Intratumoral Immunotherapy: Is It Ready for Prime Time?

PURPOSE OF REVIEW: This review presents the rationale for intratumoral immunotherapy, technical considerations and safety. Clinical results from the latest trials are provided and discussed. RECENT FINDINGS: Intratumoral immunotherapy is feasible and safe in a wide range of cancer histologies and locations, including lung and liver. Studies mainly focused on multi-metastatic patients, with some positive trials such as T-VEC in melanoma, but evidence of clinical benefit is still lacking. Recent results showed improved outcomes in patients with a low tumor burden. Intratumoral immunotherapy can lower systemic toxicities and boost local and systemic immune responses. Several studies have proven the feasibility, repeatability, and safety of this approach, with some promising results in clinical trials. The clinical benefit might be improved in patients with a low tumor burden. Future clinical trials should focus on adequate timing of treatment delivery during the course of the disease, particularly in the neoadjuvant setting.

Corticosteroid treatment for refractory intracranial hypertension: a rescue therapy in patients with severe traumatic brain injury with contusional lesions-a feedback.

INTRODUCTION: Refractory intracranial hypertension (rICH) is a severe complication among patients with severe traumatic brain injury (sTBI). Medical treatment may be insufficient, and in some cases, the only viable treatment option is decompressive hemicraniectomy. The assessment of a corticosteroid therapy against vasogenic edema secondary to severe brain injuries seems interesting to prevent this surgery in sTBI patients with rICH caused by contusional areas. METHODS: This is a monocentric retrospective observational study including all consecutive sTBI patients with contusion injuries and a rICH requiring cerebrospinal fluid drainage with external ventricular drainage between November 2013 and January 2018. Patient inclusion criterium was a therapeutic index load (TIL; an indirect measure of TBI severity) > 7. Intracranial pressure (ICP) and TIL were assessed before and 48 h after corticosteroid therapy (CTC). Then, we divided the population into two groups according to the evolution of the TIL: responders and non-responders to corticosteroid therapy. RESULTS: During the study period, 512 patients were hospitalized for sTBI, and among them, 44 (8.6%) with rICH were included. They received 240 mg per day [120 mg, 240 mg] of Solu-Medrol for 2 days [1; 3], 3 days after the sTBI. The average ICP in patients with rICH before the CTC bolus was 21 mmHg [19; 23]. After the CTC bolus, the ICP fell significantly to less than 15 mmHg (p < 0.0001) for at least 7 days. The TIL decreased significantly the day after the CTC bolus and until day 2. Among these 44 patients, 68% were included in the responder group (n = 30). DISCUSSION: Short and systemic corticosteroid therapy in patients with refractory intracranial hypertension secondary to severe traumatic brain injury seems to be a potentially useful and efficient treatment for lowering intracranial pressure and decreasing the need for more invasive surgeries.

The PEARL Approach for CT-guided Lung Biopsy: Assessment of Complication Rate.

Background Percutaneous CT-guided biopsy of lung nodules is an established method with high diagnostic accuracy but a high rate of pneumothorax and chest tube insertion compared with endobronchial methods. Purpose To investigate the effect of a protocol combining patient positioning biopsy-side down, needle removal during expiration, autologous blood patch sealing, rapid rollover, and pleural patching (PEARL) on complication rate after percutaneous CT-guided lung biopsy, especially chest tube insertion. Materials and Methods In a secondary analysis of both prospectively and retrospectively acquired data from December 2019 to November 2020, consecutive participants underwent biopsy with use of the PEARL protocol (prospective data) and were compared with patients who underwent biopsy at the same tertiary cancer center according to the standard method without any additional techniques (controls, retrospective data). Patient demographics, lesion characteristics, intraprocedural data, complications, and histologic results were recorded and compared. Results One hundred patients in the control group (mean age ± standard deviation, 63 years ± 12; 61 men) and 100 participants in the PEARL group (mean age, 64 years ± 12; 48 men) were evaluated. No differences were found in patient and lesion characteristics. The emphysema rate was 47 of 100 patients (47%) in both groups. The rate of pneumothorax was 37 of 100 patients (37%) in the control group versus 16 of 100 (16%) in the PEARL group (P = .001). Of the pneumothoraxes that occurred, fewer were during the intervention in the PEARL group, with 21 of 37 onsets (57%) in the control group versus three of 16 onsets (19%) in the PEARL group (P < .001). A chest tube was inserted in 13 of 100 patients (13%) in the control group and only in one of 100 (1%) in the PEARL group (P = .002). Histologic findings were diagnostic in 94 of 100 patients (94%) in the control group and 95 of 100 (95%) in the PEARL group (P > .99). Conclusion During CT-guided percutaneous lung biopsy, a protocol of positioning biopsy-side down, needle removal during expiration, autologous blood patch sealing, rapid rollover, and pleural patching, or PEARL, reduced rates of pneumothorax and chest tube insertion. © RSNA, 2021.

Extraction of cement leakages and malpositioned spindles complicating percutaneous interventions: why, when and how?

OBJECTIVES: Cement leakages in soft tissues are a common occurrence during cementoplasty. They may cause chronic pain, and thus treatment failure. Spindle malposition during reinforced cementoplasty may cause vascular, nerve or cartilage injury. Our goal was to evaluate the rate of cement leakage/spindle extraction and describe the techniques used. METHODS: This retrospective monocentre study included 104 patients who underwent reinforced cementoplasty and 3425 patients who underwent cementoplasty between 2012 and 2020. Operative reports and fluoroscopic images were reviewed to identify extraction attempts and their outcomes. RESULTS: Six patients (5.8%) had a malpositioned spindle, and all of them underwent spindle extraction during reinforced cementoplasty, with an 80% success rate. A total of 7 attempts were performed, using 2 different techniques. One thousand one hundred thirty patients (32%) had a cement leak in soft tissues, and 7 (0.6%) underwent cement leakage extraction during cementoplasty, with a 100% success rate. A total of 10 attempts were performed, using 3 different techniques. No major complication related to the extraction procedures occurred. CONCLUSIONS: Spindle malpositions and soft tissue cement leakages are not uncommon. We described 5 different percutaneous techniques that were safe and effective to extract spindles and paravertebral cement fragments. KEY POINTS: • Soft tissue cement leakages or spindle malpositions are a non-rare occurrence during cementoplasty, and may cause technical failure and/or chronic pain. • Most soft tissue cement fragments and malpositioned spindles can easily be extracted using simple percutaneous techniques.

Robotic-assisted CT-guided percutaneous thermal ablation of abdominal tumors: An analysis of 41 patients.

PURPOSE: Robotic assistance is rapidly evolving and may help physicians optimize needle guidance during percutaneous interventions. The purpose of the study was to report feasibility, safety, accuracy, immediate clinical success and short-term local tumor control after robotic-assisted computed tomography (CT)-guided thermal ablation of abdominal tumors. MATERIALS AND METHODS: Forty-one patients who underwent percutaneous thermal ablation of abdominal tumors using robotic-assisted CT-guided were included. All ablations were performed with robotic assistance, using an optically-monitored robotic system with a needle guide sent to preplanned trajectories defined on three-dimensional-volumetric CT acquisitions with respiration monitoring. Endpoints were technical success, safety, distance from needle tip to planned trajectory and number of needle adjustments, and complete ablation rate. RESULTS: Forty-one patients (31 men; mean age, 66.7 ± 9.9 [standard deviation (SD)] years [age range: 41-84 years]) were treated for 48 abdominal tumors, with 79 planned needles. Lesions treated were located in the liver (23/41; 56%), kidney (14/41;34%), adrenal gland (3/41; 7%) or retroperitoneum (1/41; 2%). Technical success was achieved in 39/41 (95%) patients, and 76/79 (96%) needle insertions. The mean lateral distance between the needle tip and planned trajectory was 3.2 ± 4.5 (SD) mm (range: 0-20 mm) before adjustments, and the mean three-dimensional distance was 1.6 ± 2.6 (SD) mm (range: 0-13 mm) after 29 manual depth adjustments (29/78; 37%) and 33 lateral adjustments (33/78; 42%). Two (2/79; 3%) needles required complete manual reinsertion. One grade 3 complication was reported in one patient (1/41; 2%). The overall clinical success rate was 100%. The 3-month local tumor control rate (progression free survival) was 95% (38/41). CONCLUSION: These results provide further evidence on the use of robotic-assisted needle insertion regarding feasibility, safety, and accuracy, resulting in effective percutaneous thermal ablation of abdominal tumors.

Preoperative Spinal Arterial Supply Mapping Using Non-Selective Cone Beam Computed Tomography before Complex Aortic Repair.

Pre-op spinal arterial mapping is crucial for complex aortic repair. This study explores the utility of non-selective cone beam computed tomography (CBCT) for pre-operative spinal arterial mapping to identify the Adamkiewicz artery (AKA) in patients undergoing open or endovascular repair of the descending thoracic or thoracoabdominal aorta at risk of spinal cord ischemia. Pre-operative non-selective dual-phase CBCT after intra-aortic contrast injection was performed in the aortic segment to be treated. The origin of detected AKA was assessed based on image fusion between CBCT and pre-interventional computed tomography angiography. Then, the CBCT findings were compared with the incidence of postoperative spinal cord ischemia (SCI). Among 21 included patients (median age: 68 years, 20 men), AKA was detected in 67% within the explored field of view, predominantly from T7 to L1 intercostal and lumbar arteries. SCI occurred in 14%, but none when AKA was not detected (p < 0.01). Non-selective CBCT for AKA mapping is deemed safe and feasible, with potential predictive value for post-surgical spinal cord ischemia risk. The study concludes that non-selective aortic CBCT is a safe and feasible method for spinal arterial mapping, providing promising insights into predicting post-surgical SCI risk.

Thermal Ablation Combined with Immune Checkpoint Blockers: A 10-Year Monocentric Experience.

PURPOSE: We report a 10-year experience in cancer therapy with concomitant treatment of percutaneous thermal ablation (PTA) and immune checkpoint blockers (ICBs). MATERIAL AND METHODS: This retrospective cohort study included all patients at a single tertiary cancer center who had received ICBs at most 90 days before, or 30 days after, PTA. Feasibility and safety were assessed as the primary outcomes. The procedure-related complications and immune-related adverse events (irAEs) were categorized according to the Common Terminology Criteria for Adverse Events v5.0 (CTCAE). Efficacy was evaluated based on overall survival (OS), progression-free survival (PFS), and local progression-free survival (LPFS) according to the indication, ablation modality, neoplasm histology, and ICB type. RESULTS: Between 2010 and 2021, 78 patients (57% male; median age: 61 years) were included. The PTA modality was predominantly cryoablation (CA) (61%), followed by radiofrequency ablation (RFA) (31%). PTA indications were the treatment of oligo-persistence (29%), oligo-progression (14%), and palliation of symptomatic lesions or prevention of skeletal-related events (SREs) (56%). Most patients received anti-PD1 ICB monotherapy with pembrolizumab (n = 35) or nivolumab (n = 24). The feasibility was excellent, with all combined treatment performed and completed as planned. Ten patients (13%) experienced procedure-related complications (90% grade 1-2), and 34 patients (44%) experienced an irAE (86% grade 1-2). The only factor statistically associated with better OS and PFS was the ablation indication, favoring oligo-persistence (p = 0.02). Tumor response was suggestive of an abscopal effect in four patients (5%). CONCLUSIONS: The concomitant treatment of PTA and ICBs within 2-4 weeks is feasible and safe for both palliative and local control indications. Overall, PTA outcomes were found to be similar to standards for patients not on ICB therapy. While a consistently reproducible abscopal effect remains elusive, the safety profile of concomitant therapy provides the framework for continued assessment as ICB therapies evolve.

Mechanical thrombectomy in basilar artery occlusions: impact of first-line strategy as a function of the occlusion level.

BACKGROUND: Retrospective studies suggest the superiority of first-line contact aspiration (CA) thrombectomy over stent-retriever (SR) in basilar artery occlusions (BAO). We aimed to investigate the impact of first-line mechanical thrombectomy per the occlusion level, considering differences in stroke etiology prevalence between proximal and distal BAO. METHODS: A retrospective, multicentric analysis of the Endovascular Treatment in Ischemic Stroke Registry (ETIS) included consecutive BAO patients treated from January 2016 to May 2022. Patients were categorized into SR (±aspiration) and CA alone groups. Occlusion levels were determined through digital subtraction angiography. Favorable clinical outcome was defined as 90-day modified Rankin Scale (mRS) 0-3. RESULTS: A total of 380 patients were analyzed (251 CA alone, 129 SR±aspiration). Globally, first-line SR showed lower recanalization rates (89.1% vs 94.8%, OR=0.29, 95% CI 0.16 to 0.53; p<0.001) and worse clinical outcomes (mRS 0-3: 46.0% vs 52.2%, OR=0.62, 95% CI 0.44 to 0.87; p=0.006) compared with CA. In proximal occlusions, SR was significantly associated with poorer clinical outcomes (mRS 0-3: 20.9% vs 37.1%; OR=0.40, 95% CI 0.19 to 0.83; p=0.014) despite similar recanalization rates. Conversely, in distal occlusions there was no difference in clinical outcomes although recanalization rates were higher with CA (modified Thrombolysis in Cerebral Infarction score (mTICI 2b/3): 97.7% vs 91.7%; OR=0.17, 95% CI 0.05 to 0.66; p=0.01). CONCLUSIONS: In our BAO population, CA demonstrated better angiographic outcomes in middle and distal occlusions and better clinical outcomes in proximal occlusions. This translated into better angiographic and clinical results in the global study population. Clinical results were particularly influenced by the negative impact of SR on 90-day mRS, independently of recanalization rates in proximal BAO.

The percutaneous management of pulmonary metastases.

Local treatment of lung metastases has been in the front scene since late 90s when an international registry of thoracic surgery reported a median overall survival of 35 months in resected patients versus 15 months in non-resected patients. Today, other local therapies are available for patients with oligometastatic lung disease, including image guided thermal ablation, such as ablation, microwave ablation, and cryoablation. Image-guided ablation is increasingly offered, and now recommended in guidelines as option to surgery. Today, the size of the target tumour remains the main driver of success and selection of patients with limited tumour size allowing for local tumour control in the range of 90% in most recent and larger series targeting lung metastases up to 3.5 cm. Overall survival exceeding five-years in large series of thermal ablation for lung metastases from colorectal origin are align with outcome of same patients treated with surgical resection. Moreover, thermal ablation in such population allows for one-year chemotherapy holidays in all comers and over 18 months in lung only metastatic patients, allowing for improved patient quality of life and preserving further lines of systemic treatment when needed. Tolerance of thermal ablation is excellent and better than surgery with no lost in respiratory function, allowing for repeated treatment when needed. In the future, it is likely that practice of lung surgery for small oligometastatic lung disease will decrease, and that minimally invasive techniques will replace surgery in such indications. Randomized study will be difficult to obtain as demonstrated by discontinuation of many studies testing the hypothesis of surgery versus observation, or surgery versus SBRT.

Percutaneous alcohol embolization and vertebroplasty of a T2 aggressive vertebral hemangioma with prior embolization of dangerous arterial anastomoses.

Aggressive vertebral hemangiomas usually exhibit extraosseous expansion that can result in spinal cord or radicular compression.1 In symptomatic cases, treatment by alcohol embolization and percutaneous vertebroplasty has been reported as feasible, safe, and effective with long-term benefits on neurological symptoms.2 Safety rules before vertebral alcohol embolization include preoperative spinal cord vascularization mapping and opacification through bone needles to assess the absence of dangerous intratumoral anastomoses.In video 1 we present a case of a symptomatic T2 aggressive vertebral hemangioma with dangerous anastomoses between the lesion and both supreme intercostal arteries (SIAs). Embolization by the arterial route of both SIAs was performed, which required good anatomic knowledge of the spinal cord vascularization at the cervicothoracic junction3 4 as a cervical radiculomedullary artery arose from the left costocervical trunk which also fed the left SIA. After occlusion of all dangerous arterial anastomoses, we were able to successfully perform T2 alcohol embolization and percutaneous vertebroplasty. neurintsurg;15/7/728/V1F1V1Video 1Case presentation.

Safety and Efficacy of Percutaneous Liver Microwave Ablation Using a Fully Water-Cooled Choke Ring Antenna: First Multicenter Clinical Report.

INTRODUCTION: The safety and efficacy of a microwave ablation (MWA) system for the liver with novel technologies in field control, antenna cooling through the inner part of the choke ring, and dual temperature monitoring were evaluated in this multicenter retrospective study. MATERIAL AND METHODS: Ablation characteristics and efficacy were assessed on follow-up imaging (computed tomography or magnetic resonance imaging). Safety was evaluated according to CTCAE classification. RESULTS: Eighty-seven liver tumors (65 metastases and 22 hepatocellular carcinomas) measuring 17.8 ± 7.9 mm were treated in 68 patients. Ablation zones measured 35.6 ± 11 mm in longest diameter. The coefficients of variation of the longest and shortest ablation diameters were 30.1% and 26.4%, respectively. The mean sphericity index of the ablation zone was 0.78 ± 0.14. Seventy-one ablations (82%) had a sphericity index above 0.66. At 1 month, all tumors demonstrated complete ablation with margins of 0-5 mm, 5-10 mm, and greater than 10 mm achieved in 22%, 46%, and 31% of tumors, respectively. After a median follow-up of 10 months, local tumor control was achieved in 84.7% of treated tumors after a single ablation and in 86% after one patient received a second ablation. One grade 3 complication (stress ulcer) occurred, but was unrelated to the procedure. Ablation zone size and geometry in this clinical study were in accordance with previously reported in vivo preclinical findings. CONCLUSION: Promising results were reported for this MWA device. The high spherical index, reproducibility, and predictability of the resulting treatment zones translated to a high percentage of adequate safety margins, providing good local control rate.

Electrochemotherapy in radiotherapy-resistant epidural spinal cord compression in metastatic cancer patients.

OBJECTIVE: To report efficacy and safety of percutaneous electrochemotherapy (ECT) in patients with radiotherapy-resistant metastatic epidural spinal cord compression (MESCC). MATERIAL/ METHODS: This retrospective study analyzed all consecutive patients treated with bleomycin-based ECT between February-2020 and September-2022 in a single tertiary referral cancer center. Changes in pain were evaluated with the Numerical Rating Score (NRS), in neurological deficit with the Neurological Deficit Scale, and changes in epidural spinal cord compression were evaluated with the epidural spinal cord compression scale (ESCCS) using an MRI. RESULTS: Forty consecutive solid tumour patients with previously radiated MESCC and no effective systemic treatment options were eligible. With a median follow-up of 5.1 months [1-19.1], toxicities were temporary acute radicular pain (25%), prolonged radicular hypoesthesia (10%), and paraplegia (7.5%). At 1 month, pain was significantly improved over baseline (median NRS: 1.0 [0-8] versus 7.0 [1.0-10], P < .001) and neurological benefits were considered as marked (28%), moderate (28%), stable (38%), or worse (8%). Three-month follow-up (21 patients) confirmed improved over baseline (median NRS: 2.0 [0-8] versus 6.0 [1.0-10], P < .001) and neurological benefits were considered as marked (38%), moderate (19%), stable (33.5%), and worse (9.5%). One-month post-treatment MRI (35 patients) demonstrated complete response in 46% of patients by ESCCS, partial response in 31%, stable disease in 23%, and no patients with progressive disease. Three-month post-treatment MRI (21 patients) demonstrated complete response in 28.5%, partial response in 38%, stable disease in 24%, and progressive disease in 9.5%. CONCLUSIONS: This study provides the first evidence that ECT can rescue radiotherapy-resistant MESCC.

Alkylating Agent-Induced High Tumor Mutational Burden in Medullary Thyroid Cancer and Response to Immune Checkpoint Inhibitors: Two Case Reports.

Background: Patients with metastatic medullary thyroid cancer (MTC) who progressed under tyrosine kinase inhibitors can benefit from an alkylating agent such as dacarbazine or temozolomide. Patient Findings: We describe two patients with metastatic MTC who developed a hypermutant phenotype after alkylating agent treatment. This phenotype was characterized by a high tumor mutational burden (TMB) and a mutational signature indicative of alkylating agent mutagenesis (single-base substitution 11). Both patients received immune checkpoint inhibitors, with partial morphological responses, clinical benefit, and progression-free survival of 6 and 9 months, respectively. Summary and Conclusions: Based on the described observations, we suggest that a hypermutant phenotype may be induced after alkylating agent treatment for MTC and the sequential use of immunotherapy should be further explored as a treatment option for MTC patients with increased TMB.

Local and distant response to intratumoral immunotherapy assessed by immunoPET in mice.

BACKGROUND: Despite the promising efficacy of immune checkpoint blockers (ICB), tumor resistance and immune-related adverse events hinder their success in cancer treatment. To address these challenges, intratumoral delivery of immunotherapies has emerged as a potential solution, aiming to mitigate side effects through reduced systemic exposure while increasing effectiveness by enhancing local bioavailability. However, a comprehensive understanding of the local and systemic distribution of ICBs following intratumoral administration, as well as their impact on distant tumors, remains crucial for optimizing their therapeutic potential.To comprehensively investigate the distribution patterns following the intratumoral and intravenous administration of radiolabeled anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and to assess its corresponding efficacy in both injected and non-injected tumors, we conducted an immunoPET imaging study. METHODS: CT26 and MC38 syngeneic colorectal tumor cells were implanted subcutaneously on both flanks of Balb/c and C57Bl/6 mice, respectively. Hamster anti-mouse CTLA-4 antibody (9H10) labeled with zirconium-89 ([89Zr]9H10) was intratumorally or intravenously administered. Whole-body distribution of the antibody was monitored by immunoPET imaging (n=12 CT26 Balb/c mice, n=10 MC38 C57Bl/6 mice). Tumorous responses to injected doses (1-10 mg/kg) were correlated with specific uptake of [89Zr]9H10 (n=24). Impacts on the tumor microenvironment were assessed by immunofluorescence and flow cytometry. RESULTS: Half of the dose was cleared into the blood 1 hour after intratumoral administration. Despite this, 7 days post-injection, 6-8% of the dose remained in the intratumoral-injected tumors. CT26 tumors with prolonged ICB exposure demonstrated complete responses. Seven days post-injection, the contralateral non-injected tumor uptake of the ICB was comparable to the one achieved through intravenous administration (7.5±1.7% ID.cm-3 and 7.6±2.1% ID.cm-3, respectively) at the same dose in the CT26 model. This observation was confirmed in the MC38 model. Consistent intratumoral pharmacodynamic effects were observed in both intratumoral and intravenous treatment groups, as evidenced by a notable increase in CD8+T cells within the CT26 tumors following treatment. CONCLUSIONS: ImmunoPET-derived pharmacokinetics supports intratumoral injection of ICBs to decrease systemic exposure while maintaining efficacy compared with intravenous. Intratumoral-ICBs lead to high local drug exposure while maintaining significant therapeutic exposure in non-injected tumors. This immunoPET approach is applicable for clinical practice to support evidence-based drug development.

Imaging and histological features of tumor biopsy sample predict aggressive intrasegmental recurrence of hepatocellular carcinoma after radiofrequency ablation.

Aggressive intrasegmental recurrence (AIR) is a form of local recurrence associated with a dismal prognosis and defined by multiple nodules or by an infiltrative mass with a tumor thrombus, occurring in the treated segment, after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). We aimed to identify radiological and/or histological characteristics of tumor biopsy predictive of AIR. We retrospectively analyzed patients treated by No-Touch multi-bipolar RFA (mbpRFA) for a first HCC with a systematic per-procedural tumor biopsy positive for diagnosis of HCC. The first recurrence was classified as non-aggressive local recurrence, AIR or intrahepatic distant recurrence. 212 patients were included (168 men; mean age 67.1 years; mean tumor size 28.6 mm, 181 cirrhosis). AIR occurred in 21/212 patients (10%) and was associated with a higher risk of death (57% in patients with AIR vs 30% without AIR, p = 0.0001). Non-smooth tumor margins, observed in 21% of the patients and macro-trabecular massive histological subtype, observed in 12% of the patients were independently related to a higher risk of AIR (HR: 3.7[1.57;9.06], p = 0.002 and HR:3.8[2.47;10], p = 0.005 respectively). Non smooth margins at imaging and macro-trabecular massive histological subtype are associated with AIR and could be considered as aggressive features useful to stratify therapeutic strategy.

Synergizing liver systemic treatments with interventional oncology: friend or foe?

Interventional radiology techniques provide excellent local tumor control for small tumors in various organs, but several limitations can hamper the oncological outcomes such as the tumor size or the number of lesions. Technical improvements, optimal patient selection and combination with systemic therapies, including immune checkpoint inhibitors, have been successfully developed to overcome these barriers.In this setting, chemotherapy and targeted therapies aim to diminish the tumor burden in addition to local treatments, while immunotherapies may have a synergistic effect in terms of mechanism of action on the tumor cell as well as the immune environment, with multiple treatment combinations being available. Finally, interventional Rrdiology treatments often increase tumor antigen exposure to the immune system, and thus stimulate a specific antitumor immune response that can act beyond the treated site. Notwithstanding their many benefits, combination treatment may also result in complications, the most feared may be auto-immune-related adverse events.In early studies, several combined therapies have shown promising levels of safety and efficacy, particularly in hepatocellular carcinoma.This review provides a comprehensive and up-to-date overview of results of combined therapies for primary and secondary liver malignancies. Recent advances and future perspectives will be discussed.