Gifu University Hospital

Abstract Acute myeloid leukemia (AML) is an aggressive hematologic cancer characterized by proliferation of immature myeloblasts 1 . It shows profound molecular heterogeneity, which has been primarily studied through genetic abnormalities, providing the basis for disease classification, prognostication, and therapeutic choice 2–8 . However, genetic factors alone may not fully explain AML pathogenesis and diversity, while leaving the role of abnormal epigenome, particularly chromatin state, largely unexplored in a large cohort of patients. Here we show that AML is classified into 16 subgroups with distinct chromatin accessibility profiles based on ATAC-seq in 1,563 AML cases, derived from the encyclopedia of chromatin in AML (eCHROMA AML) dataset, including novel AML subgroups not previously recognized in conventional genomic classifications. By integrating multi-omics analyses of genome, transcriptome, and major histone marks, we show that these epigenetic subgroups exhibit unique features in clinical presentation, gene mutations, differentiation states, gene expression, and super-enhancer profiles, which are validated across independent cohorts. Single-cell sequencing demonstrates the presence of subgroup-specific ATAC signatures that are shared by all leukemic cells, confirming the key role of the epigenome in the ATAC-based classification. Mechanistically, each subgroup is associated with a distinct gene regulatory network centered on key transcription factors, where subgroup-specific super-enhancers play a pivotal role. These ATAC subgroups also have prognostic significance independent of genomic classification, and help reveal unexpected drug sensitivities. In summary, ATAC-based chromatin profiling in this large sample set, combined with multi-omics data, provides new insights into AML pathogenesis beyond genomic profiling and also serves as an invaluable resource for AML research.

Abstract Introduction Maintaining dose intensity is essential for the efficacy of adjuvant S-1 chemotherapy in gastric cancer. Although pharmacist interventions can reduce toxicity and improve adherence, multicenter evidence regarding their impact on dose maintenance is limited. Aim This study aimed to evaluate the impact of continuous pharmacist intervention on treatment completion and relative performance (RP) value in patients receiving adjuvant S-1 chemotherapy for gastric cancer. Methods This multicenter retrospective study analysed 225 patients across 12 institutions, categorised into continuous intervention (n=97) and non-continuous intervention (n=128) groups. Continuous intervention was defined as systematic monitoring and management for at least 50% of the treatment duration. Inverse probability of treatment weighting adjusted for baseline covariates. The primary and secondary endpoints were the eight-cycle completion rate and the RP value, respectively. Results Eight-cycle completion rate did not differ significantly between the continuous and non-continuous intervention groups (53.0% vs. 55.2%, p = 0.775), nor did the frequency of treatment modification events, including discontinuation or dose reduction. However, the RP value was significantly higher in the continuous intervention group than in the non-continuous intervention group (73.7% vs. 64.9%, p = 0.038), a finding robustly supported by sensitivity analysis between these two groups (75.1% vs. 61.1%, p = 0.0008). The continuous group maintained a high intervention rate (89.1%) throughout the final cycle, providing significantly more supportive care interventions than the non-continuous intervention group (53.2% vs. 4.9%, p < 0.001). Conclusion Although continuous pharmacist intervention did not improve the binary completion rate, it was essential for maintaining RP values above the clinically essential 70% threshold through proactive toxicity management and dynamic dose optimization. These findings suggest that systematic pharmaceutical care contributes significantly to ensuring the quality and intensity of adjuvant chemotherapy.

Abstract Purpose An exploratory analysis of the phase III CONSOLE study indicated that the triplet antiemetic regimen including fosnetupitant (FosNTP) may be effective across extended overall period (0–168 h) for highly emetogenic chemotherapy-induced nausea and vomiting (CINV); however, its impact during the long-delayed phase (> 168 h) remains unclear. This study aimed to prospectively explore the benefits of FosNTPs in preventing CINV beyond 168 h in patients undergoing oxaliplatin-based chemotherapy. Methods This single-center, single-arm, prospective observational study recruited patients scheduled to receive oxaliplatin-based chemotherapy. The primary endpoint was the long-delayed (120–336 h) complete control (CC) rate. Key secondary endpoints included the long-delayed complete response (CR) rate and the overall (0–336 h) CC, CR, and total control (TC) rates. Relative risks for emetogenic events were assessed using a logistic regression model. Results The analysis included 100 patients. Most eligible patients received CapeOX (oxaliplatin + capecitabine) (92.0%). The long-delayed CC rate was 76.3%. The long-delayed CR and TC rates were 84.7% and 75.4%, respectively. Risk factors for CINV in participants who did not achieve CC during the long-delayed phase included age (odds ratio 0.954 [95% confidence interval 0.909–0.998]), female sex (8.808 [2.446–41.992]), and history of motion sickness (5.050 [1.118–27.548]). Conclusion The triplet regimen involving FosNTP demonstrated sufficient efficacy in preventing CINV in patients receiving oxaliplatin-based chemotherapy, including during the long-delayed phase. However, participants with high emetic risk factors—such as younger age, female sex, or a history of motion sickness—continued to experience suboptimal control. Trial registration number and date of registration : jRCT1030230130

Transorbital penetrating head trauma is rare but carries high mortality due to the risk of intracranial vascular injury and infection. Early vascular assessment and careful procedural planning are critical. A woman in her fifties sustained transorbital penetration by a chopstick that traversed the brainstem and extended to the posterior fossa. CT angiography demonstrated proximity to the cavernous segment of the right internal carotid artery and the posterior cerebral artery without active extravasation. Under endovascular standby with proximal balloon preparation, the foreign body was removed in a conventional angiography suite without craniotomy. Serial angiography and MRA revealed transient vascular irregularity that gradually resolved, documenting spontaneous vascular healing without the use of antithrombotic therapy. Post-treatment MRI demonstrated parenchymal injury along the penetrating trajectory without evidence of abscess formation. This case illustrates that in angiographically stable but anatomically high-risk transorbital penetrating injuries, planned extraction under endovascular standby may be a feasible option in carefully selected cases. Serial vascular follow-up is essential to detect delayed vascular changes and to confirm spontaneous vascular healing.

This study investigated the effectiveness of a protocol-based pharmacotherapy management (PBPM) system in preventing hepatitis B virus (HBV) reactivation induced by chemotherapy. This protocol requires pharmacists to verify orders for hepatitis B (HB) surface antigen (HBsAg), anti-HB core antibody (HBcAb), anti-HBs antibody (HBsAb), and HBV-deoxyribonucleic acid (DNA) tests before the start of chemotherapy. Pharmacists are also required to enter any missing test orders after confirming them with physicians. We retrospectively compared the implementation rates of HBsAg, HBcAb, HBsAb, and HBV-DNA tests using the chi-squared test across the following three periods: the pre-PBPM system implementation (pre-PBPM) period (July to September 2021; n=203), the ≤6 month post-PBPM system implementation (≤6M post-PBPM) period (November 2021 to April 2022; n=453), and the >6 month post-implementation (>6M post-PBPM) period (May to July 2022; n=245). The implementation rate of HBsAg tests remained at 100% throughout the entire study period. The overall HBsAg positivity rate was 2.0% (18/901). The implementation rates of HBcAb/HBsAb tests increased significantly, from 59.6% (121/203; pre-PBPM period) to 91.2% (413/453; ≤6M post-PBPM period, p<0.001) and to 98.0% (240/245; >6M post-PBPM period, p<0.001). The HBcAb/HBsAb positivity rates and HBV-DNA implementation rates in the respective periods were 33.1% (40/121), 26.9% (111/413), and 23.8% (57/240), and 90.0% (36/40), 89.2% (99/111), and 91.2% (52/57), with no statistically significant differences observed. No cases of HBV reactivation were observed during the study period. Introduction of the PBPM system significantly contributed to the improvement in the implementation rates of HBsAb/HBcAb testing.

Abstract (Background) Breast cancer (BC) remains a leading cause of cancer-related deaths despite advances in diagnosis and treatment. Accurate evaluation of response to neoadjuvant chemotherapy (NAC), especially in HER2-positive and triple-negative subtypes, is critical. In recent years, liquid biopsy techniques, which analyze tumor-derived materials in body fluids, have emerged as promising non-invasive tools for cancer detection and monitoring. Nematodes-NOSE (N-NOSE) is a novel cancer screening test that utilizes the chemotaxis index of the nematode Caenorhabditis elegans (C. elegans). The N-NOSE method is a non-invasive diagnostic approach that falls within the broader category of liquid biopsy, which analyzes tumor-derived materials in body fluids. C. elegans possesses a highly sophisticated olfactory system and has been reported to exhibit attraction toward the urine of cancer patients while avoiding that of healthy individuals. In the current study, we aimed to clarify the ability of the N-NOSE method to predict the response to NAC in BC patients. (Materials and Methods) A total of 36 BC patients scheduled to undergo NAC followed by surgery at our institution between August 2020 and May 2023 were prospectively enrolled in this study. All patients were histologically confirmed to have BC and were deemed eligible for NAC based on clinical staging and risk stratification. Urine samples were collected from each patient at three distinct time points: prior to the initiation of NAC, immediately before surgery, and four weeks after surgery. For chemotactic assays, 0.5 μL of 1 M sodium azide, an anesthetic used to minimize the effects of adaptation, was spotted onto four points on the agar plate (urine side and non-urine side), and 1 μL of urine sample diluted 100-fold with ultra-pure water was added to two points (urine side). Approximately 100 adult nematodes were placed in the center of the plate. After roaming for 30 minutes, the number of nematodes present in area A (urine side) and the number of nematodes present in area B (non-urine side) were counted. The chemotaxis index (CI) was calculated using the following equation: Index = (Number of nematodes in area A - Number of nematodes in area B)/Total number of nematodes. The change in CI (Index Reduction Score, IRS) was calculated for three intervals: before and after NAC (IRS1), before and after surgery (IRS2), and before NAC and after surgery (IRS3). The association between IRS and treatment efficacy was statistically evaluated using receiver operating characteristic (ROC) curve analysis. (Results) Among the 36 patients enrolled, the median age was 51 years (range: 35-77). Thirteen patients (36.1%) achieved pathological complete response (pCR), while sixteen patients (44.4%) achieved pathological partial response (pPR). When the treatment response included CR or PR, the area under the ROC curve (AUC) for IRS1, IRS2, and IRS3 were 0.53 (95% CI: 0.19-0.78), 0.76 (95% CI: 0.56-0.96), and 0.66 (95% CI: 0.37-0.96), respectively. Notably, when only pCR cases were analyzed, the AUCs were 0.58 (95% CI: 0.34-0.82) for IRS1, 0.64 (95% CI: 0.40-0.88) for IRS2, and 0.75 (95% CI: 0.54-0.95) for IRS3, indicating that IRS3 had the highest predictive value for pCR. In this study, some pCR cases exhibited minimal residual intraductal disease before surgery, which was subsequently removed during surgery, potentially resulting in a higher IRS3 compared to IRS1. (Conclusion) The IRS measured by the N-NOSE method may accurately reflect the efficacy of NAC in BC patients. Furthermore, N-NOSE may be able to detect minimal or subclinical residual tumors after NAC, which are usually grouped clinically but may differ in their biological characteristics. Further large-scale, multicenter prospective studies are warranted. Citation Format: A. Nakakami, Y. Tokumaru, Y. Niwa, R. Mori, M. Okawa, Y. Sato, H. Hatakeyama, T. Hirotsu, E. di Luccio, N. Matsuhashi, M. Futamura. N-nose as a non-invasive biomarker for predicting neoadjuvant chemotherapy response in breast cancer patients [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 PS4-03-29.

Abstract Background: Antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) have revolutionized breast cancer (BC) treatment, providing superior efficacy that allows for extended treatment durations. Nausea and vomiting (NV) are among the most frequent adverse effects associated with T-DXd and SG, with nausea rates of &amp;gt;70% for T-DXd and &amp;gt;60% for SG in BC clinical trials. According to antiemetic guidelines, patients receiving T-DXd and SG are at moderate-to-high risk for NV and should routinely receive prophylaxis with an NK1 receptor antagonist (RA)-containing regimen. With limited real-world data on antiemetic efficacy in the ADC setting, a survey of international healthcare providers (HCPs) was conducted to assess their experience. Methods: At SABCS 2024, HCPs completed a brief web-based survey to assess their experiences and perceptions of ADC emetogenicity and approaches to antiemetic prophylaxis. Target participants included HCPs familiar with ADCs who manage patients with BC. Eligible participants completed the survey on computers located in the exhibit hall. Results: Of 209 HCPs surveyed, 112 were eligible. Most were oncologists (69%) or hematologist/oncologists (21%) who spent 73% of time in patient care; nearly half were US-based (46%). Among all HCPs, 80% reported using ADCs in practice and/or in clinical trials; 99% had experience with T-DXd and 87% with SG. Among HCPs using T-DXd and SG, 78% and 83%, respectively, perceived them as either highly (32% and 28%) or moderately (46% and 55%) emetogenic. NV reported by HCPs in this survey was much lower than in the T-DXd and SG clinical trials; HCPs reported that 30%, 25% and 15% of their BC patients treated with T-DXd experience N and/or V during the acute (0-24 hours), delayed (days 2-5), and long-delayed (beyond day 5) phases, respectively. Similarly, the reported NV rates were 29%, 26% and 13%, respectively, for SG. HCPs reported that 88% of patients treated with any ADCs in an average month receive antiemetic prophylaxis; however, only 39% of HCPs report exclusively using a guideline-recommended NK1 RA regimen with T-DXd or SG. The majority of HCPs (94%) reported implementing some type of dose adjustments of ADCs due to NV. A third to nearly half of HCPs had at least sometimes implemented an ADC dose reduction or delay due to NV while a quarter reported interrupting or discontinuing ADC treatment (Table). More than half reported using rescue medication at least sometimes for delayed NV. Conclusions: This survey highlights a gap between evidence and HCP perceptions regarding NV with T-DXd and SG, and reveals higher-than-expected dose reductions, likely reflecting suboptimal adherence to antiemetic guidelines. As ADCs gain prominence in BC treatment, these findings underscore the need for education and guideline-implementation to optimize NV prevention. Citation Format: L. S. Schwartzberg, L. Licata, G. Bianchini, Y. H. Park, E. J. Roeland, M. Massagrande, F. Dato, H. Iihara, F. Scotte, K. Jordan, M. Aapro, H. S. Rugo. Examining Antiemetic Management with Antibody-Drug Conjugates (ADCs) in Patients with Breast Cancer: Healthcare Provider (HCP) Insights from a SABCS Survey [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 PS1-01-13.

This study aimed to examine the effects of concomitant use of proton-pump inhibitors (PPIs) on the survival outcomes in patients with endocrine-sensitive chemotherapy-naïve advanced breast cancer (BC) treated with palbociclib or abemaciclib. This multicenter, retrospective study was conducted at five hospitals in Japan. Data were collected from consecutive patients treated with palbociclib or abemaciclib in combination with endocrine therapy as first-line treatment for endocrine-sensitive chemotherapy-naïve advanced BC between December 2017 and August 2022. Associations between concomitant PPI use and survival outcomes were analyzed. Among 202 patients, 38 (19%) were concomitant PPI users. In the palbociclib population (n = 123), concomitant PPI use was associated with a trend toward decreased progression-free survival (PFS) and a significant reduction in overall survival (OS; crude hazard ratio [HR], 1.67; 95% confidence interval [CI], 0.86–3.00 and crude HR, 3.51; 95% CI, 1.53–7.64, respectively). In multivariable analyses, consistent results were obtained (adjusted HR, 1.29; 95% CI, 0.66–2.53 and adjusted HR, 3.23; 95% CI, 1.28–7.67, respectively). In contrast, concomitant PPI use did not significantly affect either PFS or OS in the abemaciclib group (n = 79). Concomitant PPI use decreased the efficacy of palbociclib regardless of the formulation, with no such impact observed with abemaciclib.