BACKGROUND:The relationship between the radiographic portal vein-superior mesenteric vein (PV-SMV) involvement and pathological PV-SMV (pPV) invasion has been established in upfront surgery cases of pancreatic cancer (PC); however, evidence remains limited for patients receiving neoadjuvant therapy (NAT). This study aimed to evaluate the association of radiographic findings with pPV invasion in patients treated with NAT, and to examine whether this association differs between patients treated with neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACRT). METHODS:We retrospectively analyzed patients with PC whose tumors contacted the PV-SMV on radiographic imaging before or after NAT. The relationship between radiographic findings and pPV invasion was evaluated in subgroups defined by pre- and post-NAT imaging findings. RESULTS:Tumor size, PV-SMV contact length, and contact angle were significantly reduced in post-NAT imaging. Radiographic PV-SMV involvement showed limited association with pPV invasion in the entire cohort. The overall pPV invasion rate was 15% and did not differ between the NAC and NACRT groups (17% vs. 13%, p = 0.790). Among patients with a pre-NAT tumor size of < 20 mm, the pPV invasion rate was significantly lower in the NACRT group than in the NAC group (29% vs. 0%, p = 0.007). This difference was not observed in patients with a pre-NAT tumor size ≥ 20 mm (12% vs. 19%, p = 0.438). Across other radiographic classifications, pPV invasion rates remained comparable between treatment groups. CONCLUSIONS:The association of radiographic findings with pPV invasion differs between patients treated with NAC and NACRT in patients with small tumors.

BACKGROUND:First-line chemotherapy with maintenance therapy is expected to be well-tolerated and improve survival in patients with metastatic colorectal cancer (mCRC). This study evaluated the efficacy and safety of trifluridine/tipiracil (TAS-102) plus bevacizumab (Bev) as maintenance therapy for mCRC, omitting both oxaliplatin and fluoropyrimidines. MATERIALS AND METHODS:Patients with untreated mCRC initially received induction chemotherapy with fluoropyrimidine, oxaliplatin plus bevacizumab for 3-4 months. After achieving stable disease or better on imaging, 52 patients transitioned to maintenance therapy with TAS+Bev: TAS-102 (35 mg/m2, twice daily on days 1-5 and 8-12) plus Bev (5.0 mg/kg on Days 1 and 15, intravenously). Progression-free survival 1 (PFS1), defined as the time from the start of maintenance therapy to disease progression or death, was evaluated as the primary endpoint. RESULTS:The median cumulative dose of oxaliplatin during induction was 529 mg/m2. Median PFS1 during TAS+Bev maintenance was 8.7 months (95% CI: 5.5-12.3). The response rate and disease control rate during maintenance were 59.6% and 94.2%, respectively. Oxaliplatin reintroduction was feasible in 53.8% (28/52) of patient with a median total first-line chemotherapy duration was 16.2 months (95% CI: 14.5-20.6). Safety outcomes, including dose intensity and adverse events, were acceptable. CONCLUSION:This strategy of switching to first-line maintenance therapy with TAS+Bev demonstrated promising efficacy and safety. This strategy effectively avoided cumulative neurotoxicity, preserved quality of life and enabled reintroduction of oxaliplatin, suggesting it may represent a promising alternative strategy for patients ineligible for prolonged oxaliplatin-based treatment. Overall survival analysis is currently ongoing. [UMIN Trial ID: UMIN000031317].

Although a low skeletal muscle mass index (SMI) leads to poor overall survival (OS) after gastrectomy in patients with gastric cancer, the cutoff value that predicts long-term survival in patients with normal SMI remains unclear. This study aimed to determine the cutoff SMI value for predicting OS in patients with normal SMI. This multicenter retrospective cohort study included patients with normal SMI who underwent radical gastrectomy for pStage I–III primary gastric cancer between January 2011 and December 2016. The patients were randomly divided at a 6:4 ratio into a training set, which examined the cutoff values for SMI, and a validation set, which validated the cutoff values. Patients were classified into high and low SMI groups according to the cutoff values. We compared OS between the high- and low-SMI groups using log-rank test and identified prognostic factors using Cox proportional hazards regression analysis. Of the 2516 patients, 1389 (55.2

Nivolumab has become a standard treatment for advanced or recurrent esophageal squamous cell carcinoma (ESCC). However, reliable blood-based biomarkers predictive of response remain undefined. We investigated dynamic changes in peripheral PD-1+ CD8+ T-cell subsets during nivolumab therapy and evaluated their clinical significance. Fifty-seven patients with advanced or recurrent ESCC treated with nivolumab were enrolled in this retrospective observational study. Peripheral blood mononuclear cells were collected before treatment and at 1, 2, and 4 weeks after initiation. Flow cytometric analyses evaluated the expression of CD103, CD45RA, Tim-3, LAG-3, TIGIT, and Ki-67 among nivolumab-binding PD-1+ CD8+ T cells. Associations between immunophenotypic changes, treatment response, survival outcomes, immune-related adverse events (irAEs), and nutritional/inflammatory indices were analyzed. The objective response rate was 24.6

ABSTRACT KDM5B, a member of the KDM5 family of histone demethylases, plays a critical role in transcriptional repression by demethylating H3K4me2/3. It regulates key biological processes such as development, stem cell maintenance, and oncogenesis, and its aberrant expression is implicated in various cancers. Accordingly, KDM5B is considered a promising therapeutic target in cancer drug discovery. In this study, we performed a screening to identify novel inhibitors of KDM5B. Through this screening, we identified a common core scaffold associated with KDM5B inhibitory activity, and subsequent optimization of the side‐chain structures led to the identification of a series of compounds with IC50 values ranging from several nanomolar to several micromolar. Evaluation of growth inhibitory activity using the JFCR39 human cancer cell line panel revealed that the final lead compounds, JB‐157 and JB‐161, exhibited GI50 values in the low micromolar range. In a xenograft model, where the human colorectal cancer cell line HT‐29 was implanted into NOD/SCID mice, administration of these compounds resulted in antitumour effects, with JB‐161 showing particularly pronounced tumor suppression in a subset of treated animals. Furthermore, combination treatment with in vivo CAR‐T cell therapy and JB‐161 in C57BL/6J mice was associated with alterations in chromatin accessibility in tumor and immune cell populations. Taken together, these results suggest that JB‐161 is a candidate KDM5B inhibitor associated with chromatin accessibility changes and antitumour activity.

Abstract Fucosylated haptoglobin (Fuc-Hp) has been recognized as a cancer-associated glycoform. We previously established a monoclonal antibody, 10-7G mAb, which detects both Fuc-Hp and its precursor prohaptoglobin (proHp). Recent studies have suggested that proHp itself may serve as a cancer-associated biomarker with clinical implications distinct from those of Fuc-Hp. Importantly, proHp is produced during inflammation and cancer progression and may exert biological activities different from mature haptoglobin (Hp). These observations highlight the need for a reagent that can specifically detect proHp. However, to date, no antibody strictly specific to proHp has been available. In this study, we generated a monoclonal antibody, 21-4F mAb, which specifically recognizes human proHp without cross-reactivity to mature Hp. Using 21-4F mAb, we developed a proHp-specific enzyme-linked immunosorbent assay and integrated it with assays for several types of Hp, enabling independent quantification of three Hp-related isoforms. Serum analyses of healthy volunteers and patients with chronic pancreatitis or pancreatic cancer revealed distinct alterations among these isoforms, and their combined use provided the highest diagnostic performance. Taken together, 21-4F mAb offers a novel analytical tool for investigating the pathophysiological significance of proHp and may contribute to the development of refined biomarker panels for cancer diagnosis and disease monitoring.

BACKGROUND Appendectomy reduces the occurrence and controls the severity of ulcerative colitis (UC); however, how it exerts these effects remains unclear. AIM To elucidate the contribution of appendix-associated immune responses in intestinal inflammation and their relevance to the effects of appendectomy in UC. METHODS This study was conducted at Graduate School of Medicine, The University of Osaka. We included patients undergoing surgery for UC and those without inflammatory bowel disease undergoing colorectal cancer surgery as controls. Appendiceal tissues were collected from both patient groups, and macroscopically normal appendices located at least 10 cm from the tumor were used as controls. Single-cell RNA sequencing, immunohistochemistry, and flow cytometry were performed. RESULTS Single-cell RNA sequencing identified T, B, plasma, innate lymphoid, and mast cells, together with other myeloid cells in appendiceal tissues. A hallmark feature of the appendices in UC was an increase in immunoglobulin G (IgG)-expressing plasma cells. Immunohistochemistry revealed significantly reduced IgG levels in the large intestines of patients with UC who had undergone an appendectomy compared with levels in those who did not undergo appendectomy. Repertoire analysis revealed an increased production of IgG antibodies bearing an integrin-binding motif at antigen-recognition sites in patients with UC. CONCLUSION The appendix is a major site of pathogenic IgG antibody production in patients with UC, providing the immunological basis for appendectomy as a treatment for UC.

ABSTRACT Objectives Microsatellite instability‐high (MSI‐H) or mismatch repair‐deficient (dMMR) colorectal cancer (CRC) is a distinct subtype. Although immune checkpoint inhibitors are used for advanced cases, data on its frequency and characteristics, especially in resectable Asian CRC, remain limited. This study investigated MSI‐H/dMMR frequency and features in Japanese patients to support future personalized treatment strategies. Methods This multicenter observational study included 1464 patients with pathologically confirmed primary CRC enrolled from April 2024 to March 2025 at 25 institutions affiliated with Osaka University. MSI/MMR status and clinicopathological data were extracted from a prospectively maintained database. Univariate analyses were performed to evaluate factors associated with MSI‐H/dMMR. Results Among 1464 patients, 137 (9.4%) had MSI‐H/dMMR tumors. MSI/MMR testing was conducted preoperatively in 772 patients (52.7%). MSI‐H/dMMR was more frequent in patients aged ≥ 70 years, in females (OR = 1.46, p = 0.036), and in tumors located in the cecum, ascending, or transverse colon ( p < 0.001). It was significantly less common in Stage IV disease (OR = 0.22, p < 0.001) and KRAS ‐mutant tumors (OR = 0.22, p < 0.001), but strongly associated with BRAF V600E mutation (OR = 52.41, p < 0.001), poorly differentiated adenocarcinoma (OR = 7.17, p < 0.001), and mucinous adenocarcinoma (OR = 3.10, p = 0.002). Conclusions MSI‐H/dMMR CRC accounted for 9.4% of Japanese patients, including resectable cases, and exhibited distinct clinical and molecular characteristics. These findings provide a basis for future personalized treatment strategies in this population.

Combination immune checkpoint inhibition with ipilimumab plus nivolumab (NIVO + IPI) has shown promising efficacy in advanced esophageal squamous cell carcinoma (ESCC) in the CheckMate648 trial. However, real-world evidence regarding its safety, efficacy as first-line therapy, and host-related biomarkers relevant to immunotherapy remains limited. This multicenter retrospective study evaluated a large cohort of 111 patients with unresectable advanced or recurrent ESCC who received first-line NIVO + IPI therapy. Treatment response, treatment-related adverse events, and prognostic factors were analyzed. The objective response and disease control rates in cases with target lesions were 44.0

Neoadjuvant gemcitabine plus S-1 (GS) followed by surgery and adjuvant S-1 is the standard of care for resectable pancreatic cancer. Since ~73% of newly diagnosed pancreatic cancer patients are aged ≥70, effective treatments are strongly needed in this geriatric population. In unresectable pancreatic cancer, gemcitabine plus nab-paclitaxel (GnP) is widely used, even among geriatric patients. To evaluate the survival advantage of neoadjuvant GnP over GS for geriatric patients with resectable pancreatic cancer, an open-label randomized phase III trial (JCOG2101C) has been initiated since October 2022. A total of 400 patients will be enrolled from 28 institutions within 3 years. The primary endpoint is overall survival. This trial was registered at the Japan Registry of Clinical Trials as jRCTs031220351 [https://jrct.mhlw.go.jp/latest-detail/jRCTs031220351].

Abstract Background: Detecting circulating tumor cells (CTCs) as a peripheral blood liquid biopsy is a promising approach. We previously succeeded in visualizing viable-CTCs (v-CTCs) with high biological activity from the peripheral blood of resectable and borderline resectable pancreatic cancer (PC) patients using a novel telomerase-specific oncolytic virus (TelomeScan F35). This study aimed to analyze the clinical significance of v-CTC detection and the expression of PD-L1 on v-CTCs in PC patients to explore potential therapeutic selection strategies. Methods: Thirty-nine PC patients were analyzed. CTCs were analyzed at pre-/post-operative time points in the Upfront Surgery (S) group, and at pre-NACRT, post-NACRT, and post-operative time points in the Neoadjuvant Chemoradiotherapy (NACRT) group (RT + GEM + S-1). PD-L1 expression was also assessed in v-CTCs, primary tumors and metastatic lymphnodes. Results: [S Group] (n=24; M/F=12/12; median age 73). All patients underwent curative resection. Six patients were consistently v-CTC negative (pre- and post-op); five of these patients remained disease-free, with only one case of peritoneal recurrence. In contrast, 18 patients were v-CTC positive at either or both time points; 13 of these developed early distant metastatic recurrence post-surgery. [NACRT Group] (n=15; M/F=4/11; median age 67). All patients underwent curative resection. Five patients were consistently v-CTC negative at all three time points and all remain disease-free. In six patients who were v-CTC positive pre-NACRT, the v-CTC count significantly increased post-NACRT in five cases, and three of them developed early liver metastasis, suggesting that RT might induce v-CTC intravasation/dissemination. [PD-L1 Expression] PD-L1 analysis was performed on 18 patients in the S group and 3 in the NACRT group. In primary tumors of the S group, PD-L1 expression was observed in 0%/10%/20%/40% of tumor cells in 6/6/4/2 cases, respectively. The expression rate on v-CTCs was 97% pre-operation and 81% post-operation. Among 12 patients with lymph node metastasis, PD-L1 expression was positive in only 4 cases (33%). In the NACRT group, primary tumors were all PD-L1 negative. The expression rate on v-CTCs was 50% pre-NACRT, 96% post-NACRT, and 50% post-operation. Two cases showed lymph node metastasis, both PD-L1 negative. Conclusion: The presence of v-CTC dissemination suggests a risk of metastasis development following NACRT, advocating for upfront surgery or neoadjuvant chemotherapy (NAC) without RT in v-CTC positive patients. Given the high rate of PD-L1 expression on v-CTCs, immune checkpoint inhibitors are expected to be effective for targeting v-CTCs and controlling distant metastasis. Detection of v-CTC dissemination may be utilized for therapeutic selection in PC patients. Citation Format: Masahiro Tanemura, Hisataka Ogawa, Yoshiaki Ohmura, Tadafumi Asaoka, Yasuo Urata, Daisaku Yamada, Hirofumi Akita, Hidetoshi Eguchi. Clinical significance of viable circulating tumor cells (v-CTCs) and PD-L1 expression in pancreatic cancer patients using a novel oncolytic virus system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1069.