Koshi Takahashi

Background/Objectives: Cancer genomic testing presents unique communication and educational challenges for healthcare providers, requiring specialized training approaches. We developed and evaluated a communication skills training program specifically designed for cancer genomic testing based on the SHARE protocol to reduce psychological distress in both medical staff and patients. Methods: A mixed-methods evaluation was conducted of a structured training program implemented across 10 institutions in Yamagata Prefecture. The program incorporated SHARE protocol-based training, role-playing sessions, and specialized modules addressing cancer genomic testing-specific challenges. Quantitative assessment utilized pre- and post-intervention questionnaires, and qualitative evaluation employed semi-structured interviews analyzed using exploratory inductive analysis. Results: Among 251 participants, 95% initially reported psychological burden when explaining cancer genomic testing results. Post-intervention, 95% reported a perceived reduction in psychological burden, with 84% expressing training satisfaction. Exploratory analyses suggested that the perceived reduction in psychological burden was significantly greater in nurses than other professionals. Qualitative analysis of 19 interviews identified two conceptual categories among healthcare providers (demand for ongoing feedback and educational reinforcement, and anxiety and response needs regarding genetic results) and four conceptual categories among patients and family members (information acquisition needs, trust in and expectations of healthcare providers, psychological burden related to genetic information, and equitable access requirements for testing). Conclusions: This educational initiative was associated with self-reported perceived reductions in psychological burden and anxiety related to cancer genomic testing communication immediately following training. The mixed-methods evaluation provides preliminary, hypothesis-generating input for curriculum development and faculty training in genomic medicine communication.

Background/Objectives: Cancer genomic testing presents unique communication and educational challenges for healthcare providers, requiring specialized training approaches. We developed and evaluated a communication skills training program specifically designed for cancer genomic testing based on the SHARE protocol to reduce psychological distress in both medical staff and patients. Methods: A mixed-methods evaluation was conducted of a structured training program implemented across 10 institutions in Yamagata Prefecture. The program incorporated SHARE protocol-based training, role-playing sessions, and specialized modules addressing cancer genomic testing-specific challenges. Quantitative assessment utilized pre- and post-intervention questionnaires, and qualitative evaluation employed semi-structured interviews analyzed using exploratory inductive analysis. Results: Among 251 participants, 95% initially reported psychological burden when explaining cancer genomic testing results. Post-intervention, 95% reported reduced psychological burden, with 84% expressing training satisfaction. Exploratory analyses suggested anxiety reduction was significantly greater in nurses than other professionals. Qualitative analysis of 19 interviews identified four conceptual categories: complex information needs requiring psychological support, uncertainty about communicating germline findings, perceived knowledge gaps in genomic counseling, and organizational support needs for sustained practice changes. Conclusions: This educational initiative demonstrated improvements in addressing critical communication challenges in cancer genomic medicine. The mixed-methods evaluation provides an educational framework for curriculum development and faculty training in genomic medicine communication.

Background/Objectives: The anti-CLDN18.2 antibody zolbetuximab has emerged as a novel therapeutic option for advanced gastric adenocarcinoma. However, robust predictive biomarkers for its efficacy remain an unmet need. Methods: Utilizing the Japanese Center for Cancer Genomics and Advanced Therapeutics database, we retrospectively analyzed the clinical and genomic profiles of 49 patients with gastric adenocarcinoma who received zolbetuximab-containing regimens. In line with Japanese health insurance regulations, these patients were deemed to have CLDN18.2-positive tumors. We explored the association between the objective response rate (ORR) and concurrent genomic alterations, focusing on tumor mutational burden (TMB) and major mutations (TP53, ARID1A, CDH1). Results: The ORR to zolbetuximab-based therapy in this cohort was 22.2%. Statistical analysis revealed a trend toward higher clinical response in patients with lower TMB (median 1.82 in responders vs. 4.0 in non-responders; p = 0.050). Furthermore, patients without a CDH1 single-nucleotide variant also showed a suggestive trend toward better response (p = 0.086). No significant associations were found with TP53 or ARID1A alterations (p = 0.787 and p = 0.239, respectively). Conclusions: Our findings suggest that low TMB and the absence of CDH1 variants may serve as potential predictive biomarkers for response to zolbetuximab in CLDN18.2-positive gastric cancer. Prospective validation is warranted to maximize patient selection for this targeted therapy.

Background/Objectives: Metaplastic breast carcinoma (MpBC) is a rare and aggressive malignancy characterized by significant histological heterogeneity and limited response to standard chemotherapy. Due to its morphological diversity, MpBC often presents diagnostic challenges and can overlap with other mesenchymal tumors. This study aimed to characterize the genomic landscape of MpBC using a nationwide Japanese database and to explore the molecular basis of its diagnostic ambiguities and therapeutic responses. Methods: We retrospectively analyzed genomic and clinical data from 123 MpBC cases registered in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database. To evaluate diagnostic boundaries, genomic profiles of histological mimickers, including 19 cases of angiosarcoma and eight cases of myoepithelial carcinoma, were also examined. Furthermore, an exploratory single-cell RNA-sequencing analysis was performed on 3274 cells from independent MpBC datasets to investigate cellular heterogeneity and potential lineage plasticity. Results: TP53 (73.2%) and PIK3CA (46.0%) were the most prevalent genomic alterations in the MpBC cohort. Exploratory analysis suggested that PIK3CA mutations may be associated with an improved disease control rate in patients receiving taxane-based therapy (p = 0.028). Comparisons with mimickers identified distinctive molecular signatures, such as MED12 and HRAS hotspot mutations, across entities. Single-cell transcriptomics identified a distinct subpopulation (7.02% of malignant cells) co-expressing epithelial and phyllodes-like signatures. Conclusions: These findings suggest that MpBC harbors hybrid malignant cell populations that may contribute to its complex morphological diversity. While the therapeutic associations are based on a limited cohort and require prospective validation, the integration of comprehensive genomic and single-cell profiling provides an exploratory framework that may potentially enhance diagnostic accuracy in the future. However, these associations remain preliminary and require prospective validation to confirm their clinical utility.

Background/Objectives: The anti-CLDN18.2 antibody zolbetuximab has emerged as a novel therapeutic option for advanced gastric adenocarcinoma. However, robust predictive biomarkers for its efficacy remain an unmet need. Methods: Utilizing the Japanese Center for Cancer Genomics and Advanced Therapeutics database, we retrospectively analyzed the clinical and genomic profiles of 49 patients with gastric adenocarcinoma who received zolbetuximab-containing regimens. Due to Japanese health insurance regulations, these patients were deemed to have CLDN18.2-positive tumors. We explored the association between objective response rate (ORR) and concurrent genomic alterations, focusing on t umor m utational b urden (TMB) and major mutations (TP53, ARID1A, CDH1). Results: The ORR to zolbetuximab-based therapy in this cohort was 22.2%. Statistical analysis revealed a trend toward higher clinical response in patients with lower TMB (median 1.82 in responders vs. 4.0 in non-responders; p=0.050). Furthermore, patients without a CDH1 single nucleotide varian t also showed a suggestive trend toward better response (p=0.086). No significant associations were found with TP53 or ARID1A alterations (p=0.787 and p=0.239, respectively). Conclusions: Our findings suggest that low TMB and the absence of CDH1 variants may serve as potential predictive biomarkers for response to zolbetuximab in CLDN18.2-positive gastric cancer. Prospective validation is warranted to maximize patient selection for this targeted therapy.

Phyllodes tumors are rare fibroepithelial neoplasms of the breast, and their malignant forms present significant diagnostic and therapeutic challenges. This review summarizes current knowledge across the benign-to-malignant spectrum, focusing on diagnostic approaches, histopathological classification, molecular alterations, and treatment strategies. While recent molecular studies have revealed recurrent genetic mutations, their clinical implications remain under investigation. Surgical excision remains the cornerstone of treatment, and systemic therapies are generally adapted from soft tissue sarcoma protocols. Future efforts should focus on improving diagnostic accuracy, identifying molecular targets for therapy, and fostering international collaboration to advance clinical research in this rare tumor type.

Background: Improving cancer screening participation is increasingly important. However, insufficient medical and financial resources have been reported to hinder program implementation; therefore, enhancing program efficiency is crucial. Although demographic factors have been reported to correlate with public health program efficiency, it remains unclear whether this applies to cancer screening. Objectives: To evaluate the efficiency of cancer screening programs conducted in Japanese municipalities and analyze their relationship with demographic characteristics, including population size and aging rates. Design: A cross-sectional study using national open-source data from 2019. Methods: We collected data from all 1741 Japanese municipalities in 2019 using a national open-source database. After applying inclusion criteria, 1593 municipalities were analyzed. Program efficiency was measured using Data Envelopment Analysis (DEA), with inputs including the number of public health nurses, medical institutions, and healthcare expenditure per target population. Outputs were cancer screening participation rates. Logistic regression was used to examine the relationships between efficiency, population size, aging rates, and their interaction. Results: Of the 1593 municipalities analyzed, 414 (26.0%) were deemed efficient. A statistically significant interaction between aging rates and population size was observed in the model predicting screening efficiency. In municipalities with aging rates above 31.4% (95% confidence interval [CI]: 29.2-37.1), larger target populations were associated with lower efficiency. Conversely, in municipalities with over 1075 screening targets (95% CI: 552-1381), higher aging rates were linked to lower efficiency. Conclusion: This study suggests that aging rates and population size may be associated with municipal-level differences in the efficiency of cancer screening programs. Understanding the mechanism underlying this relationship could help inform resource allocation and program design. Further research is warranted to explore these relationships more deeply and to support the development of more efficient screening strategies, particularly in the context of ongoing demographic shifts.

Phyllodes tumors are rare fibroepithelial neoplasms of the breast, and their malignant forms present significant diagnostic and therapeutic challenges. This review summarizes current knowledge across the benign-to-malignant spectrum, focusing on diagnostic approaches, histopathological classification, molecular alterations, and treatment strategies. While recent molecular studies have revealed recurrent genetic mutations, their clinical implications remain under investigation. Surgical excision remains the cornerstone of treatment, and systemic therapies are generally adapted from soft tissue sarcoma protocols. Future efforts should focus on improving diagnostic accuracy, identifying molecular targets for therapy, and fostering international collaboration to advance clinical research in this rare tumor type.

Epidermal growth factor receptor 2 (ERBB2/HER2) is a critical biomarker in gastric cancer management, but the clinical implications of specific ERBB2 mutations remain poorly characterized. Methods/Results: We investigated the ERBB2 R678Q mutation, utilizing the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, which involved the analysis of 3116 gastric/gastroesophageal junction adenocarcinomas. ERBB2 mutations were identified in 130 cases, with R678Q present in 40 patients. These patients exhibited significantly lower response rates to oxaliplatin-based regimens compared to ERBB2 wild-type cases (19.0% vs. 38.0%, p = 0.03), while other ERBB2 mutations demonstrated no such resistance. No significant differences in the response were observed to the ramucirumab or nivolumab regimens. Conclusions: Our findings suggest that the ERBB2 R678Q mutation may predict a poor response to oxaliplatin-based therapy. This study provides real-world evidence supporting the potential clinical relevance of this specific ERBB2 mutation in treatment decision making for gastric cancer.

Epidermal growth factor receptor (EGFR) inhibition is crucial in treating RAS wild-type metastatic colorectal cancer, yet current testing methods may miss rare RAS variants affecting treatment efficacy. We analyzed 4122 colorectal cancer patients receiving anti-EGFR antibodies from the Center for Cancer Genomics and Advanced Therapeutics database, identifying 54 patients (1.3%) with rare RAS variants undetectable by standard testing. These patients showed significantly lower response rates to anti-EGFR therapy (28.3%) compared to RAS wild-type cases (44.6%, p = 0.003). Disease control rates were also lower in rare variant cases (60.9%) versus wild-type cases (80.0%). Most common rare variants included KRAS Q22K, A59E, and A11_G12insGA. Comprehensive genomic profiling revealed additional alterations in TP53 (90.7%), APC (87.0%), and non-V600E BRAF mutations (25.9%). Our findings suggest that rare RAS variants predict poor anti-EGFR therapy response, highlighting the potential benefit of comprehensive genomic profiling before treatment initiation. This study provides real-world evidence supporting the clinical relevance of rare RAS variants in treatment decision-making for colorectal cancer. Future studies should focus on developing cost-effective comprehensive testing strategies and evaluating alternative treatment approaches for patients with rare RAS variants.