Kanazawa University Hospital

BackgroundA Japanese phase 2 trial of encorafenib plus binimetinib met the primary endpoint of the centrally assessed objective response rate in patients with unresectable BRAF V600E-mutated thyroid cancer. Consequently, encorafenib plus binimetinib has been approved in Japan. We present the health-related quality of life (HR-QoL) outcomes from the trial.MethodsThe multicenter, open-label, uncontrolled phase 2 trial enrolled patients with unresectable locally advanced or metastatic BRAF V600E-mutated thyroid cancer. HR-QoL score, one of the secondary endpoints, was assessed using the EORTC QLQ-C30 and QLQ-THY34 at baseline and during follow-up. The minimal important change (MIC) threshold was set at 10 points.ResultsWe enrolled 22 patients with BRAF V600E-mutated thyroid cancer. The median follow-up was 11.5 months. Completion rates for the questionnaires were 100% (22 of 22 patients) at baseline and 68% (15 of 22) at week 20. Until week 20, changes from baseline were below MIC at most time points in 29 of all 32 domains in QLQ-C30 and QLQ-THY34. In the other 3 domains, patients showed tendencies toward improvement (social support and appetite loss) or deterioration (joint pain) for consecutive time points. Patients with anaplastic thyroid cancer showed tendencies toward improvement for swallowing, restlessness, body image, and discomfort in the head and neck, from the first assessment after the initial treatment.ConclusionThe combination therapy of encorafenib plus binimetinib for unresectable BRAF V600E-mutated thyroid cancer was associated with generally maintained HR-QoL. Considering the efficacy and safety data from the trial, the regimen may provide clinical benefits while maintaining HR-QoL.

ABSTRACT In this study, we examined clinical and cohort data to explore the potential renoprotective effects of natto (fermented soybeans) consumption and its relationship with D‐amino acids. In a clinical study, ten healthy adults consumed one 40‐g pack of natto three times in a single day, and plasma and urine samples were collected 1 h and 24 h after intake. In a 5‐year cohort of 295 adults, natto intake was categorized as none (0 g/day), low (1–10 g/day), middle (11–25 g/day), or high (> 25 g/day). The plasma and urinary D‐alanine levels increased significantly after natto consumption. In the cohort, the adjusted mean annual changes in estimated glomerular filtration rate (eGFR, mL/min/1.73 m 2 ) were −1.41, −0.78, −1.01, and −1.01 for the none, low, middle, and high groups, respectively. Low natto intake was significantly associated with a slower decline in eGFR, although no dose‐dependent trend was observed. No significant differences in gut microbiota diversity or composition were found across intake groups. Natto consumption was associated with increased plasma D‐alanine levels and a slower decline in renal function. Further studies are warranted to clarify the mechanisms underlying these associations.

Antibody-drug conjugates (ADCs) are emerging as a promising class of targeted cancer therapy. Trastuzumab deruxtecan (T-DXd), a human epidermal growth factor receptor 2 (HER2)-directed ADC, has demonstrated clinical efficacy in HER2-positive gastric and breast cancers, as well as in HER2-mutant non-small cell lung cancer. However, the development of acquired resistance limits their long-term efficacy. To elucidate the resistance mechanism, we established T-DXd-resistant cell lines derived from HER2-amplified gastric xenografts (N87 acquired resistance [AR]) and leptomeningeal carcinomatosis (Calu-3 AR) lung cancer cells. N87 AR cells exhibited cross-resistance to T-DXd, payload DXd, and topoisomerase I inhibitor SN-38 despite preserved HER2 expression and intact drug internalization. As payload resistance-related molecules, ATP-binding cassette (ABC) transporter ABCG2 and ABCB1 were markedly upregulated in N87 AR and Calu-3 cells, respectively. Inhibition of ABCG2 and ABCB1 in N87 AR and Calu-3 cells, respectively, through siRNA-mediated knockdown restored T-DXd sensitivity in both models. As a strategy to overcome resistance, pharmacological inhibitors of ABCG2 and ABCB1 restored the T-DXd sensitivity of N87 AR and Calu-3 cells, respectively. Moreover, BB-1701, a novel HER2-ADC containing eribulin as a payload, to which N87 AR cells are sensitive, exhibited antitumor effects in N87 AR cells invitro and invivo. These findings indicate that ABC transporter-mediated drug efflux is an important mechanism underlying T-DXd resistance in HER2-positive gastric and lung cancer models. Furthermore, our study suggests that both targeting drug efflux pathways and utilizing alternative payloads may be effective strategies for overcoming T-DXd resistance in HER2-positive gastric and lung cancers.

Neuroblastoma is the most common extracranial solid tumor in children and often requires complex, multimodal treatment. A major advancement in its treatment has been the development of metaiodobenzylguanidine (MIBG), a norepinephrine analog, for diagnostic imaging and targeted radiotherapy. This review provides a comprehensive overview of the clinical applications and recent advancements of 131I-MIBG in neuroblastoma treatment. The agent has exhibited substantial efficacy in newly diagnosed and relapsed or refractory disease, through strategies such as monotherapy, tandem dosing, and high-dose administration with stem cell transplantation support. Combination regimens incorporating radiosensitizers, chemotherapeutic agents, and novel targeted approaches-including histone deacetylase inhibitors and immunotherapy-have further broadened its therapeutic scope. Challenges remain, including nonavid tumors, radiation-related risks, and logistical constraints. However, with the recent regulatory approval of 131I-MIBG for neuroblastoma treatment in Japan, its role is expected to expand, paving the way for improved outcomes and more personalized, targeted approaches in pediatric oncology.

Estimated glomerular filtration rate (eGFR) slope, which quantifies the annual change in kidney function using longitudinal measurements of eGFR, has emerged as a critical surrogate endpoint for chronic kidney disease progression in clinical trials. Accordingly, there is an increasing number of observational studies calculating the eGFR slope as an outcome or exposure of interest. To calculate the eGFR slope, linear mixed-effects models are considered statistically more efficient and therefore recommended over linear regression models constructed for each individual. Linear mixed-effects models can account for both fixed effects at the population level and random effects, which allow for subject-specific intercepts and slopes—e.g. individual-specific variation from the population mean. We introduce the practical implications of linear mixed-effects models using R programming: calculating an individual’s eGFR slope and comparing mean eGFR slopes between groups. This article is based on the hands-on seminar at the annual meeting of the 68th Japanese Society of Nephrology in 2025.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10157-026-02835-8.

<title>Abstract</title> <italic> <bold>Background:</bold> </italic> Female cancer survivors who received their diagnosis during adolescence or young adulthood may experience adverse effects of the treatment on their reproductive health, resulting in significant psychological and psychosocial burdens. These reproductive health concerns provoke profound conflicts regarding femininity and life trajectory, underscoring the importance of understanding their lived experiences within the context of cancer survivorship. This study aimed to elucidate the lived experience of reproductive health concerns among female cancer survivors who developed cancer as adolescents or young adults. <italic> <bold>Methods:</bold> </italic> <bold/> This study used a descriptive phenomenological approach. Semi-structured interviews were conducted with 19 female cancer survivors who developed cancer as adolescents or young adults and who either had a history of chemotherapy or radiation therapy or were undergoing treatment that prohibits pregnancy. Data were analyzed using the Colaizzi Model. <italic> <bold>Results:</bold> </italic> <bold/> Three clusters, namely “Concerns about loss,” “Constraints imposed by social norms,” and “Coming to terms with concerns about loss,” and 11 themes were extracted. The themes included “Concerns about the impact of treatment toxicity on fertility,” “Concerns about inability to fulfill the maternal role,” “Loss of ability to conceive naturally,” “Stigma associated with expectations to prioritize the maternal role over fertility,” “Prioritizing survival,” and “Concerns about loss of feminine identity,” among others. <italic> <bold>Conclusion:</bold> </italic> <bold/> The impact on reproductive health raises strong awareness of the effects on one’s future and family, which can cause wavering trust in one’s body and feelings of guilt about the inability to fulfill maternal roles. These concerns relate to social role expectations and self-stigma, leading to potential identity crises.

Double-tract reconstruction is commonly performed after proximal gastrectomy to prevent gastroesophageal reflux and ensure adequate nutrition. We developed a modified double-tract reconstruction intervention, denominated the NI method, in which the anastomosis between the remnant stomach and jejunum was strategically configured to optimize food passage and suppress gastroesophageal reflux. This retrospective study included patients with upper-third gastric cancer and adenocarcinoma of the esophagogastric junction who underwent proximal gastrectomy with either conventional or NI-modified double-tract reconstruction at two institutions. Postoperative outcomes, including body weight loss and incidence of reflux esophagitis, were compared. In total, 115 patients underwent proximal gastrectomy with double-tract reconstruction, including 35 with the NI method and 110 using the conventional method. No significant differences were observed in the baseline characteristics between the two groups. The incidence of reflux esophagitis was significantly lower in the NI group (0% vs. 14.3%, P = 0.032). Although not statistically significant, the NI group showed consistently lower weight loss rates, with approximately 2% less reduction at both 6 and 12months after surgery. The NI-modified double-tract reconstruction is a safe and function-preserving technique for proximal gastrectomy. The unique gastrojejunostomy design may contribute to reduce reflux and achieve better nutritional outcomes by restoring more physiological food passage.