https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/203 2026-04-09T01:43:10Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/64311 Title: Artificial intelligence-powered spatial analysis of tumor-infiltrating lymphocytes as a predictive biomarker for axitinib in adenoid cystic carcinoma Authors: Kim, Dong Hyun; Lim, Yoojoo; Ock, Chan-Young; Park, Gahee; Park, Seonwook; Song, Heon; Ma, Minuk; Mostafavi, Mohammad; Kang, Eun Joo; Ahn, Myung-Ju; Lee, Keun-Wook; Kwon, Jung Hye; Yang, Yaewon; Choi, Yoon Hee; Kim, Min Kyoung; Ji, Jun Ho; Yun, Tak; Kim, Sung-Bae; Keam, Bhumsuk Abstract: Background: This study analyzed the predictive value of artificial intelligence (AI)-powered tumor-infiltrating lymphocyte (TIL) analysis in recurrent or metastatic (R/M) adenoid cystic carcinoma (ACC) treated with axitinib.Methods: Patients from a multicenter, prospective phase II trial evaluating axitinib efficacy in R/M ACC were included in this study. H&E whole-side images of archival tumor tissues were analyzed by Lunit SCOPE IO, an AI-powered spatial TIL analyzer.Results: Twenty-seven patients were included in the analysis. The best response was stable disease, and the median progression-free survival (PFS) was 11.1 months (95% CI, 9.2-13.7 months). Median TIL densities in the cancer and surrounding stroma were 25.8/mm(2) (IQR, 8.3-73.0) and 180.4/mm(2) (IQR, 69.6-342.8), respectively. Patients with stromal TIL density >342.5/mm(2) exhibited longer PFS (p = 0.012).Conclusions: Cancer and stromal area TIL infiltration were generally low in R/M ACC. Higher stromal TIL infiltration was associated with a longer PFS with axitinib treatment. 2023-12-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/64412 Title: Clinical activity of nivolumab in combination with eribulin in HER2-negative metastatic breast cancer: A phase IB/II study (KCSG BR18-16) Authors: Kim, Se Hyun; Im, Seock-Ah; Suh, Koung Jin; Lee, Kyung-Hun; Kim, Min Hwan; Sohn, Joohyuk; Park, Yeon Hee; Kim, Ji-Yeon; Jeong, Jae Ho; Lee, Kyoung Eun; Choi, In Sil; Park, Kyong Hwa; Kim, Hee-Jun; Cho, Eun Kyung; Park, So Yeon; Kim, Milim; Kim, Jee Hyun Abstract: Aim: We evaluated the efficacy and safety of nivolumab and eribulin combination therapy for metastatic breast cancer (BC) in Asian populations.Methods: In this parallel phase II study, adult patients with histologically confirmed recurrent/metastatic hormone receptor-positive/HER2-negative (HR+HER2-) or triple-negative BC (TNBC) were prospectively enroled from 10 academic hospitals in Korea (ClinicalTrials.gov Identifier: NCT04061863). They received nivolumab (360 mg) on day 1 plus eribulin (1.4 mg/m2) on days 1 and 8 every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was the investigator-assessed 6-month progression-free survival (PFS) rate in each subtype. Secondary endpoints included investigator-assessed objective response rate (ORR) as per Response Evaluation Criteria in Advanced Solid Tumors version 1.1, disease control rate, overall survival, and treatment toxicity. The association between PD-L1 expression and efficacy was investigated.Results: Forty-five patients with HR+HER2-BC and 45 with TNBC were enroled. Their median age was 51 (range, 31-71) years, and 74 (82.2%) received one or two prior treatments before enrolment. Six-month PFS was 47.2% and 25.1% in the HR+HER2-and TNBC cohorts, respectively. Median PFS was 5.6 (95% confidence interval [CI]: 5.3-7.4) and 3.0 (95% CI: 2.1-5.2) months in the HR+HER2-and TNBC groups, respectively. ORRs were 53.3% (complete response [CR]: 0, partial response [PR]: 24) and 28.9% (CR: 1, PR: 12). Patients with PD-L1+ tumours (PD-L1 expression >= 1%) and PD -L1-tumours (ORR 50% versus 53.8% in HR+HER2-, 30.8% versus 29.0% in TNBC) had similar ORRs. Neutropenia was the most common grade 3/4 adverse event; the most common immune-related adverse events (AEs) were grades 1/2 hypothyroidism and pruritus. Five patients discontinued therapy because of immune-related AEs. 2023-12-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/64270 Title: Management of classical Philadelphia chromosome-negative myeloproliferative neoplasms in Asia: consensus of the Asian Myeloid Working Group Authors: Gill, Harinder; Leung, Garret M. K.; Ooi, Melissa G. M.; Teo, Winnie Z. Y.; Wong, Chieh-Lee; Choi, Chul Won; Wong, Gee-Chuan; Lao, Zhentang; Rojnuckarin, Ponlapat; Castillo, Ma. Rosario Irene D.; Xiao, Zhijian; Hou, Hsin-An; Kuo, Ming-Chung; Shih, Lee-Yung; Gan, Gin-Gin; Lin, Chien-Chin; Chng, Wee-Joo; Kwong, Yok-Lam Abstract: Myeloproliferative neoplasms (MPN) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized clinically by the proliferation of one or more hematopoietic lineage(s). The classical Philadelphia-chromosome (Ph)-negative MPNs include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The Asian Myeloid Working Group (AMWG) comprises representatives from fifteen Asian centers experienced in the management of MPN. This consensus from the AMWG aims to review the current evidence in the risk stratification and treatment of Ph-negative MPN, to identify management gaps for future improvement, and to offer pragmatic approaches for treatment commensurate with different levels of resources, drug availabilities and reimbursement policies in its constituent regions. The management of MPN should be patient-specific and based on accurate diagnostic and prognostic tools. In patients with PV, ET and early/prefibrotic PMF, symptoms and risk stratification will guide the need for early cytoreduction. In younger patients requiring cytoreduction and in those experiencing resistance or intolerance to hydroxyurea, recombinant interferon-alpha preparations (pegylated interferon-alpha 2A or ropeginterferon-alpha 2b) should be considered. In myelofibrosis, continuous risk assessment and symptom burden assessment are essential in guiding treatment selection. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in MF should always be based on accurate risk stratification for disease-risk and post-HSCT outcome. Management of classical Ph-negative MPN entails accurate diagnosis, cytogenetic and molecular evaluation, risk stratification, and treatment strategies that are outcome-oriented (curative, disease modification, improvement of quality-of-life). 2023-12-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/64002 Title: Identification and overcoming rituximab resistance in diffuse large B-cell lymphoma using next-generation sequencing Authors: Jeon, Min Ji; Yu, Eun Sang; Choi, Chul Won; Kim, Dae Sik Abstract: Background/Aims: Although rituximab, an antiCD20 monoclonal antibody, has dramatically improved the clinical out-comes of diffuse large B-cell lymphoma, rituximab resistance remains a challenge.Methods: We developed a rituximab-resistant cell line (RRCL) by sequential exposure to gradually increasing concentrations of rituximab in a rituximab-sensitive cell line (RSCL). When the same dose of rituximab was administered, RRCL showed a smaller decrease in cell viability and apoptosis than RSCL. To determine the differences in gene expression between RSCL and RRCL, we performed next-generation sequencing.Results: In total, 1,879 differentially expressed genes were identified, and in the over-representation analysis of Consensus-PathDB, mitogen-activated protein kinase (MAPK) signaling pathway showed statistical significance. MAPK13, which encodes the p38d protein, was expressed more than four-fold in RRCL. Western blot analysis revealed that phosphop38 expression was increased in RRCL, and when p38 inhibitor was administered, phosphop38 expression was significantly decreased. Therefore, we hypothesized that p38 MAPK activation was associated with rituximab resistance. Previous studies have suggested that p38 is associated with NF-?B activation. Deferasirox has been reported to inhibit NF-?B activity and suppress phosphorylation of the MAPK pathway. Furthermore, it also has cytotoxic effects on various cancers and synergistic effects in overcoming drug resistance. In this study, we confirmed that deferasirox induced dose-dependent cytotoxicity in both RSCL and RRCL, and the combination of deferasirox and rituximab showed a synergistic effect in RRCL at all combination concentrations. Conclusions: We suggest that p38 MAPK, especially p38d, activation is associated with rituximab resistance, and deferasirox may be a candidate to overcome rituximab resistance. 2023-11-01T00:00:00Z