Minimally Invasive Therapies for Hepatocellular Carcinoma: Mechanisms of Local Control and Systemic Immunologic Response

Minimally invasive treatments for hepatocellular carcinoma (HCC) are a cornerstone in the management of this challenging disease. For many years, percutaneously guided ablative techniques, such as radiofrequency ablation (RFA), cryoablation, and microwave ablation (MWA), have successfully treated many different solid malignancies including HCC. Since the initial implementation of these ablative techniques, there have been many advances in the design, technique, and patient selection as well as investigation into the body’s response to treatment. The mechanisms of thermal-based ablative techniques, advantages and disadvantages of each technique, subsequent immunologic response following ablation, and advances in care that utilize combination therapy to potentiate the immunologic response creating a robust and long-term immunity to HCC are outlined in this chapter

A case report: Retrograde arterial embolization of locally-injected SpaceOAR hydrogel material into the right common iliac artery bifurcation

Biodegradable hydrogel-based matrices are becoming more widely utilized for a variety of medical applications, including SpaceOAR which is a hydrogel injected into the recto-prostatic space under ultrasound guidance to protect the rectum during prostate radiation therapy. Although a greater number of these procedures are being performed, there are no case reports on the potential complications which may result. In this report, we present the first case of retrograde embolization of SpaceOAR hydrogel into the right common iliac artery during routine office administration, as well as subsequent interventional angiography, inpatient and outpatient management, and clinical and imaging results at 1.5-month patient follow-up

Temporary Reversal of Hepatoenteric Collaterals during ⁹⁰Y Radioembolization Planning and Administration

Purpose: This paper aims to evaluate the safety and efficacy of the temporary redirection of blood flow of hepatoenteric collaterals using a balloon catheter in the common hepatic artery (CHA) to prevent the nontarget deposition of 90Y microspheres. Materials and Methods: In this retrospective single-center study of patients who received 90Y radioembolization (RE) from September 2010 to September 2015, diagnostic (67 patients) or treatment (72 patients) angiograms with the attempted use of a balloon catheter in the CHA to temporarily direct blood flow away from the hepatoenteric arteries were analyzed. SPECT/CT nuclear scintigraphy was performed after both diagnosis and treatment. Results: Overall, only 12 hepatoenteric arteries in 11 patients required embolization due to persistent hepatoenteric flow despite the use of the balloon occlusion technique in a total of 86 patients. Physicians performed the 90Y RE using balloon occlusion with glass (n = 22) or resin (n = 50) microspheres. Over 80% administration of the prescribed 90Y dose was accomplished in 34 (67%) resin and 20 (95%) glass microsphere patients. Post-treatment 90Y RE scintigraphy confirmed the absence of extrahepatic activity in all patients. One grade 2 gastrointestinal ulcer was present after 90 days of follow-up. Conclusion: Temporary CHA occlusion with a balloon catheter is a reliable and reproducible alternative to the conventional coil embolization of hepatoenteric arteries during diagnostic Tc-99m macroaggregated albumin and therapeutic 90Y RE delivery

1534 Clinical activity of SD-101 with immune checkpoint inhibition (ICI) in metastatic uveal melanoma liver metastasis (MUM-LM) from the PERIO-01 Phase 1 trial

BackgroundMUM-LM are resistant to ICIs for several reasons including the prevalence of myeloid-derived suppressor cells (MDSCs). PFS has been limited, even with approved therapies such as tebentafusp (median 3.3 months) with grade 3/4 AE rates typically >30%. TLR9 agonists are capable of MDSC polarization but drug delivery has historically been limited using an intra-tumoral approach. Pressure-enabled drug delivery (PEDDTM) of SD-101, a TLR9 agonist, has the potential to overcome these barriers to improve outcomes.MethodsPERIO-01 is a phase 1 trial of hepatic arterial SD-101 via PEDD in MUM-LM (NCT04935229), with dose-escalation cohorts as monotherapy (Cohort A), with nivolumab (Cohort B), or nivolumab + ipilimumab (Cohort C). SD-101 is delivered over 2 outpatient cycles, with 3 weekly doses/cycle.Results53 patients received at least one dose of SD-101: 13 in Cohort A, 25 in Cohort B, and 15 in Cohort C. Median age was 65 and 45% were female. 70% received prior MUM-LM treatment, and 8 (15%) received tebentafusp. Fifteen participants (28%) had LM >5cm and 18 (44%) had >10 LMs. One patient experienced partial response (Cohort B 4 mg) that is ongoing at 258 days. Six additional patients had decreases in target lesion size (SD), 3 ongoing at a median follow-up of 168 days. Across dose levels, median PFS was highest in Cohort B (2 mg) at 11.7 months, and disease control rate of 86% (6/7 SD). Serious grade 3/4 treatment-related AEs (TRAEs) to SD-101 or ICI were documented in 8% of subjects: 0% in Cohort A, 4% in Cohort B, and 20% in Cohort C, with an overall Grade 3/4 TRAE rate of 21%. PEDD of SD-101 resulted in reductions in LM monocytic MDSC (mMDSC) by immunofluorescence, along with decreased expression of ARG1, CD163, and FASN. We also observed evidence of immune activation in LM with increased CD4+ and CD8+ T cells, decreased Treg, and increased IFNg and IFNa2 gene expression. These were associated with evidence of systemic immune activation peripherally characterized by increased proliferating CD8+ T and NK cells, and increased IP-10, TNFa, IFNg, IL-2R, and IL-18. Among 25 patients with evaluable ctDNA data, 68% had a decrease relative to peak, with complete clearance in 28%.ConclusionsDelivery of SD-101 by PEDD plus systemic ICI in MUM-LM patients results in clinical activity with median PFS of 11.7 months, MDSC re-programming, and evidence of peripheral and intra-tumoral immune activation. Phase 2 of PERIO-01 is planned for expansion of the optimal dose.Trial RegistrationNCT04935229Ethics ApprovalThe study was IRB approved at all sites and participants signed written informed consen