Sotorasib and adagrasib, which are KRAS G12C inhibitors, have shown favorable clinical results mainly in non-small cell lung cancer (NSCLC) and have already been introduced into clinical practice. However, for patients with non-G12C mutations that account for the majority, such as G12D, G12V, and G13D, effective targeted therapies have still not been established. Setidegrasib (ASP3082) is a first-in-class proteolysis-targeting chimera molecule (PROTAC) that targets the KRAS G12D mutation. Phase Ⅰ trial targeting previously treated patients with advanced solid tumors harboring KRAS G12D mutations has been initiated, and the latest results were reported in the N Engl J Med in March 2026. Daraxonrasib (RMC-6236) is a pan-RAS inhibitor that targets all ON-state RAS (KRAS, NRAS, HRAS) by forming a specific pocket spanning the Switch Ⅰand Switch Ⅱ regions of KRAS through a mechanism called tri-complex/molecular glue. Currently, multiple international collaborative phase Ⅲ trials on RMC-6236, mainly focusing on PDAC and NSCLC, are underway. The development of new drugs targeting molecules other than KRAS G12C is progressing rapidly, and in KRAS mutation-positive solid cancers where prognosis was difficult to improve with conventional chemotherapy, there is a high possibility that the existing standard treatments will be significantly revised.
Cytodiagnosis is an effective screening method for early cancer detection. In cytodiagnosis, a cytotechnologist examines cell specimens collected from the target organ under a microscope. The cytotechnologist diagnose cancer by identifying precancerous or cancerous cells based on differences from normal cells. Cytology is applicable to various kinds of human organs, and one of common cancer diagnosis methods. We have been developing a support system for cytodiagnosis by identifying the types of cells contained within whole‒slide images, which are cellular specimen images. This article introduces our cytodiagnosis support system and its underlying technology.
A 50-year-old female patient noticed a mass and pain in her left breast, and needle biopsy revealed mucinous carcinoma that was negative for hormone receptors and positive for HER2/neu. After further examination, she was diagnosed with left breast cancer, cT3N2aM1 (bone), cStage Ⅳ, and was scheduled to start trastuzumab + pertuzumab + docetaxel (HPD) and denosumab. However, she was urgently admitted to the hospital due to pain caused by bone metastasis, and radiation therapy was performed. After discharge from the hospital, she was started on HPD and zoledronic acid treatment. After 6 doses of HPD, because of Grade 2 lower leg edema, treatment was continued with trastuzumab + pertuzumab (HP) and zoledronic acid only. Eighteen months after the first presentation, she complained of nausea and headache and was diagnosed with breast cancer brain metastasis. Therefore, whole brain irradiation was performed. HP was continued after radiation therapy, but headaches reappeared 33 months after the first presentation, accompanied by recurrence of brain metastasis. Trastuzumab deruxtecan was initiated, and the lesions had almost disappeared on the MRI scan 3 months later. The treatment is ongoing without any major adverse events.
BACKGROUND:The Japanese Guidelines for Diagnosis and Treatment of Lung Cancer recommend concurrent chemoradiotherapy (CRT) with cisplatin plus etoposide (PE) for limited-stage small cell lung cancer (LS-SCLC). When cisplatin administration is difficult, carboplatin plus etoposide (CE) with either sequential or concurrent thoracic radiotherapy is selected. While overseas studies have shown no significant difference in overall survival between PE and CE, evidence in Japan remains limited. METHODS:We retrospectively compared progression-free survival (PFS) between patients treated with PE and those treated with CE among LS-SCLC cases that received CRT between March 2005 and March 2025. RESULTS:A total of 43 patients were included (PE: 24, CE: 19). Most CE patients (89.5%) received CBDCA (AUC5) plus ETP (80 mg/m2). The median PFS was 13.5 months for PE (95%CI: 10.0-NA) and 9.9 months for CE (95%CI: 6.8-NA) (p = 0.369). The adjusted hazard ratio for PE versus CE was 0.85 (95% CI: 0.37-1.97; p = 0.702). The incidence of grade ≥3 neutropenia was 95.8% in PE and 89.5% in CE (p = 0.575), whereas febrile neutropenia occurred in 50.0% and 15.8% of patients, respectively (p = 0.026). CONCLUSION:In this retrospective study of patients with LS-SCLC treated with CRT, no clear differences in PFS or OS were observed between the PE and CE regimens.
Case 1: A 64-year-old woman underwent mastectomy for left breast cancer. A CT scan 5 years 9 months postoperative showed abdominal wall swelling, irregular soft tissue tumor, and irregular peritoneal thickening. She received chemotherapy for 2 years 4 months. Case 2: A 62-year-old woman underwent mastectomy for right breast cancer. A CT scan 10 years postoperative showed numerous nodules in the mesenterium and a swollen intestinal wall of the transverse colon and rectum. She received chemotherapy for over 2 years 9 months. Recurrence of peritoneal dissemination after resection for breast cancer is rare. When peritoneal dissemination is detected after breast cancer surgery, possible breast cancer recurrence should be considered when administering diagnosis and treatment.
A male patient in his 60s underwent proximal gastrectomy for adenocarcinoma of esophagogastric junction. The pathology result was UE, Type 4, 75 × 45 mm, tub1 > por2, pT4a, pN1, CY1. Then, chemotherapy with a 2-course S-1/CDDP was administered. This was followed by a 25-course PTX administered weekly for over 3 years. At this point, he underwent staging laparoscopy (SL). The result of lavage cytology was positive. Weekly PTX was administered again until the 39th course. Subsequently, he underwent 2nd SL and lavage cytology was negative. He stopped the treatment. After 1 year he received 3rd SL and lavage cytology was negative. The CT scan 5 years later showed no recurrence, and he was deemed cured. Performing SL multiple times after surgery was useful in determining treatment options.
Cancer-associated thrombosis is a serious complication of malignancy. Here, we report a case of concurrent arterial and venous thrombosis that occurred during neoadjuvant chemotherapy for breast cancer. A 72-year-old woman presented at the emergency department with malaise and movement difficulties after completing 2 cycles of dose-dense AC therapy. Contrast-enhanced computed tomography revealed thrombi in the aortic arch and left subclavian vein as well as splenic infarction. The patient was initially treated with intravenous heparin and was subsequently switched to edoxaban, which resulted in thrombus resolution. Hormone therapy was administered followed by surgery for breast cancer, and the patient's postoperative course was favorable. Thrombosis in this case was due to hypercoagulability induced by cancer and chemotherapy. Careful monitoring of thrombotic events is required during cancer treatment.
PURPOSE:To support the employment of breast cancer patients, it is important to reveal the factors that influence the side effects of chemotherapy on employment. However, there are still a few reports on the factors regarding the side effects of breast cancer chemotherapy and employment. In this study, we report on the employment status of patients with first-episode breast cancer who were treated with dd EC before surgery. SUBJECTS:Patients who underwent cancer treatment at Hospital of the University of Occupational and Environmental Health between January 2023 and December 2024 and met the following inclusion criteria. 1 ) Patients with first-episode breast cancer, 2 ) Patients who received dd EC as preoperative cancer chemotherapy, 3 ) Patients who were earning wages from employment at the start of treatment, 4 ) Patients who continued to work at the start of treatment. METHODS:We retrospectively investigated side effects and employment status within 30 days of the start of dd EC therapy based on electronic medical record data. RESULTS:Ten patients continued to work at the start of chemotherapy. The 10 patients who continued to work completed the planned course. There were no postponements of treatment due to side effects during the planned treatment period. There were no changes in work duties for any of the patients; one of the 10 patients voluntarily made work adjustments. There were no adjustments to the work environment for any of the patients. Four out of 10 patients had their working hours and schedule changed after consultation between the patient and the company. CONCLUSION:Our hospital has established the department of support for balancing work and medical treatment, which determines the appropriateness of work for patients who visit the hospital, as well as the School and Work Support Center to assist patients in balancing work and medical treatment. Since side effects were limited to Grade 2, it is thought that patients were able to continue working by taking the initiative in discussing with their workplaces and taking mitigating measures such as shortening their working hours.
Recent advances in artificial intelligence (AI) technologies have substantially expanded the role of pathological image analysis beyond improvements in diagnostic accuracy and efficiency. These developments now enable the integration of histopathological images with non-image data, prediction of treatment response and prognosis, and reduction of the workload for medical professionals. In this review, we provide an overview of representative analytical methods for pathological images, as well as approaches for predicting biomarkers and therapeutic responsiveness directly from histological images. We summarize key studies across major cancer types, pan-cancer investigations, and examples that have been successfully implemented in clinical practice. Additionally, we introduce emerging frameworks such as quantitative analysis of cellular components and tumor microenvironments, pathology foundation models, mRNA expression-based treatment response prediction, integration with spatial transcriptomics data, and applications in clinical trial design. Despite this progress, several challenges remain, such as limited availability of large-scale, high-quality datasets, domain shift across institutions, lack of model interpretability, potential biases, and significant barriers to clinical implementation and regulatory approval. Nevertheless, future developments are expected to enable the simultaneous estimation of multiple biomarkers from a single pathological image, potentially eliminating the need for additional tests. Ultimately, such advances may facilitate rapid, patient-specific drug selection and contribute to more efficient and personalized cancer treatment.
Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has been established as a standard of care in selected patients with relapsed or refractory large B-cell lymphoma (LBCL). Unlike conventional cytotoxic chemotherapy, CAR T-cell therapy has unique immune-related adverse events, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Therefore, successful management of these toxicities are crucial for the safe and effective delivery of CAR T-cell therapy. In particular, severe ICANS can be associated with life-threatening complications and poor neurological outcomes. ICANS is thought to develop as a result of excessive cytokine production associated with CAR T-cell activation, as well as on-target/off-tumor effect of CD19 expression. Clinically, it presents with a broad spectrum of neurological manifestations, ranging from mild symptoms such as cognitive impairment and aphasia to severe manifestations including seizures, depressed level of consciousness, and cerebral edema. Because clinical findings are often nonspecific, the diagnosis of ICANS can be challenging. Nevertheless, given its potential for rapid progression, early recognition and careful monitoring are essential for optimal clinical management. With regard to treatment corticosteroids have been the mainstay of treatment for ICANS in Japan. Recently, however, prophylactic and therapeutic interventions using the interleukin-1 receptor antagonist, anakinra, have attracted attention as a novel treatment option, particularly in Western countries. In this review, we summarize the currently available data on ICANS associated with anti-CD19 CAR T-cell therapy, focusing on its pathophysiology, clinical features, diagnostic approach, and management strategies.
KRAS G12C has emerged as a clinically important therapeutic target in non-small cell lung cancer (NSCLC), representing a major advance in the treatment of KRAS-driven malignancies. The development of covalent inhibitors targeting the switch-Ⅱ pocket of inactive, GDP-bound KRAS has transformed a previously undruggable oncogene into a molecularly actionable target. First-generation KRAS G12C inhibitors, including sotorasib and adagrasib, have demonstrated clinically meaningful activity in previously treated NSCLC; however, their benefit is limited by acquired resistance, which arises through secondary KRAS alterations, bypass pathway activation, and adaptive reactivation of downstream MAPK signaling. In addition, treatment-related hepatotoxicity, particularly in the setting of prior or closely sequenced immune checkpoint inhibitor exposure, has emerged as an important clinical concern. Multiple next-generation KRAS G12C inhibitors, such as divarasib, glecirasib, and olomorasib, are currently under clinical development, with early evidence suggesting improved potency, selectivity, and tolerability. Furthermore, combination strategies incorporating immune checkpoint inhibitors and upstream or downstream pathway-targeted agents, including SHP2, SOS1, and MEK inhibitors, are being actively investigated to enhance the depth and durability of response. More recently, the advent of RAS (ON) inhibitors, exemplified by daraxonrasib (RMC-6236), has introduced a distinct therapeutic paradigm by directly targeting active RAS through a tri-complex mechanism. As the therapeutic landscape continues to evolve, optimal treatment selection will require integrated consideration of molecular heterogeneity, resistance mechanisms, toxicity profiles, and patient-centered shared decision-making.
We retrospectively investigated the outcome of BCG intravesical instillation therapy for patients with non-muscle invasive bladder cancer. From 2011 to 2019, a total of 79 patients had received BCG intravesical instillation therapy for non-muscle invasive bladder cancer. Of these 79 patients, 62 were included in this study. The protocol of BCG intravesical instillation therapy was as follows: instillation once per week for 6 consecutive weeks as induction, followed by instillation twice (once per week for 2 consecutive weeks) at each of 4, 6 and 12 months after TUR-BT as maintenance. BCG completion rate was 42%. The most frequent reasons for BCG discontinuation were adverse events of BCG treatment (70%). Two-year bladder non-recurrence survival was 72%. BCG completion group showed a statistically significant better bladder non-recurrence survival compared to BCG non-completion group. However, when we focused on the patients who discontinued BCG treatment only due to adverse events, bladder non-recurrence survival in this patient group was not different from BCG completion group. In conclusion, adverse events resulting in discontinuation of BCG treatment seem to be a prognostic factor for the efficacy of BCG treatment. But from the perspective of patient's quality of life, a better management is required to prevent adverse events of BCG treatment and to promote the BCG completion rate.
KRAS mutations represent one of the most prevalent oncogenic alterations, occurring in approximately 20% of human cancers. Although KRAS had long been regarded as"undruggable,"the identification of a druggable pocket has catalyzed rapid progress in the development of targeted therapeutics. To date, the only approved KRAS-directed agent in Japan is sotorasib, a GDP-state inhibitor specific for the KRAS G12C mutation. However, a diverse array of next-generation strategies-including pan-KRAS inhibitors, pan-RAS inhibitors, tri-complex inhibitors, and targeted protein degradation modalities-are currently under active investigation. These advances have drawn increasing attention to the functional heterogeneity and differential druggability among distinct KRAS mutation subtypes, as well as organ-specific biological differences that had previously received limited consideration. Moreover, as with other molecularly targeted therapies, multiple resistance mechanisms to KRAS inhibition have been reported, underscoring the need for therapeutic strategies capable of overcoming or preventing treatment resistance.
Artificial intelligence (AI) technologies are rapidly being introduced into the medical device field, particularly in the form of software as a medical device (AI-SaMD), for which regulatory approvals are increasing. In the United States and Europe, many approved AI-SaMD products have been implemented in medical imaging applications, such as computed tomography (CT) and magnetic resonance imaging (MRI). Similar trends are observed in Japan, where approved AI-SaMD products have been implemented for endoscopy, laparoscopy, and CT. In gastrointestinal endoscopy, several randomized controlled trials have demonstrated that AI-assisted systems improve adenoma detection rate and reduce miss rate, contributing to overall procedural quality. In diagnostic imaging, AI has been used to develop techniques that reduce radiation dose while maintaining diagnostic performance, and has also been explored for use in screening examinations. In surgical assistance, the integration of AI with extended reality (XR) technologies has enabled intraoperative visualization of anatomical structures and instrument tracking, offering novel strategies for navigation. In pathology, deep learning models have shown potential to predict molecular subtypes and treatment responsiveness in malignancies. Collectively, these findings indicate that medical AI is transitioning from research-based technologies toward clinical implementation and, in some domains, commercialization. Future challenges include standardization, explainability, and effective integration into clinical workflows to ensure safe and sustainable adoption.
BACKGROUND:Tisotumab vedotin (TV), an antibody-drug conjugate targeting tissue factor (TF), was approved in Japan in 2025 for the treatment of recurrent/metastatic cervical cancer. As TF is also expressed on the ocular surface, TV frequently causes ocular adverse events (OAEs), necessitating strict management. This paper reports on the established'onco-ophthalmology'collaboration system developed to manage these risks. METHODS:A multidisciplinary protocol involving medical oncologists, ophthalmologists, pharmacists, and nurses was implemented. Key components included pre-treatment ophthalmic assessment, pharmacist-led guidance on prophylactic eye drops, cooling during treatment, and a rapid referral system upon symptom onset. RESULTS:Between June and October 2025, 5 patients received TV therapy. One case (20%) developed Grade 2 pseudomembranous conjunctivitis. Immediate ophthalmic evaluation revealed neutrophilic infiltration without infectious findings on smear examination. Symptoms resolved within 7 days of steroid treatment. CONCLUSION:Whilst preventative measures are crucial, ocular complications remain possible. This case demonstrates that early diagnosis and effective management are achievable through the onco-ophthalmology liaison system, ensuring the safe continuation of TV therapy.
A 72-year-old man was diagnosed with advanced gastric cancer with severe gastric stenosis, lymph node metastasis, and portal vein invasion. He underwent ileo-gastrostomy, then received chemotherapy using 4 cycles of S-1 and 2 cycles of SOX. The response to this therapy was judged PD; thus, second-line therapy of wPTX + RAM was introduced, although icterus and ascites were recognized then. After a single injection of wPTX + RAM, G4 neutropenia, anorexia, and severe ascites were observed. Thus, the chemotherapy was discontinued. At that point, he had been diagnosed with severe liver cirrhosis, and internal treatment was introduced. Six weeks after the last injection of anti-cancer drugs, CT revealed tumor shrinkage and highly reduced serum CEA, although ascites increased. Subsequently, ascites and general condition gradually recovered without anti-cancer therapy. One year after the last injection of anti-cancer drugs, the primary tumor, lymph node metastasis, and portal vein invasion were not observed on CT and endoscopy, and the patient was judged cCR. This rare case demonstrated prolonged effect of wPTX + RAM that caused the depression of liver metabolism. Therefore, anti-cancer immune response has been induced by an unknown mechanism.
The analysis of cell-free DNA (cfDNA) in blood is expected to serve as a new diagnostic method for early cancer detection and treatment monitoring by examining trace amounts of ctDNA derived from cancer cells. In cancer patients, ctDNA circulates in the bloodstream, and thanks to technological innovations in next-generation sequencing (NGS) and the analysis of fragmented DNA at low levels, it is now possible to non-invasively detect the presence and type of cancer. Multi-cancer early detection (MCED) is a method for detecting cancer early and identifying its specific type by analyzing cfDNA fragment characteristics, ctDNA somatic variants, and DNA methylation status; some MCED tests are already commercially available. However, when used as a standalone test, MCED faces challenges in early detection reliability and the risk of overdiagnosis, necessitating improvements in sensitivity and specificity, as well as clinical efficacy evidence. For this reason, MCED is currently positioned to complement existing screening methods. Furthermore, in addition to analyzing DNA fragment characteristics and methylation, machine learning is expected to enable more accurate detection. However, challenges remain, such as improving sensitivity in clinical stage Ⅰ and reducing false positives, making further research progress essential. Nevertheless, MCED holds great potential for personalized cancer prevention. This review discusses early cancer diagnosis using cfDNA analysis and the technological advancements in this field.
Recent advances in pathology foundation models have markedly improved the accuracy and generalizability of histopathological image analysis in breast cancer. However, the mechanisms of resistance to CDK4/6 inhibitors in hormone receptor-positive, HER2-negative advanced breast cancer remain incompletely understood. This article outlines a strategy to identify therapeutic targets by integrating pathology AI with spatial transcriptomics. We developed AI-directed spatial transcriptomics (AID-ST), a framework that compares gene expression profiles between drug-sensitive and drug-resistant regions identified by pathology AI. In a preliminary analysis of clinical breast cancer specimens, this approach suggested that KRAS pathway activation is a major driver of resistance, accompanied in part by Polycomb dysregulation, RB loss, PI3K pathway alteration, and acquisition of stem-like features. Additional spatial analyses of paired pre- and post-treatment specimens supported these findings and further suggested a role for the tumor microenvironment, including EMT- and IL6/JAK/STAT3-related changes, in promoting resistant phenotypes. These results indicate that integrating pathology AI with spatial transcriptomics may enable systematic classification of resistance subtypes and prioritization of actionable therapeutic targets in breast cancer.
A 67-year-old man diagnosed with multiple synchronous malignancies, including follicular lymphoma and lung adenocarcinoma, underwent 1 cycle of chemotherapy with obinutuzumab and bendamustine, followed by lower lobectomy. After surgery, adjuvant therapy with osimertinib was administered. The patient showed no evidence of lymphoma or lung cancer recurrence for over a year after surgery. Multiple malignancies involving both hematological neoplasms and solid tumors are rare, to optimize treatment and improve patient outcomes, consultations with multiple medical departments are warranted.
In Japan, the adoption rate of electronic medical records (EMR) in general hospitals has surpassed 50%, leading to the rapid digitization of medical information. However, core components such as clinical notes and nursing records remain accumulated as unstructured data in "natural language" (free text). Consequently, their secondary utilization relies heavily on human interpretation, presenting significant challenges. This paper details the development and utility of a system that automatically generates high-precision patient summaries from EMR free text, leveraging large language models (LLMs) and retrieval-augmented generation (RAG) technologies, which have undergone dramatic evolution in recent years. We developed a medical-specific LLM trained on data accumulated at Tohoku University Hospital and conducted demonstration experiments on: 1) the automated generation of discharge summaries from nursing records, and 2) the extraction of complex cases based on clinical trial eligibility criteria. The results demonstrated that the LLM generated summaries of quality comparable to those created by nurses, suggesting the potential for significant improvements in the efficiency of documentation tasks. Furthermore, in the context of drug discovery support, the system successfully identified cases meeting complex clinical conditions that were impossible to extract using conventional search methods. However, the risk of hallucinations inherent in generative AI was also confirmed, making human oversight (human-in-the-loop) indispensable for clinical implementation.
