Fukuyama City Hospital

Abstract Background: To assess recurrence risk in ER-positive, HER2-negative early breast cancer, multigene assays (MGAs) are useful in addition to clinicopathological factors. In Japan, Curebest™ 95GC was developed in 2011 and introduced clinically in 2013. Oncotype DX® was added to national health insurance in 2023. While adjuvant chemotherapy is often considered for patients classified as high-risk by any MGA, treatment decisions can be complex. Furthermore, breast cancers identified as high-risk by MGAs often exhibit higher pathological complete response (pCR) rates, suggesting increased sensitivity to chemotherapy. This study aimed to evaluate MGAs from two perspectives—prognostic prediction and NAC sensitivity—to inform individualized treatment strategies. Materials and Methods: We analyzed microarray gene expression data from public databases to identify patients with ER-positive, HER2-negative early breast cancer. In this study, Curebest™ 95GC, developed in Japan, was used post-analysis for research purposes only. Based on microarray expression data, we calculated PAM50, 21GC (Oncotype DX® surrogate analyses), EndoPredict (EP), and either 95GC or 155GC. In Study 1(n=555), we assessed the prognostic value of each MGA and evaluated recurrence risk based on the number of high-risk classifications. In study2(n=550), we evaluated the predictive value of each MGA for pCR rate and analyzed the relationship between NAC sensitivity and the combined assessment of the number of high-risk classifications treated with NAC. Results: In Study 1, all four MGAs (PAM50, 21GC, EP, and 95GC) significantly stratified DRFS between high- and low-risk groups (p =8.93e-08, 2.31e-08, 3.64e-07, and 9.25e-10), with comparable prognostic performance. Patients were grouped by the number of high-risk classifications. A 5-year DRFS of 97% was observed in patients with 0 high-risk classifications, compared to 66% in those with 4. Patients were further stratified into two groups: those with 0 or 1 high-risk classification and those with ≥2. The 0-1 group showed a 5-year DRFS of 96.7%, while the ≥2 group had a significantly worse prognosis at 79.0% (p=2.04e-11). The combined assessment provided better prognostic accuracy than any individual MGA alone. Notably, patients with only one high-risk result showed excellent outcomes, suggesting endocrine therapy alone may suffice. Conversely, those deemed low-risk by all MGAs may not require adjuvant chemotherapy.In Study 2, high-risk patients had significantly higher pCR rates across all MGAs. 155GC showed the strongest stratification (p=1.62e-08). Patients classified as high-risk by all four MGAs had significantly higher pCR rates than those with 0-3 high-risk classifications (p=9.37e-11). 95GC provides CEL files containing expression data for all 20,000 genes. This allows concurrent calculation of multiple MGAs, facilitating evaluation and reducing cost. Use of CEL files supports integrated MGA analysis, and may support precise personalized treatment. Conclusion: Combining four MGAs improves prediction over single MGAs. This integrated genomic approach offers a promising strategy to optimize individualized treatment in ER-positive, HER2-negative early breast cancer. Citation Format: M. Nishida, R. Tsunashima, N. Hirotani, S. Kitano, C. Matsui, S. Matsumoto, A. Watanabe, C. Kato, M. Morita, K. Sakaguchi, Y. Naoi. Integrated Prognostic and Chemotherapy Sensitivity Assessment Using Multiple Gene Assays in ER-positive, HER2-negative Early Breast Cancer [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 PS3-08-25.

<title>Abstract</title> Purpose Although image-enhanced endoscopy (IEE) is useful, its benefit over white light imaging (WLI) for the detection of superficial non-ampullary duodenal epithelial tumors (SNADETs) remains unclear. We evaluated whether narrow-band imaging (NBI) and texture and color enhancement imaging (TXI) could improve SNADET visibility compared to WLI under CO ₂ insufflation and underwater conditions. Methods We conducted a post-hoc analysis using a prospectively collected image database from patients with SNADET enrolled in a multicenter observational study. We used the EVIS X1 system with a GIF-H290Z or GIF-EZ1500 endoscope to compare the visibility scores for the recognition of SNADETs. We also measured the color difference (ΔE*), saturation difference (ΔC*), and lightness difference(ΔL*) between the tumor and background mucosa. Results We analyzed 50 lesions, comprising 46 intramucosal adenocarcinomas and 4 adenomas. Under CO ₂ insufflation, TXI provided a significantly higher visibility score than the WLI (2.7 ± 0.8 vs 2.5 ± 0.9, <italic>P</italic> = 0.002); however, no significant differences were observed between TXI and NBI (2.7 ± 0.8 vs 2.6 ± 0.7, <italic>P</italic> = 0.072). Underwater conditions yielded significantly higher visibility scores than CO ₂ insufflation across the three modes (WLI, 3.1 ± 0.6 vs. 2.5 ± 0.9, <italic>P</italic> &lt; 0.001; NBI, 2.9 ± 0.7 vs. 2.6 ± 0.7, <italic>P</italic> &lt; 0.001; TXI, 3.2 ± 0.5 vs. 2.7 ± 0.8, <italic>P</italic> &lt; 0.001). The ΔC* in TXI was significantly higher than that in WLI under CO ₂ insufflation (8.5 ± 6.0 vs 5.9 ± 3.9, <italic>P</italic> &lt; 0.001) and underwater condition (9.2 ± 5.6 vs 6.6 ± 3.5, <italic>P</italic> &lt; 0.001). Conclusion TXI significantly improved SNADET visibility compared to WLI under CO ₂ insufflation and underwater conditions, likely due to the increased saturation difference.

To evaluate whether regional treatment settings are associated with differences in the clinical outcomes among older gastric cancer patients undergoing curative gastrectomy. This multicenter retrospective study included 327 patients aged ≥ 80 years who underwent curative gastrectomy for gastric cancer. The patients were classified into urban (n = 118) and rural (n = 209) groups. The baseline characteristics, surgical outcomes, and long-term outcomes were compared. Patients in rural areas had poorer performance statuses, more comorbidities, worse nutritional and inflammatory profiles, and longer distances to the hospital. However, no differences were observed between the urban and rural groups in terms of the surgical approach, postoperative complication rates, or the administration of adjuvant chemotherapy. The 5-year overall survival rates in the rural and urban groups were 66.6% and 59.8%, respectively (p = 0.197). A multivariate Cox regression analysis identified Eastern Cooperative Oncology Group performance status ≥ 2 (hazard ratio: 2.02), carcinoembryonic antigen ≥ 5 ng/mL (hazard ratio: 1.92), pathological stage III (hazard ratio: 3.72), and Clavien-Dindo grade ≥ III complications (hazard ratio: 2.51) as independent predictors of overall survival. The comparable surgical and long-term survival outcomes between patients treated in rural and urban areas suggest that equitable surgical care may be achievable across different geographic settings.

Background: No reports have been identified comparing the treatment outcomes of tympanoplasty using autologous tissue and fibrin glue with those of tympanic membrane regeneration therapy based on basic fibroblast growth factor. Aims/Objectives To compare the surgical outcomes in relation to tympanic membrane regeneration therapy and myringoplasty for tympanic membrane perforation. Material and methods The present study comprised a total of 23 ears of tympanic membrane regeneration therapy and 8 ears of myringoplasty, as performed at our hospital between January 2022 and December 2024. Gender, age, anesthetic method, operative time, tympanic membrane perforation closure rate, and postoperative hearing improvement in ears with perforation closure were compared between the two groups. Furthermore, in the regenerative therapy group, postoperative satisfaction was subjectively assessed using the Visual Analog Scale (VAS). Results In comparison with tympanoplasty, tympanic membrane regeneration therapy demonstrated a statistically significant reduction in operative time. However, no other statistically significant differences were observed. The VAS results indicate an average hearing improvement of 62.7, and an average overall satisfaction with the surgery of 77.5. Conclusions and significance Regenerative therapy has the potential to become a new treatment option because it is less invasive than myringoplasty.

An 86-year-old woman with a history of hepatocellular carcinoma was brought to our emergency department after an indoor fall. Her chief complaint was pain in the left thigh and chest. The patient was diagnosed with a pathological femoral shaft fracture, bone metastasis, and acute myocardial infarction. She underwent preoperative embolization and percutaneous coronary intervention, followed by internal fixation on the same day as the injury. The patient was discharged without postoperative myocardial infarction and was able to walk independently using a walker. Femoral diaphyseal fractures and coronary events require urgent intervention, and their coexistence makes it particularly difficult to determine the treatment sequence and timing. In addition, if the fracture is pathological due to bone metastasis, management becomes even more challenging. A multidisciplinary team is essential for the successful management of such complex cases.

Background/Objectives: Prolonged use of denosumab in patients with metastatic breast cancer has raised concerns about the development of medication-related osteonecrosis of the jaw (MRONJ). However, the threshold at which the risk increases remains unclear. Methods: This retrospective cohort study analyzed patients with breast cancer and bone metastases who received denosumab between May 2012 and August 2024. Associations between cumulative denosumab administration and MRONJ were evaluated using univariate and multivariate logistic regression analyses. A receiver operating characteristic (ROC) analysis was used to determine the optimal cutoff for cumulative doses. Results: MRONJ developed in 101 patients (31.2%). Multivariate analysis identified cumulative denosumab administration (odds ratio [OR]: 1.05, 95% confidence interval [CI]: 1.03-1.06; p < 0.001) and a history of tooth extraction (OR: 4.40, 95% CI: 2.23-8.71; p < 0.001) as independent risk factors for MRONJ. ROC analysis determined an optimal cutoff of 32 cumulative doses, with an area under the curve of 0.83 (95% CI: 0.78-0.88; p < 0.0001). Conclusions: Cumulative denosumab administration and history of tooth extraction were independent risk factors for MRONJ in patients with breast cancer and bone metastases. The risk of MRONJ increased after 32 cumulative doses, providing a clinically actionable threshold for risk assessment and patient monitoring.

Background and objective We had previously conducted a phase II study (LOGIK0902/OLCSG0905 study) involving the eight-week administration of gefitinib, followed by cisplatin-based chemoradiotherapy, to treat locally advanced, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC). Despite favorable overall survival outcomes, more than half of the patients relapsed after the protocol therapy, highlighting the need to clarify the clinical significance of retreatment with EGFR-tyrosine kinase inhibitors (TKIs). We investigated the efficacy and safety of EGFR-TKI retreatment after disease progression. Materials and methods We included 14 patients who relapsed after the protocol treatment and received any type of EGFR-TKI as post-progression treatment in this sub-analysis. We evaluated the efficacy and safety of retreatment with EGFR-TKI in these patients. Results Among the 14 patients, 11 (78.6%) responded to the induction of gefitinib in the treatment protocol. After relapse, 9/14 patients (64.3%) received gefitinib, 3/14 (21.4%) received afatinib, and 2/14 (14.3%) received erlotinibmonotherapy, respectively. The median duration of post-progression EGFR-TKI treatment was 17.9 (0.7-45.5) months. The overall response rate (ORR) and disease control rate were 64.3% [9/14 patients; 95% confidence interval (CI): 35.1%-87.2%] and 85.7% (12/14 patients; 95% CI: 57.2%-98.2%), respectively. The median progression-free survival (PFS) and median survival durations after the initiation of EGFR-TKI retreatment were 11.8 months (95% CI: 5.7-20.7 months) and 47.4 months (95% CI: 31.8 months to not estimable), respectively. Adverse events were comparable to those previously reported. Conclusions Patients with disease progression after protocol therapy demonstrated sensitivity to retreatment with an EGFR-TKI, with acceptable safety.

Background:EGFR L858R mutation is associated with poorer efficacy of EGFR-tyrosine kinase inhibitors (TKIs) than EGFR Ex19del in patients with non-small cell lung cancer (NSCLC). However, ramucirumab (RAM) + erlotinib (ERL) therapy exhibited comparable efficacy between patients with L858R mutation and Ex19del mutation (median progression-free survival (PFS): 19.6 vs 19.4 months) in the RELAY study, with favorable PFS for both gene mutations at 19.4 months in the Japanese subset. Meanwhile, the FLAURA study revealed shorter PFS with osimertinib (OSI) for L858R mutation than Ex19del mutation, with poorer PFS in the Japanese subset than in the overall population. The treatment discontinuation rates of RAM + ERL and OSI in Japanese patients were 18% and 29%, respectively. Consequently, RAM + ERL may exhibit superior efficacy and safety in Japanese patients with the L858R mutation.Objectives:To evaluate the therapeutic efficacy and safety of RAM + ERL as a first-line treatment for advanced or recurrent NSCLC harboring the L858R mutation in Japanese patients.Design:A multicenter, noninterventional, retrospective cohort study.Methods and analysis:This study will involve patients with advanced or recurrent NSCLC (ECOG PS score 0–2) with L858R mutation who received RAM + ERL between November 1, 2020 and August 31, 2023, with the planned sample size of 200 patients. The primary endpoint is time to treatment failure, and the secondary endpoints are overall survival, PFS, PFS2, time to discontinuation of any EGFR-TKI, time to failure of strategy, objective response rate, disease control rate, and safety. Exploratory endpoints are effects of ERL and RAM on PD-L1 expression and neutrophil-to-lymphocyte ratio.Discussion:To the best of our knowledge, this is the first retrospective study focusing on L858R mutations associated with the RELAY regimen, providing the corresponding real-world data.Trial registration:UMIN Clinical Trials Registry identifier: UMIN000052047.