 14 patients' local lesions were clearly controlled. Common postoperative adverse reactions included short-term dysuria (6/20, 30%), lower abdominal distension (4/20, 20%), hematuria (1/20, 5%), and local necrosis of the urethra (1/20, 5%). CONCLUSIONS: Prostatic cryotherapy is effective for patients with a life expectancy of <10 years or an early stage of surgery that is not suitable for surgery. The examination of MR and/or 99mTc-PSMA SPECT/CT can guide the precise positioning and treatment of prostate cryopreservation, and has great clinical value. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1060-e1061 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Guo-Wen Lin* More articles by this author Expand All Advertisement PDF downloadLoading ...

Efficacy and Safety of Percutaneous Argon-Helium Cryoablation for Hepatocellular Carcinoma Abutting the Diaphragm.

To evaluate the efficacy and safety of percutaneous argon-helium cryoablation (CA) for hepatocellular carcinoma (HCC) abutting the diaphragm (<5 mm). A total of 61 consecutive patients (50 men, 11 women; mean age, 56.3 ± 12.1 years old; range, 32-83 years) with 74 HCC tumors (mean size, 3.3 ± 1.7 cm; range, 0.8-7 cm) who were treated with percutaneous argon-helium CA were enrolled in this retrospective study. Adverse events were evaluated according to Common Terminology Criteria for Adverse Events, version 5.0. Local tumor progression (LTP) and overall survival (OS) were analyzed using the Kaplan-Meier method and the log-rank test. The risk factors associated with OS and LTP were evaluated using univariate and multivariate Cox regression analysis. No periprocedural (30-day) deaths occurred. A total of 29 intrathoracic adverse events occurred in 24 of the 61 patients. Major adverse events were reported in 5 patients (pleural effusion requiring catheter drainage in 4 patients and pneumothorax requiring catheter placement in 1 patient). Median follow-up was 18.7 months (range, 2.3-60.0 months). Median time to LTP after CA was 20.9 months (interquartile range [IQR], 14.1-30.6 months). Median times of OS after CA and diagnosis were 27.3 months (IQR, 15.1-45.1 months) and 40.9 months (interquartile range, 24.8-68.6 months), respectively. Independent prognostic factors for OS included tumor location (left lobe vs right lobe; hazard ratio [HR], 2.031; 95% confidence interval [CI], 1.062-3.885; P= .032) and number of intrahepatic tumors (solitary vs multifocal; HR, 2.684; 95% CI, 1.322-5.447; P= .006). Independent prognostic factors for LTP included age (HR, 0.931; 95% CI, 0.900-0.963; P < .001), guidance modality (ultrasound vs computed tomography and US; HR, 6.156 95% CI, 1.862-20.348; P = .003) and origin of liver disease. Percutaneous argon-helium CA is safe for the treatment of HCC abutting the diaphragm, with acceptable LTP and OS.

Argon–helium cryoablation for liver carcinoma in high-risk locations: Safety and efficacy

Argon–helium cryoablation for liver carcinoma in high-risk locations: Safety and efficacy

Long-term survival of an elderly patient with advanced gastric cancer after combination therapy: a case report and literature review

BackgroundGastric cancer ranks the fifth most common cancer, and the third leading cause of cancer-related deaths worldwide. Gastric cancer with liver metastasis (GCLM) has devastating prognosis, however, optimal treatment of GCLM, especially in elderly patients, has yet to be clarified.Case presentationA 75-year-old man was diagnosed with advanced gastric cancer (GC), presenting with acute gastrointestinal bleeding and synchronous metastatic lesion in liver. Based on multidisciplinary team (MDT)‘s decision, this patient underwent distal palliative gastrectomy with R1 margin. Histopathological diagnosis was stage IV gastric adenocarcinoma (pT3N2M1), HER2 negative. The patient was treated with chemotherapy and argon-helium cryoablation of liver and lung metastases.HER-2 gene amplification was identified in peripheral blood at later stage of therapy. The patient had been followed-up for 39 months, in sharp contrast to a median survival time of 13.8 months for majority of advanced GC.ConclusionsPalliative distal gastrectomy in combination with chemotherapy and cryoablation significantly prolongs overall survival of an elderly patient with GCLM.

MicroRNA-647 promotes the therapeutic effectiveness of argon&amp;ndash;helium cryoablation and inhibits cell proliferation through targeting TRAF2 via the NF-&amp;kappa;B signaling pathway in non-small cell lung cancer

BackgroundMicroRNA-647 (miR-647) has been reported to repress cell tumorigenic phenotype, while the function of miR-647 in non-small cell lung cancer was obscure.MethodsThe effect of miR-647 and TRAF2 on A549 and H1299 cells was explored through Methyl thiazolyl tetrazolium (MTT) assay, colony formation and cell cycle assays. Luciferase reporter assays, reverse transcription quantitative PCR (RT-qPCR) and Western blot assay were carried out to determine that TRAF2 is directly regulated by miR-647. The effect of miR-647/TRAF2 axis on p65 protein level in nucleus or total was detected by Western blot assay.ResultsHere, we found that miR-647 was high expression in tumor that under argon-helium cryoablation treatment in contrast to the tumor under non argon-helium cryoablation treatment and inhibited cell proliferation of A549 and H1299 cells by inducing G1-S transition. TRAF2 was confirmed as a target of miR-647. TRAF2 overexpression partially rescued the suppressive function of miR-647 in A549 and H1299 cells. Moreover, we found that miR-647 repressed lung carcinogenesis by attenuating NF-κB pathway.ConclusionIn all, our study demonstrates that miR-647 functions as tumor suppressor via targeting and down-regulating the expression of TRAF2 and NF-κB signaling pathway in non-small cell lung cancer.

Clinical Investigation on CT guided cryoablation for treating invasive chest wall or pleural tumors

Objective: To evaluate the feasibility and short-term effect of CT guided cryoablation for malignant chest wall or pleural involvement. Methods: To follow up 22 patients with chest wall or pleural involvement of various malignancies who underwent cryoablation from January 2012 to January 2015 by conducting postoperative 1-, 3- and 6-month enhanced CT, MRI or PET-CT examinations, respectively, evaluate local curative effect, and observe their progression-free survival (PFS), postoperative pain remission and complications after the cryoablation. Results: A total of 22 patients with 27 lesions received 26 times of argon-helium cryoablation. According to the coverage situation of immediate postoperative ice balls on the lesions, they were divided into a complete coverage group (Group A with 18 patients) and a partial coverage group (Group B with 4 patients). 1 month later, 15 patients' tumors were completely ablated, and 3 had residue and thus received the second cryoablation in Group A, while all patients' tumors had residue in Group B. 3 months later, 17 patients' tumors were completely ablated, and 1 had residue and thus received another cryoablation in Group A, while all patients' residual tumors enlarged in different extent in group B. 6 months later, all lesions were ablated in group A while all patients' residual tumors enlarged in group B. For the 22 patients, their preoperative, and postoperative 1-week, 1-month, 3-month, and 6-month VAS scores were 4.95±0.57, 1.45±0.35, 1.45±0.35, 1.64±1.71, and 2.00±2.35, respectively. The differences in the preoperative, postoperative 1-week, and postoperative 1-month scores are significant statistically (P<0.05), and the difference in the postoperative 1-month and 6-month scores is also with statistical significance (P=0.03). For all patients, their post-operative 1-week, 1-month, 3-monte and 6-month pain remission rates are 90.9%(20/22), 90.9%(20/22), 86.4% (19/22)and 81.8%(18/22), respectively. With a median follow-up of 13.5 months, the median PFS is 7 months. The adverse effect after argon-helium cryoablation involved transitory worsened pain (16 cases), pleural effusion (5 cases, including 3 underwent closed drainage), fever (5 cases), and hemoptysis (3 cases). Conclusion: CT guided argon-helium cryoablation is a safe and effective method to treat malignant chest wall or pleural involvement.

The value of 64-slice spiral CT perfusion imaging in the treatment of liver cancer with argon-helium cryoablation.

We analyzed the effectiveness of using 64-slice spiral computed tomography (CT) and perfusion imaging to guide argon-helium cryoablation treatment of liver cancer. In total, 60 cases of advanced hepatocellular carcinoma before surgery treated with argon-helium cryoablation were inlcuded in the present study. Retrospective summary of the 60 cases of metaphase and advanced liver cancer were used as the control group. The control group were treated using cryoablation with argon-helium knife. We used enhanced scanning with 64-slice spiral CT to define the extent of their lesions and prepared a plan of percutaneous cryoablation for the treatment. Intraoperatively, we used the dynamics of CT perfusion imaging to observe the frozen ablation range and decreased the rate of complications. After surgery, the patients were followed-up regularly by 64-slice CT. We used conventional X-ray, CT and magnetic resonance imaging (MRI) for pre-operative lateralization. Intraoperative X-ray or ultrasound guidance and follow-up with CT or MTI were added to determine the clinical effectiveness and prognosis. The results showed that the total effective rate was improved significantly and incidence rate of overall complications decreased markedly in the observation group. Following treatment, AFP decreased significantly while the total freezing area and time were reduced significantly. The median survival time was increased significantly in the observation group. The numeric values of hepatic arterial perfusion, portal vein perfusion and hepatic arterial perfusion index were all markedly lowered after treatment. Differences were statistically significant (P<0.05). In conclusion, the use of 64-slice spiral CT perfusion imaging may considerably improve the effects of liver cancer treatment using the argon-helium cryoablation. It extended the survival time and reduced complications.

Using 3.0 T MR to dynamically observe ablated lung tumors after percutaneous cryotherapy therapy

Objective: To initially explore MRI features and its changing trends including of lung tumors after Argon-Helium cryoablation therapy, and enhance the recognition of MR findings of lung tumors postcryoablation. Methods: Twenty-three cases of patients with twenty six nodules of pulmonary malignance who received Argon-Helium cryoablation therapy in Henan Cancer Hospital from July 2014 to January 2016 were enrolled.All patients underwent unenhanced and dynamic contrast-enhanced MRI scans at pre-and 1-day, 1-week, 1-, 3-, 6-, 12-month postcryoablation. Two radiologists independently reviewed MRI images, signal intensity in the ablated zone on T1WI and T2WI were assessed by a 5-point scale.The changing trends of size and signal intensity with time were showed by time-maximum diameter and time-score curve.Time-signal intensity curves based on dynamic enhanced sequence were also performed. Results: Typical MRI findings includes: heterogeneous signal intensity on both T1WI and T2WI at 1-day postcryoablation(26/26, 100%). Hyper-intense on T1WI(22/26, 84.6%) and T2WI(17/26, 65.4%) with a hypo-intense rim at 1-week postcryoablation.Decreasing signal intensity on T1WI(17/26, 65.4%) and increasing signal intensity on T2WI(22/26, 84.6%) at 1-month.Signal intensity declined to the level of muscle on both T1WI(18/26, 69.2%) and T2WI(19/26, 73.1%) at 3-month, nineteen ablated zone turned into patchy shape(19/26, 73.1%). The maximum diameter was largest at 1-day and gradually shrunk with time. The mean score value toped at 1-week and gradually decreased. A straight line type without definite enhancement was found from 1-day to 1-month postcryoablation, an inflow curve with a mild delayed enhancement was seen from 3- to 12- month. Totally 4 recurrence (4/26, 15.4%) all occurred at 3-month and were lack of a complete hypo-intense rim at 1-week postcryoablation. Conclusion: MRI findings of lung tumors postcryoablation are characteristic, a complete hypo-intense rim at 1-week is helpful to determine further recurrence, 1-week to 3-month is an important period to observe significant change of the ablation zone, MRI is valuable in identifying the ablation zone and can reflect its evolution with time.

Functional Changes of Dendritic Cells in C6 Glioma-Bearing Rats That Underwent Combined Argon-Helium Cryotherapy and IL-12 Treatment.

The aim of this study was to explore changes in tumor tissues of glioma-bearing rats that underwent argon-helium cryoablation as well as changes in antitumor immunity before and after combined interleukin 12 treatment. Two hundred sixty Wistar rats were randomly divided into a blank control group, intravenous injection interleukin-12 group, cryotherapy group, and cryotherapy + intravenous injection group. C6 glioma cells proliferated in vitro were implanted subcutaneously on the backs of rats to establish C6 glioma-bearing animal models. Each group underwent the corresponding treatments, and morphological changes in tumor tissues were examined using hematoxylin-eosin staining. CD11c staining was examined using immunohistochemistry, and differences in dendritic cells and T-cell subsets before and after treatment were analyzed using flow cytometry. The control group showed no statistical changes in terms of tumor tissue morphology and cellular immunity, cryotherapy group, and cryotherapy + intravenous injection group, among which the count for the cryotherapy + intravenous injection group was significantly higher than those of all other groups. In the argon-helium cryotherapy group, tumor cells were damaged and dendritic cell markers were positive. The number of CD11c+ and CD86+ cells increased significantly after the operation as did the cytokine interferon-γ level (P < .01), suggesting a shift toward Th1-type immunity. Combined treatment of argon-helium cryoablation and interleukin 12 for gliomas not only effectively injured tumor tissues but also boosted immune function and increased antitumor ability. Therefore, this approach is a promising treatment measure for brain gliomas.

Analysis of therapeutic effectiveness and prognostic factor on argon-helium cryoablation combined with transcatheter arterial chemoembolization for the treatment of advanced hepatocellular carcinoma.

The objective of this study was to evaluate the effectiveness on argon-helium cryoablation combined with transcatheter arterial chemoembolization (TACE) in treating advanced hepatocellular carcinoma (HCC) and its influence factor. This trial was approved by the Guangzhou Panyu Central Hospital Ethics Committee. This was a prospective, single-center study conducted in Guangzhou Panyu Central Hospital. After informed consent was obtained, the prospective randomized clinical data of 120 patients with advanced HCC were collected. Based on the therapeutic scheme, the patients were divided into control group (TACE + argon-helium cryoablation) and observed group (TACE group). All the patients were followed up for 60 months. The pre- and post-operative cancer situation, hepatic function situation, complete remission (CR) rate, total effective rate, and survival time were evaluated. The short-term and long-term effectiveness were compared between the two groups. Both the CR rate and total effective rate of the combination group were significantly higher than those of TACE group (P < 0.05). Liver function damage of the combination group was lower than those of TACE group. The survival rate of the combination group was significantly longer than that of TACE group P < 0.05). The Cox regression model revealed that ages, tumor diameter, tumor periportal location, and liver function (Child-Pugh) were significant variables influencing survival time P < 0.05). For the treatment of advanced HCC, argon-helium cryoablation combined with TACE is obviously effective and safe. The ages, tumor diameter, tumor periportal location, and grade of liver function (Child-Pugh) have obvious impacted the treatment effectiveness.

4SCAR19 Chimeric Antigen Receptor-Modified T Cells As a Breakthrough Therapy for Highly Chemotherapy-Resistant Late-Stage B Cell Lymphoma Patients with Bulky Tumor Mass

▪Background: Chemo-resistant, advanced B cell lymphomas with bulky tumor are difficult to treat and often fatal. Recent studies have shown that CD19 chimeric antigen receptor-engineered T (CAR-T) cells can effectively treat B-cell malignancies. However, CAR-T therapy-associated adverse systemic responses including fever, tachycardia, profound hypotension, and respiratory distress, can be life-threatening. The toxicities of CAR-T infusion are directly correlated with tumor burden, disease sites and other complications during treatment. Therefore, highly individualized CAR-T therapy regimen is key to the success of such innovative treatment.Patients and Methods: In this phase I/II multi-center CAR-T therapy trial, we have evaluated 13 patients (pts) with chemo-resistant B cell lymphomas, including 12 advanced diffuse large B cell lymphomas (DLBCL) and 1 Burkitt's lymphoma, average age 37 (range 9-61), stage IIIA/IVB. Twelve of them had bulky tumor and met the criteria of high-risk by the second-line age-adjusted international prognostic index (sAAIPI) and were associated with the following co-morbidities: Aspergillus invasive fungal infection (IFI) pneumonia (2), drug-induced liver injury (2), pleural pericardial cavity effusion (2), hepatitis B (2), diabetes mellitus (1), gastrointestinal hemorrhage (1), deep venous thrombosis (1), and lung tumor argon-helium cryoablation surgery (1). Autologous T cells were apheresis collected and lentivirally transduced with a 4th generation, apoptosis-inducible, safety-engineered CAR: CD19- scFv/CD28/CD137/CD27/CD3ζ-iCasp9 (4SCAR19). All pts received conditioning regimen of cyclophosphamide 250 mg/m2/d x3d, and fludarabine 30 mg/m2/d x3d, followed by 1 to 3 infusions of CAR-T cells in a dose range of 0.45- 4.59 x106 cells/kg per infusion.Results: The lentiviral 4SCAR19 transduction efficiencies were in the range of 5-100%. Patient response did not always correlate with CAR gene transfer efficiencies, but instead, correlated better with the condition of the T cells. Eight pts have achieved complete tumor regression (CR) for 3 to 10 months, with stable CAR DNA copies of 0.1-0.4% in the blood. Three pts achieved dramatic tumor reduction but died from various causes including: intracranial hemorrhage due to low platelet count, pre-existing ureteral obstruction/acute renal failure and cardiopulmonary complications, with or without severe cytokine release syndrome (CRS) at day 29, 28 and 66 after CAR-T infusion, respectively. Two pts died from progressive diseases. Treatment toxicities included CRS with fever over 39o C (9/13), massive hemorrhage of the alimentary tract (1/13) and severe myelo-suppression (3/13), which were correlated with increased plasma cytokines including IL-6 and IFN-γ. The 120 day disease-free survival (DFS) rate is 53% (CI, 36-69%), and the 10 month overall survival probability is 55% (CI, 39-74%).Conclusion and discussion: While 4SCAR19 T cells can relieve severe disease symptoms and obtain dramatic tumor control even in late-stage, highly chemo-resistant, bulky tumor-bearing pts, our studies suggest that in order to obtain favorable and durable clinical outcomes in the late-stage pts, the optimal timing for CAR-T engagement, a highly individualized chemo-regimen, and better clinical management for CRS and pre-existing health conditions are critical. While long-term follow-up and better understanding of the tumor genotype and immunobiology are needed, our study indicates that a highly experienced clinical management team is key to the success of CAR-T therapy for advanced B cell lymphomas. DisclosuresDong:America Yuva Biomed: Consultancy. Kuo:America Yuva Biomed: Employment. Liu:America Yuva Biomed: Employment.

Synergism between cryoablation and GM-CSF: enhanced immune function of splenic dendritic cells in mice with glioma.

Glioma is the most common malignant primary brain tumor, and it has a poor prognosis. Studies have shown that cryoablation can activate antitumor immunoeffects by promoting the augmentation of dendritic cells (DCs). Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to be useful for immunotherapy against glioma because it can stimulate DCs to present tumor antigen. Previous studies have shown that cryoablation and GM-CSF can exert antitumor effects. To test the hypothesis that combined therapy with cryoablation and GM-CSF for glioma could synergistically improve specific antiglioma immunity in mice, we tested the validity of this assumption in a murine subcutaneous GL261 glioma model. C57BL/6 mice with subcutaneous GL261 glioma were created and divided into four groups: no treatment, GM-CSF injection, cryoablation treatment, and GM-CSF and cryoablation combined treatment (n=20 in each group). Serial immune indicators were detected at sequential time points during treatment. Compared with the other groups, in the combined treatment group, DCs were more activated and their numbers were markedly upregulated, the secretion of interferon-γ from Th1 cells of mice spleen was increased, and the cytolytic activity of CD8 CTLs exerted a more significant cytotoxic effect on GL261 glioma cells (P<0.05 for all). Furthermore, these changes peaked on the 7th day after treatment, and then gradually reduced, until the 21st day; these changes were higher than those at pretreatment (P<0.05). It is concluded that combined therapy with argon-helium cryoablation and GM-CSF could synergistically enhance the activation of DCs and induce a robust tumor-specific immunologic response in glioma-bearing mice.

Magnetic resonance imaging-navigated argon-helium cryoablation therapy against a rabbit VX2 brain tumor.

The aim of the present study was to investigate the feasibility of interventional magnetic resonance imaging (MRI)-guided and monitored argon-helium cryoablation for the treatment of brain tumors in rabbits. In addition, the present study evaluated the associations between imaging and pathology, the therapeutic effects and the effects on the surrounding normal tissues. A total of 14 rabbits were equally divided into groups C and D. Under general anesthesia, the skull was drilled and tumor blocks were implanted. Subsequently, a New Zealand rabbit VX2 brain tumor model was successfully established. Rabbits in group C were treated with argon-helium cryoablation and those in group D did not undergo any treatment (control). Regular postoperative MRI scanning was performed to observe the changes in tumor size, and the survival times of the rabbits in groups C and D were recorded. The extent of necrosis in the brain tumor exhibited a significant correlation with the freezing time of cryoablation, and the necrotic region was shown to be the same size as the ice ball. The survival times of the rabbits in the treatment group (group C) were significantly prolonged. Therefore, the observations of the present study demonstrated that the VX2 brain tumor model, produced using an improved tumor block implantation method, was stable and suitable for MRI observation and interventional study. In addition, argon-helium cryoablation was shown to be a safe and feasible therapeutic method for the treatment of brain tumors, and was demonstrated to significantly increase the survival times of the brain tumor-bearing rabbits.