Image-guided Locoregional Therapies Research Articles

Interventional Oncology Meets Immuno-oncology: Combination Therapies for Hepatocellular Carcinoma.

The management of hepatocellular carcinoma (HCC) is undergoing transformational changes due to the emergence of various novel immunotherapies and their combination with image-guided locoregional therapies. In this setting, immunotherapy is expected to become one of the standards of care in both neoadjuvant and adjuvant settings across all disease stages of HCC. Currently, more than 50 ongoing prospective clinical trials are investigating various end points for the combination of immunotherapy with both percutaneous and catheter-directed therapies. This review will outline essential tumor microenvironment mechanisms responsible for disease evolution and therapy resistance, discuss the rationale for combining locoregional therapy with immunotherapy, summarize ongoing clinical trials, and report on developing imaging end points and novel biomarkers that are relevant to both diagnostic and interventional radiologists participating in the management of HCC.

Role of Interventional Radiology in Managing Primary and Metastatic Breast Cancer.

Percutaneous image-guided locoregional therapies are emerging in the treatment of primary and metastatic breast cancer. Cryoablation has emerged as the dominant ablative approach as an alternative to surgery for primary breast cancer in patients who do not wish to have surgery or are poor surgical candidates. Cryoablation is well tolerated and provides excellent local control and cosmesis. Thermal ablation may also be used in the treatment of oligometastatic breast cancer, allowing patients to achieve long disease-free intervals. Transarterial therapies have been studied in the treatment of oligoprogressive hepatic metastasis, though further supportive data would be helpful to demonstrate its efficacy.

Indian College of Radiology and Imaging Guidelines on Interventions in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and a significant cause of cancer-related death. Treatment of HCC depends on the stage of the tumor. As many patients with HCC are not deemed fit for surgical resection or liver transplantation, locoregional therapies play an essential role in the management. Image-guided locoregional treatments include percutaneous ablative therapies and endovascular therapies. The choice of an individual or a combination of therapies is guided by the tumor and patient characteristics. As the outcomes of image-guided locoregional treatments depend on the ability to achieve necrosis of the entire tumor along with a safety margin around it, it is mandatory to follow standard guidelines. In this manuscript, we discuss in detail the various aspects of image-guided locoregional therapies to guide interventional radiologists involved in the care of patients with HCC.

Effect of CRISPR Knockout of AXIN1 or ARID1A on Proliferation and Migration of Porcine Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is an aggressive disease lacking effective treatment. Animal models of HCC are necessary for preclinical evaluation of the safety and efficacy of novel therapeutics. Large animal models of HCC allow testing image-guided locoregional therapies, which are widely used in the management of HCC. Models with precise tumor mutations mimicking human HCC provide valuable tools for testing precision medicine. AXIN1 and ARID1A are two of the most frequently mutated genes in human HCC. Here, we investigated the effects of knockout of AXIN1 and/or ARID1A on proliferation, migration, and chemotherapeutic susceptibility of porcine HCC cells and we developed subcutaneous tumors harboring these mutations in pigs. Gene knockout was achieved by CRISPR/Cas9 and was validated by Next Generation Sequencing. AXIN1 knockout increased the migration of porcine HCC cells but did not alter the cell proliferation. Knockout of ARID1A increased both the proliferation and migration of porcine HCC cells. Simultaneous knockout of AXIN1 and ARID1A increased the migration, but did not alter the proliferation of porcine HCC cells. The effect of gene knockout on the response of porcine HCC cells to two of the most commonly used systemic and locoregional HCC treatments was investigated; sorafenib and doxorubicin, respectively. Knockout of AXIN1 and/or ARID1A did not alter the susceptibility of porcine HCC cells to sorafenib or doxorubicin. Autologous injection of CRISPR edited HCC cells resulted in development of subcutaneous tumors in pigs, which harbored the anticipated edits in AXIN1 and/or ARID1A. This study elucidates the effects of CRISPR-mediated knockout of HCC-associated genes in porcine HCC cells, and lays the foundation for development and utilization of genetically-tailored porcine HCC models for in vivo testing of novel therapeutic approaches in a clinically-relevant large animal model.

Interventional Radiology Image-Guided Locoregional Therapies (LRTs) and Immunotherapy for the Treatment of HCC.

Simple SummaryInterventional radiology image-guided locoregional therapies for the treatment of HCC have demonstrated to be characterized by immunomodulatory effects on the tumoral microenvironment, and, possibly, systemic. Immunotherapy has gained an important role in the treatment of HCC over the last several years. Currently, there is great interest in combining locoregional therapies with immunotherapy, as this could open a new chapter in the history of HCC treatment. In this review, after describing the immune system changes caused by the tumor, we describe, for each locoregional therapy, technique and immunomodulatory effects. Then, we describe the current status of immunotherapy in HCC and report the ongoing clinical studies testing the combination treatment.Image-guided locoregional therapies (LRTs) are a crucial asset in the treatment of hepatocellular carcinoma (HCC), which has proven to be characterized by an impaired antitumor immune status. LRTs not only directly destroy tumor cells but also have an immunomodulating role, altering the tumor microenvironment with potential systemic effects. Nevertheless, the immune activation against HCC induced by LRTs is not strong enough on its own to generate a systemic significant antitumor response, and it is incapable of preventing tumor recurrence. Currently, there is great interest in the possibility of combining LRTs with immunotherapy for HCC, as this combination may result in a mutually beneficial and synergistic relationship. On the one hand, immunotherapy could amplify and prolong the antitumoral immune response of LRTs, reducing recurrence cases and improving outcome. On the other hand, LTRs counteract the typical immunosuppressive HCC microenvironment and status and could therefore enhance the efficacy of immunotherapy. Here, after reviewing the current therapeutic options for HCC, we focus on LRTs, describing for each of them the technique and data on its effect on the immune system. Then, we describe the current status of immunotherapy and finally report the recently published and ongoing clinical studies testing this combination.

Radioembolization for Hepatocellular Carcinoma

AbstractHepatocellular carcinoma (HCC) is the fastest-growing cancer worldwide, causing significant morbidity and mortality. Surgical resection, ablation, or transplantation is the best treatment option for patients with HCC. However, only about one-fifth of patients are suitable for such primary curative treatments due to underlying liver disease or rapid extension of the tumor. Image-guided locoregional therapies may prove an important alternative in this scenario, particularly transarterial radioembolization (TARE) with yttrium-90 (Y-90). Based on many studies, TARE can be considered a curative treatment option for patients with early-stage HCC, a bridge to transplantation, and a method for downstaging tumors to give patients with unresectable HCC a chance to potentially receive a curative treatment. TARE can be also combined with other treatment modalities to provide a better quality of life in patients when compared with systemic therapy in patients with unresectable HCC. Here, we discuss the use of TARE in the approach to HCC patients who are in early, intermediate, or advanced stages.

Therapy of Intermediate-Stage Hepatocellular Carcinoma: Current Evidence and Clinical Practice.

Intermediate-stage Hepatocellular Carcinoma (HCC) represents a wide range of disease burden. Patients with different levels of liver function, tumor size, and number of lesions may all have intermediate-stage disease according to the Barcelona Clinic Liver Cancer (BCLC) staging system. Several minimally invasive image-guided locoregional therapies are available for the treatment of intermediate-stage HCC, including conventional transarterial chemoembolization (cTACE), drug-eluting bead TACE (DEB-TACE), yttrium-90 radioembolization (Y-90 RE), thermal ablation, bland embolization, and combination therapy. Available clinical evidence points to cTACE as the current gold standard for the locoregional treatment of intermediate-stage HCC. DEB-TACE is at best non-inferior to cTACE in terms of survival benefit. Y-90 RE is a maturing therapy, and some institutions have adopted it as first-line therapy for intermediate-stage HCC. Thermal ablation combined with TACE may be used in select patients, while bland embolization has only limited evidence for its use. The combination of locoregional therapy with VEGF inhibitors or immune checkpoint inhibitors has also been explored. This article will examine in detail the clinical evidence supporting available locoregional treatment options for intermediate-stage HCC.

Percutaneous image-guided ablation of bone metastases: local tumor control in oligometastatic patients

Introduction: Percutaneous image-guided cryo- (CA) and radiofrequency- (RFA) ablations have been widely used in the treatment of painful bone metastases (BM). However, paucity of data is available for the performance of these treatments when used with a curative intent. The aim of this study is to investigate the local progression free-survival (LPFS) after radical percutaneous image-guided ablation of BM in oligometastatic patients, and to identify predictive factors associated with local tumor progression.Materials and Methods: This is a retrospective review of all patients who underwent percutaneous image-guided CA or RFA of BM with a radical intent between 2007 and 2018.Results: Forty-six patients with a total of forty-nine BM underwent percutaneous image-guided CA (N = 37; 75,5%) or RFA (N = 12; 24,5%). Primary malignancies included thyroid (N = 11, 22.5%), breast (N = 21; 42.9%), lung (N = 8; 16.3%) and other (N = 9; 18,3%) cancers. Additional consolidation was performed after ablation in 20.4% cases (N = 10). Mean follow-up was 34.1 ± 22 months. Local progression at the treated site was observed in 28.5% cases (N = 14); 1- and 2-year LPFS was 76.8% and 71.7%, respectively. Size of BM (>2 cm) predicted local tumor progression (p = .002).Conclusions: Percutaneous image-guided locoregional therapies used in the radical treatment of BM in oligometastatic patients demonstrate significant rates of LPFS providing the size of BM ≤2 cm.

Locoregional Therapies for Primary and Secondary Hepatic Malignancies.

Management of hepatic malignancies is a multidisciplinary task with the involvement of hepatologists, medical/surgical oncologists, transplant surgeons, and interventional radiologists. The patients should be selected for a specific targeted therapy after multidisciplinary consensus. Interventional oncology has established its role in the management of hepatic malignancies. Image-guided locoregional therapies decrease the rate of systemic toxicity without compromising tumoricidal effect.

Value of subtraction MRI in assessing treatment response following image-guided loco-regional therapies for hepatocellular carcinoma

To compare contrast-enhanced subtraction magnetic resonance imaging (MRI) with contrast-enhanced standard MRI in assessing treatment response following loco-regional therapies for hepatocellular carcinoma (HCC). Institutional review board approval was obtained and informed consent was waived for this retrospective study. All patients were analysed from our institution's liver tumour database that had loco-regional HCC therapy and the following: (1) a contrast-enhanced MRI ≤6 weeks post-treatment, (2) an unenhanced T1-weighted high-signal treatment zone (TZ) ≥1cm, (3) follow-up contrast-enhanced MRI performed ≥6 months post-treatment. Randomized standard and subtraction TZ datasets were independently assessed by three blinded radiology readers for either complete treatment necrosis or residual disease. The standard of reference (SOR) comprised a consensus read by two radiologists with knowledge of the follow-up MRI and all available clinical data. Statistical analyses were performed using receiver operating characteristics (ROC), t-test, and kappa statistic. Twenty-six patients (19 male and seven female patients; mean age 60 years, standard deviation 10.9 years, range 46-88 years) had a total of 45 corresponding HCCs and TZs. For ROC, the area under the curve (AUC) was 0.93 (subtraction protocol) versus 0.90 (standard protocol; p=0.49). For the t-test, the mean reader confidence level was 4.4, 3.6, and 4.4 (subtraction protocol) versus 3, 3, and 3.7 (standard protocol; p≤0.011). The kappa statistic for reader-to-SOR agreement was 0.83, 0.63, and 0.71 (subtraction protocol) versus 0.51, 0.36, and 0.64 (standard protocol). Subtraction MRI significantly improves the reader confidence level in the assessment of treatment response following loco-regional therapies for HCC.

Therapeutic options for intermediate-advanced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignancies, ranking the sixth in the world, with 55% of cases occurring in China. Usually, patients with HCC did not present until the late stage of the disease, thus limiting their therapeutic options. Although surgical resection is a potentially curative modality for HCC, most patients with intermediate-advanced HCC are not suitable candidates. The current therapeutic modalities for intermediate-advanced HCC include: (1) surgical procedures, such as radical resection, palliative resection, intraoperative radiofrequency ablation or cryosurgical ablation, intraoperative hepatic artery and portal vein chemotherapeutic pump placement, two-stage hepatectomy and liver transplantation; (2) interventional treatment, such as transcatheter arterial chemoembolization, portal vein embolization and image-guided locoregional therapies; and (3) molecularly targeted therapies. So far, how to choose the therapeutic modalities remains controversial. Surgeons are faced with the challenge of providing the most appropriate treatment for patients with intermediate-advanced HCC. This review focuses on the optional therapeutic modalities for intermediate-advanced HCC.