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PURPOSE: To assess immunogenic effects in unembolized contralateral tumor after single lobar yttrium-90 transarterial radioembolization (90Y-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 90Y-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: 90Y-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 90Y-TARE and checkpoint inhibition in MSS CRLM warrant further investigation.
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BACKGROUND: To study hippocampus subfield volumes in patients after microsurgical clipping (MC) and/or endovascular coiling (EC) of intracranial aneurysms. METHODS: Hippocampus subfield volumetry was performed using FreeSurfer v6.0 in 51 patients (35 females, mean age 54.9 ± 11.9 years, range 24-78 years). Visual inspection of image and segmentation quality was performed prior to statistical analyses. Multiple regression analysis, controlled for age, sex, and side of treatment, was used to assess the impact of prior MC and history of subarachnoid haemorrhage (SAH) on hippocampus subfield volumes (cornu ammonis (CA)-2/3, CA-4, subiculum). Partial correlation analyses were used to assess effect of multiple treatments on hippocampus subfield volumes. RESULTS: Prior MC was significantly associated with lower hippocampal subfield volumes in MC patients for right and left CA-2/3 (ß = -22.32 [-40.18, -4.45]; p = 0.016 and ß = -20.03 [-39.38, -0.68]; p = 0.043) and right CA-4 (ß = -17.00 [-33.86, 0.12]; p = 0.048). History of SAH was not significantly associated with hippocampal subfield volumes. We observed a higher disease burden in the MC cohort. The number of aneurysms correlated with right-sided hippocampal subfield volumes while the number of treatment interventions did not. CONCLUSION: In this explorative study, we found that history of MC was significantly associated with lower volumes in distinct hippocampal subfields, which may be a consequence of a more extensive treatment. This could indicate specific atrophy of CA-2/3 after MC and should motivate hippocampal subfield assessment in larger cohorts.