Hepatic and Overall Progression-Free Survival After Percutaneous Hepatic Perfusion (PHP) as First-Line or Second-Line Therapy for Metastatic Uveal Melanoma.

BACKGROUND: Uveal melanoma often metastasizes to the liver, portending a poor prognosis. Melphalan/hepatic delivery system (HDS) via percutaneous hepatic perfusion (PHP) is a minimally invasive means of circulating high-dose chemotherapy through the affected liver. This study evaluated melphalan/HDS use as either first-line or second-line treatment to guide treatment sequencing. PATIENTS AND METHODS: A retrospective review included patients with hepatic-dominant metastatic uveal melanoma who underwent melphalan/HDS treatment via PHP from 2008 to 2023. RESULTS: A total of 30 patients were identified; 53.3% female, with a median age of 63.5 years (37-78 years). Median follow-up time was 14.5 months. First-line therapies included melphalan/HDS (n = 17), liver-directed (n = 7), and immunotherapy (n = 6). Second-line therapies included melphalan/HDS (n = 6), immunotherapy (n = 5), and liver-directed (n = 3). Median hepatic progression-free survival (hPFS) for first-line melphalan/HDS, immunotherapy, and liver-directed therapy was 17.6/8.8/9.2 months, respectively (P = 0.002). Median hPFS for second-line melphalan/HDS, immunotherapy, and liver-directed therapy was not reached/14.7/7.5 months, respectively (P < 0.001). Median overall PFS for first-line melphalan/HDS, immunotherapy, and liver-directed therapy was 15.4/8.8/9.2 months, respectively (P = 0.04). Median overall PFS for second-line melphalan/HDS, immunotherapy, and liver-directed therapy was 22.2/14.7/7.5 months, respectively (P = 0.001). CONCLUSIONS: Melphalan/HDS via PHP for metastatic uveal melanoma to the liver was found to have significantly improved hPFS and overall PFS when used as first-line therapy compared with immunotherapy or liver-directed therapy. PHP continued to demonstrate improved hPFS and PFS when used as second-line therapy compared with second-line immunotherapy or liver-directed therapy.

Angiosomal radiopathologic analysis of transarterial radioembolization for the treatment of hepatocellular carcinoma.

PURPOSE: To assess the radiopathologic correlation following Yttrium-90 transarterial radioembolization (TARE) of hepatocellular carcinoma (HCC) using variable radiodosimetry to identify imaging surrogates of histologic response. METHODS: Twelve patients with HCC underwent ablative (≥ 190 Gy) and/or non-ablative (< 190 Gy) TARE delivered in a segmental, lobar, or combined fashion as a surgical neoadjuvant or bridge to transplantation. Both targeted tumor and treatment angiosome were analyzed before and after TARE utilizing hepatocyte-specific contrast-enhanced MRI or contrast-enhanced CT. Responses were graded using EASL and mRECIST criteria. Histologic findings including percent tumor necrosis and adjacent hepatic substrate effects were correlated with imaging features. RESULTS: Complete pathologic necrosis (CPN) was observed in 7/12 tumors post-TARE. Ablative and non-ablative dosing resulted in CPN in 5/6 and 2/6 tumors, respectively. Hyperintensity on T2-weighted imaging, the absence of hepatocyte-specific gadolinium contrast uptake, and plateau or persistent enhancement kinetics in the angiosome correlated with CPN and performed similarly to EASL and mRECIST criteria in predicting CPN. CONCLUSIONS: The absence of hepatocyte-specific contrast uptake, increased signal on T2-weighted sequences, and plateau or persistent enhancement in the angiosome may represent MRI surrogates of CPN following TARE of HCC. These findings correlated with EASL and mRECIST response criteria. Further investigation is needed to determine the role of these findings as possible adjuncts to conventional imaging criteria.

HLA-DRB1-associated rheumatoid arthritis risk at multiple levels in African Americans: hierarchical classification systems, amino acid positions, and residues.

OBJECTIVE: To evaluate HLA-DRB1 genetic risk of rheumatoid arthritis (RA) in African Americans by 3 validated allele classification systems and by amino acid position and residue, and to compare genetic risk between African American and European ancestries. METHODS: Four-digit HLA-DRB1 genotyping was performed on 561 autoantibody-positive African American cases and 776 African American controls. Association analysis was performed on Tezenas du Montcel (TdM), de Vries (DV), and Mattey classification system alleles and separately by amino acid position and individual residues. RESULTS: TdM S2 and S3P alleles were associated with RA (odds ratio [95% confidence interval] 2.8 [2.0-3.9] and 2.1 [1.7-2.7], respectively). The DV (P = 3.2 × 10(-12)) and Mattey (P = 6.5 × 10(-13)) system alleles were both protective in African Americans. Amino acid position 11 (permutation P < 0.00001) accounted for nearly all variability explained by HLA-DRB1, although conditional analysis demonstrated that position 57 was also significant (0.01 ≤ permutation P ≤ 0.05). The valine and aspartic acid residues at position 11 conferred the highest risk of RA in African Americans. CONCLUSION: With some exceptions, the genetic risk conferred by HLA-DRB1 in African Americans is similar to that in individuals of European ancestry at multiple levels: classification system (e.g., TdM), amino acid position (e.g., 11), and residue (Val11). Unlike that reported for individuals of European ancestry, amino acid position 57 was associated with RA in African Americans, but positions 71 and 74 were not. Asp11 (odds ratio 1 in European ancestry) corresponds to the 4-digit classical allele *09:01, which is also a risk allele for RA in Koreans.