Purpose: Tilsotolimod is an investigational synthetic Toll-like receptor 9 (TLR9) agonist that has demonstrated antitumor activity in preclinical models. The ILLUMINATE-101 phase I study explored the safety, dose, efficacy, and immune effects of intratumoral (it) tilsotolimod monotherapy in multiple solid tumors. Patients and Methods: Patients with a diagnosis of refractory cancer not amenable to curative therapies received tilsotolimod in doses escalating from 8 to 32 mg into a single lesion at weeks 1, 2, 3, 5, 8, and 11. Additional patients with advanced malignant melanoma were enrolled into an expansion cohort at the 8 mg dose. Objectives included characterizing the safety, establishing the dose, efficacy, and immunologic assessment. Blood samples and tumor biopsies of injected and noninjected lesions were obtained at baseline and 24 hours after treatment for immune analyses. Results: Thirty-eight and 16 patients were enrolled into the dose escalation and melanoma expansion cohorts, respectively. Deep visceral injections were conducted in 91% of patients. No dose-limiting toxicities (DLT) or grade 4 treatment-related adverse events were observed. Biopsies 24 hours after treatment demonstrated an increased IFN pathway signature and dendritic cell maturation. Immunologic profiling revealed upregulation of IFN-signaling genes and modulation of genes for checkpoint proteins. In the dose escalation cohort, 12 (34%) of 35 evaluable patients achieved a best overall response rate (ORR) of stable disease (SD), whereas 3 (19%) of 16 evaluable patients in the melanoma cohort achieved stable disease. Conclusions: Overall, tilsotolimod monotherapy was generally well tolerated and induced rapid, robust alterations in the tumor microenvironment. See related commentary by Punekar and Weber, p. 5007

Desmoid tumors are locally aggressive soft tissue tumors with variable clinical presentation. As is the case with most relatively rare tumors, a multidisciplinary team approach is required to best manage these patients. Surgical resection, systemic therapy, and radiation therapy have classically been mainstays of treatment for desmoid tumors; however, a more conservative “wait-and-see” approach has been adopted given their high recurrence rates and significant morbidity associated with the aforementioned therapies. Given the challenges of classical treatment methods, interventional radiologists have begun to play a significant role in minimally invasive interventions for desmoid tumors. Herein, the authors review imaging characteristics of desmoid tumors, current management recommendations, and minimally invasive therapeutic intervention options.

Over the last several decades, a number of new treatment options for patients with hepatocellular carcinoma (HCC) have been developed. While treatment decisions for some patients remain clear cut, a large numbers of patients have multiple treatment options, and it can be hard for multidisciplinary teams to come to unanimous decisions on which treatment strategy or sequence of treatments is best. This article reviews the available data with regard to two treatment strategies, immunotherapies and locoregional therapies, with a focus on the potential of locoregional therapies to be combined with checkpoint inhibitors to improve outcomes in patients with locally advanced HCC. In this review, the available data on the immunomodulatory effects of locoregional therapies is discussed along with available clinical data on outcomes when the two strategies are combined.

Surgical resection remains the cornerstone of curative treatment for intrahepatic cholangiocarcinoma (iCCA), but this option is only available to a small percentage of patients. For patients with unresectable iCCA, systemic therapy with gemcitabine and platinum-based agents represents the mainstay of treatment; however, the armamentarium has grown to include targeted molecular therapies (e.g., FGFR2 inhibitors), use of adjuvant therapy, liver transplantation in select cases, immunotherapy, and locoregional liver-directed therapies. Despite advances, iCCA remains a challenge due to the advanced stage of many patients at diagnosis. Furthermore, given the improving options for systemic therapy and the fact that the majority of iCCA patients succumb to disease progression in the liver, the role of locoregional therapies has increased. This review will focus on the expanding role of interventional radiology and liver-directed therapies in the treatment of iCCA.