Background & Aims Tremelimumab is a fully human monoclonal antibody that binds to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on the surface of activated T lymphocytes. Ablative therapies induce a peripheral immune response which may enhance the effect of anti-CTLA4 treatment in patients with advanced hepatocellular carcinoma (HCC). This study aimed to demonstrate whether tremelimumab could be combined safely and feasibly with ablation. Methods Thirty-two patients with HCC were enrolled: male:female: 28:4; median age: 62 (range 36–76). Patients were given tremelimumab at two dose levels (3.5 and 10 mg/kg i.v.) every 4 weeks for 6 doses, followed by 3-monthly infusions until off-treatment criteria were met. On day 36, patients underwent subtotal radiofrequency ablation or chemoablation. Staging was performed by contrast-enhanced CT or MRI scan every 8 weeks. Results No dose-limiting toxicities were encountered. The most common toxicity was pruritus. Of the 19 evaluable patients, five (26.3%; 95% CI: 9.1–51.2%) achieved a confirmed partial response. Twelve of 14 patients with quantifiable HCV experienced a marked reduction in viral load. Six-week tumor biopsies showed a clear increase in CD8+ T cells in patients showing a clinical benefit only. Six and 12-month probabilities of tumor progression free survival for this refractory HCC population were 57.1% and 33.1% respectively, with median time to tumor progression of 7.4 months (95% CI 4.7 to 19.4 months). Median overall survival was 12.3 months (95% CI 9.3 to 15.4 months). Conclusions Tremelimumab in combination with tumor ablation is a potential new treatment for patients with advanced HCC, and leads to the accumulation of intratumoral CD8+ T cells. Positive clinical activity was seen, with a possible surrogate reduction in HCV viral load. Lay summary Studies have shown that the killing of tumors by direct methods (known as ablation) can result in the immune system being activated or switched on. The immune system could potentially also recognize and kill the cancer that is left behind. There are new drugs available known as immune checkpoint inhibitors which could enhance this effect. Here, we test one of these drugs (tremelimumab) together with ablation.

Personalized therapies play an increasingly critical role in cancer care; Image guidance with multimodality image fusion facilitates the targeting of specific tissue for tissue characterization, and plays a role in drug discovery and optimization of tailored therapies. PET, MRI and contrast enhanced CT may offer additional information not otherwise available to the operator during minimally invasive image guided procedures such as biopsy and ablation. With use of multimodality image fusion for image-guided interventions, navigation with advanced modalities does not require the physical presence of the PET, MRI, or CT imaging system. Several commercially available methods of image fusion and device navigation are reviewed along with an explanation of common tracking hardware and software. An overview of current clinical applications for multimodality navigation is provided.

Navigation systems, devices and intra-procedural software are changing the way we practice interventional oncology. Prior to the development of precision navigation tools integrated with imaging systems, thermal ablation of hard-to-image lesions was highly dependent upon operator experience, spatial skills, and estimation of positron emission tomography-avid or arterial-phase targets. Numerous navigation systems for ablation bring the opportunity for standardization and accuracy that extends our ability to use imaging feedback during procedures. Existing systems and techniques are reviewed, and specific clinical applications for ablation are discussed to better define how these novel technologies address specific clinical needs, and fit into clinical practice.