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Purpose: To assess immunogenic effects in unembolized contralateral tumor after single lobar yttrium-90 transarterial radioembolization ( 90 Y-TARE) of colorectal liver metastases (CRLMs)., Material and Methods: The analysis comprised 10 patients with microsatellite stable (MSS) CRLM scheduled for staged treatment in the prospective AROMA trial. Eligibility criteria included bilobar metastatic disease with >5 lesions without any treatment within 3 weeks. Baseline biopsy was followed by initial 90 Y-TARE treatment of 1 liver lobe, followed by a second biopsy of yet untreated tumors in the other liver lobe at a median of 13 days (range, 4-49 days) immediately before second treatment. Tumor biopsies and peripheral blood mononuclear cells (PBMCs) were collected before treatments for immune cell analysis. Patients were stratified into responders and nonresponders based on tumor control or progression during follow-up., Results: At baseline, responders (n = 4) displayed lower concentrations of FoxP3 + cells and colocation of CD4 + FoxP3 + cells than nonresponders (both P = .02) in tumor tissues. At second biopsy, nonresponders showed a higher CD68 + macrophage density (P = .0014) than responders. Responders displayed fewer CD4 + FoxP3 + T cells than CD8 + T cells at all time points (P = .02 and P = .0428). Nonresponders demonstrated a trending increase in CD68 + macrophages (P = .062), as well as a higher CD8 + PD1 + /CD8 + ratio (P = .062). PBMCs of nonresponders displayed lower CD8 + PD1 + T cells and CD8 + PD1 + /CD8 + ratio at both time points., Conclusions: 90 Y-TARE induces local immunogenic effects in nonexposed MSS CRLM, as well as systemic exhaustion of immune cells in nonresponders. Clinical implications such as a prognostic role or synergism of 90 Y-TARE and checkpoint inhibition in MSS CRLM warrant further investigation., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: To perform radiofrequency (RF) ablation of hepatocellular carcinoma (HCC) and to assess serological and histopathological markers of tumorigenesis in distant untreated tumors to determine whether these were associated with unfavorable outcomes such as early relapse and increased biological aggressiveness., Materials and Methods: The study cohort comprised 13 patients from a prospective single-arm study. All patients underwent 2 ablation sessions of multifocal HCC nodules 14 days apart. Core biopsy samples of untreated tumors were acquired at baseline and at the time of the second ablation session. Samples were stained immunohistochemically with Ki-67 (proliferation) and CD34 (microvasculature). Blood plasma was obtained at baseline and 2 days after the initial ablation session and analyzed for hepatocyte growth factor (HGF), vascular endothelial growth factor C, and angiopoietin-2 using an enzyme-linked immunosorbent assay. The clinical follow-up period ranged from 7 to 25 months. Patients were stratified as responders (complete remission or limited and delayed recurrence at >6 months; n = 6) or nonresponders (any recurrence within 6 months or >3 new tumors or any new tumor of >3 cm thereafter; n = 7)., Results: In 3 of 7 nonresponders, the Ki-67 index markedly increased in untreated tumors, whereas Ki-67 was stable in all responders. Microvascular density strongly increased in a single nonresponder only. HGF and angiopoietin-2 increased by >30% in 3 of 7 and 4 of 7 nonresponders, respectively, whereas they were stable or decreased in responders. Overall, ≥2 biomarkers were elevated in 6 of 7 (85.7%) nonresponders, whereas 4 of 6 responders demonstrated no increased biomarker and 2 patients demonstrated increase in 1 biomarker only (P = .002)., Conclusions: RF ablation of HCC can produce protumorigenic factors that induce effects in distant untreated tumors. These may potentially function as biomarkers of clinical outcome., (Copyright © 2023 SIR. Published by Elsevier Inc. All rights reserved.)