Shizuoka Cancer Center

The author is an editorial board member of Digestive Endoscopy, has received research grants from The Japanese Foundation for Research and Promotion of Endoscopy and The Japanese Gastroenterological Association, has received speaker honorariums from the OLYMPUS Company and the Boston Scientific corporation, and holds an advisory role with the OLYMPUS Company.

683 Background: Enfortumab vedotin (EV) is a standard therapy for metastatic urothelial carcinoma (mUC) after platinum-based chemotherapy and immune checkpoint inhibitors. However, optimal early dosing strategies remain unclear in real-world practice. Maintaining relative dose intensity (RDI) may influence efficacy, yet the prognostic role of early RDI (eRDI) and its relationship with adverse event–related dose modification (AE-DM) are not well defined. Clarifying whether early dose modification affects outcomes is crucial for balancing efficacy and tolerability in EV therapy. Methods: We retrospectively analyzed 119 patients with mUC treated with EV monotherapy at multiple Japanese institutions from 2021 to 2024. Among them, 84 patients who underwent at least one post-baseline radiographic assessment and did not show early progressive disease (PD) were included in the efficacy analysis. Early RDI was defined as the mean RDI during the first three months. AE-DM was defined as any reduction, delay, or interruption due to toxicity. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan–Meier method and compared using the log-rank test, stratified by AE-DM status (positive or negative). Results: In the PD-excluded cohort, patients with eRDI ≥80% had significantly longer PFS and OS than those with eRDI <80% (median PFS: 8.5 vs 4.3 months, p=0.008; OS: not reached vs 11.2 months, p=0.012). Among AE-DM–negative patients, low eRDI predicted worse outcomes (median PFS: 11.7 vs 4.2 months, p=0.001; OS: not reached vs 13.8 months, p=0.021). Conversely, in AE-DM–positive patients, survival did not differ between eRDI groups, suggesting that clinically guided dose modification did not compromise efficacy. Conclusions: Early RDI predicted survival in patients who tolerated standard dosing without AE-DM, whereas dose modification for toxicity preserved efficacy. Maintaining early intensity is important for fit patients, while individualized dose modification may ensure safety and effectiveness in those with AE-DM. eRDI may serve as a practical early indicator in real-world EV therapy. Survival outcomes according to eRDI and AE-DM status. Cohort n Median PFS (months, eRDI ≥80% vs <80%) p-value Median OS (months, eRDI ≥80% vs <80%) p-value All PD-excluded 84 8.5 vs 4.3 0.008 NR vs 11.2 0.012 AE-DM (−) 49 11.7 vs 4.2 0.001 NR vs 13.8 0.021 AE-DM (+) 35 6.3 vs 6.1 0.67 15.1 vs 14.9 0.82 PFS, progression-free survival; OS, overall survival; eRDI, early relative dose intensity; PD, progressive disease; AE-DM, adverse event-related dose modification; NR, not reached.

Colorectal serrated lesions (SLs) are recognized as precursors of colorectal cancer (CRC); however, their detection rates and prevalence remain inadequately defined. We aimed to assess their detection rates and estimate their prevalence in the Asia-Pacific, as well as to examine their associated factors. This was a multicenter prospective study in the Asia-Pacific. Asymptomatic individuals aged 40-74 years undergoing first-time colonoscopy for CRC screening were prospectively enrolled. To ensure precise prevalence estimates, colonoscopy procedures involved repeated proximal colon inspection using pan-chromoendoscopy with indigo carmine dye. Detection rates of proximal SLs and sessile serrated lesions (SSLs) were calculated. Mixed-effects logistic regression analyses, accounting for institution-level variability, were performed to identify factors associated with proximal SL and SSL detection. Associations between SLs and synchronous advanced colorectal neoplasia (ACN) were evaluated. Among 965 participants, detection rates of proximal SLs and SSLs were 16.1% (95% confidence interval [CI], 13.8-18.5) and 8.6% (6.9-10.6), respectively. Institutional differences affected detection of proximal SLs (adjusted median OR, 1.44; 95% CI, 1.25-1.79) and SSLs (1.34; 1.18-1.62). A family history of CRC was associated with higher SSL detection (adjusted odds ratio [OR], 2.36; 95% CI, 1.29-4.33). Detection of proximal SLs was associated with synchronous ACN (OR, 1.94; 95% CI, 1.24-3.02 and 1.90; 1.18-3.07, respectively). This multicenter study demonstrates that detection rates and estimated prevalence of SLs are higher than previously reported in the Asia-Pacific and highlights the impact of institutional differences, challenging the notion of their low regional prevalence. UMIN-CTR number, UMIN 000042890.

Preoperative bilateral drainage for perihilar cholangiocarcinoma via endoscopic ultrasound-guided hepaticogastrostomy using a novel side-hole plastic stent Fig. 1 a The novel plastic stent (ADFlap, Century Medical, Tokyo, Japan) is equipped with double flaps to prevent migration.b The stent has a tapered tip, with a flap located at the distal 4 cm and two side holes, enabling bile drainage through both the tip and side holes. Fig. 2 Computed tomographic (CT) images showed bile duct wall thickening and upstream biliary dilatation, leading to the diagnosis of bismuth type 3a perihilar cholangiocarcinoma.a Axial view.b Coronal view.c Schema based on CT findings.

Lymphovenous anastomosis (LVA) is a microsurgical procedure that redirects stagnant lymph flow into the venous circulation, reducing fluid stasis in patients with secondary limb lymphedema. Although previous studies have reported that complex decongestive therapy redistributes fluid from the affected leg to other body segments, whether fluid reduction after LVA results from systemic elimination or intersegmental redistribution remains unclear. This study aimed to clarify the mechanism by analyzing the changes in segmental body water (SBW) volume using bioelectrical impedance analysis (BIA).We retrospectively analyzed the data of 40 Japanese women with unilateral stage II secondary leg lymphedema who underwent LVA from 2013 to 2021. Multifrequency segmental BIA was used to assess extracellular water, intracellular water, and SBW in the legs, trunk, and arms. Measurements were performed preoperatively and at least 12 months postoperatively. Changes in segmental and total body water (TBW) were statistically evaluated.Significant reductions were observed in SBW in the affected leg, and in the TBW (affected leg: 5.80-5.20 L, p < 0.001; TBW: 25.6-25.0 L, p = 0.002), with no significant changes in the unaffected leg, trunk, or arms. Extracellular and intracellular water in the affected leg decreased significantly (p = 0.001 and p < 0.001, respectively), whereas the percentage of extracellular water remained stable.LVA achieved sustained reductions in segmental and TBW volumes, localized to the affected leg, without compensatory increases in other body segments. These findings support the efficacy of leg LVA in achieving long-term fluid homeostasis through systemic elimination of excess lymphatic fluid rather than redistribution.

Abstract Background: The DESTINY-Breast04 (DB-04) trial established trastuzumab deruxtecan (T-DXd) as the standard of care for patients (pts) with the metastatic breast cancer (mBC) newly classified as HER2-low status (HER2 IHC 1+, or 2+/ISH−). However, in the DB-04 trial, the number of pts with hormone receptor-negative (HR−)/HER2-low mBC was limited, and pts with stable brain metastases (BMs) were included, while those with active BMs were excluded. The HALLOW study (UMIN000051259) is a large-scale ongoing prospective observational study conducted in Japan with the aim of providing effectiveness and safety data for T-DXd in these clinically important populations, which were underrepresented in the DB-04 trial. Here, we report the interim analysis results for pts with BMs. Methods: The HALLOW study enrolled, from June 2023, approximately 600 pts diagnosed with HER2-low mBC (HR+/−, with/without BMs, including active BMs) who had previously received chemotherapy and were scheduled to receive T-DXd treatment. This interim analysis included pts diagnosed with BMs (current or past) by local investigators. For the effectiveness analysis, only those with BMs confirmed by Brain-independent central review (ICR) based on brain MRI and/or CT images were included. Active BMs were defined as cases where no local treatment was performed on the brain lesion or where there was regrowth or symptom worsening after local treatment. Effectiveness outcomes included intracranial progression-free survival (IC-PFS) and intracranial objective response rate (IC-ORR) assessed by Brain-ICR according to RECIST version 1.1, while progression-free survival (PFS) and overall survival (OS) were assessed by investigators. For the safety analysis, pts who had received T-DXd at least once were included. Safety outcomes include incidence of treatment-emergent adverse events (TEAEs) graded by CTCAE, including ≥ grade (Gr) 3 TEAEs, ≥ Gr1 interstitial lung disease (ILD), and ≥ Gr1 TEAEs that led to discontinuation of T-DXd treatment. Follow-up plan will continue until July 2026. Results: At the data cutoff date of August 31, 2024, 42 pts had physician-diagnosed BMs, of whom 33 were Brain-ICR confirmed and met the criteria for active BMs. In this set, the median age was 55 (range: 42-79) years; the median prior line of chemotherapy in the metastatic setting was 2 (range: 0-7); HER2 status at each local site was IHC 2+/ISH− in 7 pts (21%) and IHC 1+ in 26 pts (79%); 25 pts (76%) were HR+, 8 pts (24%) were HR−. 5 pts (15%) had Brain-ICR-confirmed leptomeningeal disease. At a median follow-up period of 4.1 months (mo) (range: 1.4-12.6), the median IC-PFS was 8.0 mo (95% confidence interval [CI]: 3.9-not estimated), and the 6-mo IC-PFS rate was 57.6% (95% CI: 30.7-77.4) until the data cutoff date. A total of 22 pts was eligible for proper tumor evaluation during the follow-up period by Brain-ICR. Among the 22 pts who could be properly evaluated, the IC-ORR was 9.1% (complete response n=0, partial response n=2; 95% CI: 1.1-29.2). The median PFS was 6.7 mo (95% CI: 4.0-11.1), with a 6-mo PFS rate of 59.0% (95% CI: 34.9-76.7). The median OS was not reached, and the 6-mo survival rate was 77.1% (95% CI: 51.5-90.3). In the safety analysis set (n=42; median follow-up period: 4.1 mo [range: 0.4-12.6]), ≥ Gr3 TEAEs and ≥ Gr3 TEAEs related to T-DXd treatment occurred in 18 (43%) and 11 (26%) pts, respectively. ≥ Gr1 ILD occurred in 2 pts (5%), 1 (2%) of whom experienced Gr 5 ILD, and ≥ Gr1 TEAEs that led to T-DXd discontinuation occurred in 3 pts (7%), with two of these being ILD and the other seizure. Conclusions: While longer follow-up and additional data are needed to confirm these findings, the current data provide tentative support for the effectiveness and safety of T-DXd in this BMs population including active BMs, which was not included in the DB-04 trial. Citation Format: N. Niikura, T. Yamanaka, Y. Aoyama, A. Kataoka, T. Toyama, S. Sakai, M. Endo, K. Kaneko, H. Iwata, T. Yamashita, J. Tsurutani, R. Horii, Y. Kikawa, Y. Hirakawa, S. Yamazaki, W. Hashimoto, E. Tokuda, S. Saji. Interim analysis results for the effectiveness and safety of trastuzumab deruxtecan in patients with HER2-low breast cancer and brain metastases: The HALLOW study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD13-11.

Background Radical surgery with free-flap reconstruction for advanced head and neck squamous cell carcinoma (HNSCC) carries a high risk of postoperative complications. Aims/Objectives To identify the complication most strongly associated with poor oncologic outcomes. Materials and Methods We retrospectively evaluated 346 patients who underwent free-flap reconstruction between January 2013 and December 2022. Postoperative complications were classified using Clavien–Dindo (CD) grading. Overall survival (OS), recurrence-free survival (RFS), hospital stay, and the surgery-to-postoperative radiotherapy (S-PORT) interval were evaluated. Results Surgical site infection (SSI) was the most common complication (n = 56). Patients with CD grade ≥ IIIa SSI showed significantly worse 5-year OS (hazard ratio [HR], 3.075; 95% confidence interval [CI], 1.605–5.892; p < 0.001) and RFS (HR, 2.095; 95% CI, 1.135–3.866; p = 0.018). Multivariate analysis confirmed CD grade ≥ IIIa SSI as an independent prognostic factor for OS (HR, 3.539; 95% CI, 1.786–7.012; p < 0.001) and RFS (HR, 2.095; 95% CI, 1.155–4.053; p = 0.016). These patients had significantly longer hospital stays, whereas S-PORT intervals showed no difference. Conclusions and Significance CD grade ≥ IIIa SSI independently predicts poor survival after free-flap reconstruction in HNSCC. Preventing and promptly managing SSIs are crucial to improving long-term outcomes.