論文

We introduce J-ORA, a novel multimodal dataset that bridges the gap in robot perception by providing detailed object attribute annotations within Japanese human-robot dialogue scenarios. J-ORA is designed to support three critical perception tasks, object identification, reference resolution, and next-action prediction, by leveraging a comprehensive template of attributes (e.g., category, color, shape, size, material, and spatial relations). Extensive evaluations with both proprietary and open-source Vision Language Models (VLMs) reveal that incorporating detailed object attributes substantially improves multimodal perception performance compared to without object attributes. Despite the improvement, we find that there still exists a gap between proprietary and open-source VLMs. In addition, our analysis of object affordances demonstrates varying abilities in understanding object functionality and contextual relationships across different VLMs. These findings underscore the importance of rich, context-sensitive attribute annotations in advancing robot perception in dynamic environments. See project page at https://jatuhurrra.github.io/J-ORA/.

Although the 5-year relative survival rates for resectable solid tumors have improved over the past few years, the risk of postoperative recurrence necessitates effective monitoring strategies. Recent advancements in molecular residual disease (MRD) testing based on circulating tumor DNA (ctDNA) analysis have shown considerable promise in the context of predicting recurrence; however, significant barriers to widespread clinical implementation remain—mainly, low awareness among healthcare professionals, high costs, and lack of standardized assays and comprehensive evidence. This position paper, led by the Japan Society of Clinical Oncology, aims to establish a common framework for the appropriate clinical use of MRD testing in a tumor type-agnostic manner. It synthesizes currently available evidence, reviews region-specific clinical trends, addresses critical clinical questions related to MRD testing, and offers recommendations to guide healthcare professionals, biotechnology and pharmaceutical companies, and regulatory authorities. These recommendations were developed based on a voting process involving 15 expert members, ensuring a consensus-driven approach. These findings underscore the importance of collaborative efforts among various stakeholders in enhancing the clinical utility of MRD testing. This project aimed to foster consensus and provide clear guidelines to support the advancement of precision medicine in oncology and improve patient outcomes in the context of perioperative care.

Background: Clinical trials have reported the efficacy of immune checkpoint inhibitors in the treatment of mismatch repair-deficient (dMMR) advanced solid tumors. The accumulated evidence of tumor agnostic agent has been made since PD-1 inhibitor was approved and used in clinical practice. Therefore, we have revised the guideline “Japan Society of Clinical Oncology provisional clinical opinion for the diagnosis and use of immunotherapy in patients with deficient DNA mismatch repair tumors, cooperated by Japanese Society of Medical Oncology, First Edition”. Methods: Clinical questions regarding medical care were formulated for patients with dMMR advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by Japan Society of Clinical Oncology (JSCO), Japanese Society of Medical Oncology (JSMO), and Japanese society of pediatric hematology/oncology (JSPHO) voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and JSPHO and the public comments among all societies’ members were done. Results: The current guideline describes two clinical questions and eight recommendations for whom, when, and how MMR status should be tested. Conclusion: In this guideline, the committee proposed eight recommendations for performing MMR testing properly to select patients who are likely to benefit from immunotherapy.

The development of novel antitumor agents and accompanying biomarkers has improved survival across several tumor types. Previously, we developed recommendations for tumor-agnostic treatments in patients with solid tumors with DNA mismatch repair deficient or neurotrophic receptor tyrosine kinase fusions. Recently, immune checkpoint inhibitors have shown efficacy in patient with tumor mutation burden-high (TMB-H) solid tumors and have been established as a third tumor-agnostic agent, making it necessary to develop the guideline prioritized for these patients. Clinical questions regarding medical care were formulated for patients with TMB-H advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by Japan Society of Clinical Oncology (JSCO), Japanese Society of Medical Oncology (JSMO), and Japanese society of pediatric hematology/oncology (JSPHO) voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and JSPHO, and the public comments among all societies' members was done. The current guideline describes three clinical questions and seven recommendations for whom, when, and how TMB should be tested, and what is recommended for patients with TMB-H advanced solid tumors. In this guideline, the committee proposed seven recommendations for performing TMB testing properly to select patients who are likely to benefit from immunotherapy.

Background: Clinical trials have reported the efficacy of tropomyosin receptor kinase (TRK) inhibitors against neurotrophic receptor tyrosine kinase (NTRK) fusion gene-positive advanced solid tumors. The accumulated evidence of tumor-agnostic agent has made since TRK inhibitors were approved and used in clinical practice. Therefore, we have revised the ‘Japan Society of Clinical Oncology (JSCO)/Japanese Society of Medical Oncology (JSMO)-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors, cooperated by the Japanese Society of Pediatric Hematology/Oncology (JSPHO)’. Methods: Clinical questions regarding medical care were formulated for patients with NTRK fusion-positive advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by JSCO, JSMO, and JSPHO voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and JSPHO, and the public comments among all societies' members was done. Results: The current guideline describes 3 clinical questions and 14 recommendations for whom, when, and how NTRK fusion should be tested, and what is recommended for patients with NTRK fusion-positive advanced solid tumors. Conclusion: The committee proposed 14 recommendations for performing NTRK testing properly to select patients who are likely to benefit from TRK inhibitors.

A recent study of the compact elliptical galaxy NGC 4486B using JWST-NIRSpec IFU kinematics confirmed a supermassive black hole (SMBH) of mass $M_{BH}=3.6\pm0.7\times10^8$ (~8% of the stellar mass). In addition to its double nucleus, the nuclear kinematics show pronounced asymmetries: a velocity-dispersion peak displaced by 6 pc from the galaxy center and a ~16 km/s offset in the mean stellar line-of-sight velocity near the SMBH. We examine the origin of the 12 pc double nucleus and these asymmetries and show that the observations favor an SMBH surrounded by an eccentric nuclear disk (END). END formation models require the SMBH to experience a gravitational wave (GW) recoil following a binary SMBH merger. Our orbit-superposition models contain ~50% retrograde stars at the edge of the nuclear region, in striking agreement with END-formation simulations. We infer a pre-merger mass ratio q>0.15 and a recoil kick of ~340 km/s. Our N-body simulations show that with such a kick, the SMBH returns to the center within ~30 Myr. Its flat central core is also consistent with earlier binary black hole scouring. We test two alternative mechanisms-buoyancy-driven oscillations and a pre-merger SMBH binary-but neither reproduces the observed offsets, favoring the GW-kick scenario. Our direct N-body simulations further show that a prograde SMBH binary in a rotating host can stall in a corotation resonance, delaying coalescence. Thus, although NGC 4486B is an old, relaxed galaxy near the Virgo cluster center, its SMBH appears to have merged only recently, making its nucleus a rare nearby laboratory for studying post-merger SMBH dynamics.

6 Background: KEYNOTE-177 (NCT02563002) evaluated the antitumor activity of pembrolizumab (pembro) vs chemotherapy ± bevacizumab or cetuximab (chemo) as first-line therapy for patients with microsatellite-instability high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). We present results of the final PFS analysis and analysis of PFS2. Methods: Patients with locally-determined MSI-H/dMMR mCRC and ECOG PS 0 or 1 were randomized 1:1 to first-line pembro 200 mg Q3W for up to 2 years or investigator’s choice of mFOLFOX6 or FOLFIRI Q2W ± bevacizumab or cetuximab (chosen before randomization). Treatment continued until progression, unacceptable toxicity, patient/investigator decision to withdraw, or completion of 35 cycles (pembro only). Patients receiving chemo could crossover to pembro for up to 35 cycles after confirmed PD. Primary end points were PFS (RECIST v1.1, central review) and OS. Secondary end points included ORR (RECIST v1.1, central review) and safety. Exploratory endpoints included duration of response (DOR), PFS2 (time from randomization to progression on next line of therapy or any cause death), and health-related quality of life (HRQoL). Data cutoff was Feb 19, 2020. Results: At data cutoff a total of 307 patients were randomized (153 to pembro, 154 to chemo). Median (range) study follow-up was 32.4 mo (24.0-48.3). Pembro was superior to chemo for PFS (median 16.5 mo vs 8.2 mo; HR 0.60; 95% CI, 0.45-0.80; P= 0.0002). The 12- and 24-mo PFS rates were 55.3% and 48.3% with pembro vs 37.3% and 18.6% with chemo. Confirmed ORR was 43.8% vs 33.1%; median (range) DOR was not reached (2.3+ to 41.4+) with pembro vs 10.6 mo (2.8 to 37.5+) with chemo. PFS2 was longer with pembro vs chemo (median not reached vs 23.5 mo [HR 0.63; 95% CI, 0.45-0.88]). OS analysis is ongoing. Grade ≥3 treatment related adverse event (TRAE) rates were 22% vs 66% for pembro vs chemo. There were no grade 5 TRAEs in the pembro arm and 1 grade 5 intestinal perforation in the chemo arm. HRQoL scores were improved with pembro vs chemo. Conclusions: Pembro provided a statistically significant improvement in PFS vs chemo as first-line therapy for patients with MSI-H/dMMR mCRC, with fewer TRAEs observed. Furthermore, pembro provided a clinically meaningful improvement in PFS2 for patients with MSI-H/dMMR mCRC. Clinical trial information: NCT02563002.

Claudin 18.2 (CLDN18.2), a tight junction protein isoform, is an emerging therapeutic target in oncology. CLDN18 is well-characterized in gastric cancer, but its pan-cancer expression profiles and isoform distributions are poorly documented. In the present study, we analyzed CLDN18 expression in patients with solid tumors enrolled in the MONSTAR-SCREEN-2 study using immunohistochemistry (IHC, n = 349) and whole-transcriptome sequencing (WTS, n = 2191). A splice junction analysis algorithm characterized isoform distribution patterns in WTS data and evaluated temporal changes using paired pre- and postchemotherapy specimens. IHC detected CLDN18.2 (≥ 40% of tumor cells showing any staining intensity) in 16.3% of patients, with highest prevalence in gastric (54.5%), biliary tract (21.7%), pancreatic (20.7%), and small intestinal (18.2%) cancers. WTS and IHC findings were significantly correlated (p < 0.001). WTS analysis with optimized transcript thresholds (n = 2191) demonstrated the CLDN18-high population to be 13.8%, with highest proportions in gastric (64.5%), small intestinal (40.0%), pancreatic (37.8%), and biliary tract (20.0%) cancers. Isoform analysis of 364 patients revealed CLDN18.2 predominance (mean 18.2/18.1 proportion 0.945), with CLDN18.1 predominance observed in only 4.9% of patients. Longitudinal analysis of 27 paired gastric cancer samples revealed a significant reduction in CLDN18 expression and a nonsignificant decrease in the CLDN18.2 proportion following chemotherapy. This analysis validates WTS as a complementary approach to IHC for CLDN18 assessment and demonstrates significant CLDN18 expression across multiple cancer types. The predominance of CLDN18.2 supports the expansion of targeted therapeutic approaches beyond gastric cancer and indicates the potential of RNA-based screening.

Introduction: No standard procedure has been established for laparoendoscopic single-site surgery for urachal remnants (LESS-U). This study aimed to report the novel surgical techniques and initial outcomes of laparoendoscopic single-site surgery with an extraperitoneal approach through a suprapubic port for urachal remnants (spLESS). Methods: Fifty-five patients (median age, 27 years; range, 15–69 years) who underwent LESS-U were analyzed. To overcome the limitations inherent in the conventional procedure (LESS-U through an umbilical port: uLESS), we modified the port placement and approached via the extraperitoneal space. spLESS is a novel procedure which reduces intestinal damage caused by the extraperitoneal approach and overcomes incomplete resection of the urachal remnant, especially in the bladder dome. Three trocars are inserted into the extraperitoneal space through a suprapubic port in spLESS, and complete resection of the urachal remnant from the umbilicus to the bladder is performed with an appropriate incision line. Patient characteristics and perioperative results were retrospectively collected. Cosmetic outcomes were prospectively evaluated using self-administered questionnaires (body image and photo-series questionnaire). Results: spLESS and uLESS were performed in 43 and 12 patients, respectively. No differences were observed between the perioperative results. The cosmetic outcomes were compared between the groups using body image and photo-series questionnaires. No patient developed major complications; there was no recurrence in either group. Conclusions: spLESS is a novel procedure which can completely resect the urachal remnant and reduce the risk of intestinal damage. spLESS is a safe, effective, and feasible procedure with high postoperative cosmesis.

[Background] The severity of oxaliplatin (L-OHP)-induced peripheral sensory neuropathy (PSN) exhibits substantial interpatient variability, and some patients suffer from long-term, persisting PSN. To identify single-nucleotide polymorphisms (SNPs) predicting L-OHP-induced PSN using a genome-wide association study (GWAS) approach. [Patients and methods] A large prospective GWAS including 1379 patients with stage II/III colon cancer who received L-OHP-based adjuvant chemotherapy (mFOLFOX6/CAPOX) under the phase II (JOIN/JFMC41) or the phase III (ACHIVE/JFMC47) trial. Firstly, GWAS comparison of worst grade PSN (grade 0/1 versus 2/3) was carried out. Next, to minimize the impact of ambiguity in PSN grading, extreme PSN phenotypes were selected and analyzed by GWAS. SNPs that could predict time to recovery from PSN were also evaluated. In addition, SNPs associated with L-OHP-induced allergic reactions (AR) and time to disease recurrence were explored. [Results] No SNPs exceeded the genome-wide significance (P < 5.0 × 10−8) in either GWAS comparison of worst grade PSN, extreme PSN phenotypes, or time to recovery from PSN. An association study focusing on AR or time to disease recurrence also failed to reveal any significant SNPs. [Conclusion] Our results highlight the challenges of utilizing SNPs for predicting susceptibility to L-OHP-induced PSN in daily clinical practice.

The treatment landscape for patients affected by gastric and colorectal cancer (G&CRC) has significantly broadened over the past decade. Molecular diagnostic methods have improved with a precision oncology-driven approach to the development of treatment options tailored to specific molecular targets, including the human epidermal growth factor 2 (HER2). While scientific evidence on the role of HER2 in G&CRC has improved, there has been a lag in general understanding and applications of testing for HER2+ G&CRC and resulting targeting treatment in the wider oncology community. To better understand and address the root causes of this gap, a needs assessment deployed among 85 oncology care providers was conducted and informed the development of an accredited online educational program entitled “GetSMART.” The program consisted of four modules developed and narrated by experts in gastrointestinal oncology. The educational content and assessment metrics were guided by a confidence-based assessment (CBA) model and the Moore, Green, and Gallis outcomes framework. Assessment methods consisted of quantitative pre- and post-activity tests, an evaluation embedded within the education (n = 163), and semi-structured interviews (n = 5) post-activity completion. Findings indicated that “GetSMART” enhanced participants’ knowledge, confidence, and intent to change practice in relation to their (1) identification of HER2 aberrations, (2) selection of appropriate treatments for HER2+ G&CRC, and (3) ability to engage patients in shared decision-making and management of adverse events. “GetSMART” can therefore be a valuable educational resource for oncology HCPs caring for patients affected by HER2+ metastatic G&CRC, offering strategies to ensure an optimal team and patient-centered approach to the care being delivered.

We reexamine the concept of the attractive gravity probe surface recently proposed as an indicator for strength of gravity. Then, we propose three new variant concepts and show refined inequalities for the four types of the AGPSs by taking account of the angular momentum, gravitational waves and matters.