搜索结果：Japanese journal of clinical oncology

Bispecific antibodies (BsAbs) that bind two distinct antigenic epitopes represent a new therapeutic paradigm. However, their clinical benefits and global regulatory status remain uncertain. In this cross-sectional analysis, BsAbs data from the US Food and Drug Administration (FDA), European Medicines Agency (EMA), Chinese National Medical Products Administration (NMPA), and Japanese Pharmaceuticals and Medical Devices Agency (PMDA) were identified up to December 31, 2025. BsAb indications, supporting trials (pivotal and confirmatory), and regulatory approval statuses were analyzed. Clinical benefits based on improved efficacy endpoints, and approval time lags among agencies, were compared. Twenty BsAbs and 33 BsAb indications were identified. Of 33 indications, 27 were oncology and six were non-oncology. Among oncology indications, only six (6/27, 22.2%) demonstrated benefits with improvements in overall survival (OS) and/or quality of life (QoL). The remaining 21 (21/27, 77.8%) oncology BsAb indications showed benefits based on surrogate endpoints. All six non-oncology indications showed benefits based on true endpoints without surrogacy. Among the 38 supporting trials for oncology indications, the majority (36/38, 94.7%) were pivotal trials, while only two (2/38, 5.3%) were confirmatory trials. Most of these trials (32/38, 84.2%) recruited relapsed/refractory patients. Of 20 BsAbs, 12 received initial approval from the FDA, five from EMA, two from NMPA, and one from PMDA. FDA-approved BsAbs obtained EMA approvals with a median lag of 82.5 days, whereas approvals in China and Japan were delayed by a median of 602 and 455 days, respectively. Most oncology BsAb indications remain without OS or QoL benefits. The FDA approved the largest number of BsAbs. Regulatory approval time lags in NMPA and PMDA are substantially longer than those in EMA.

The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.

Skeletal metastasis of unknown primary at the initial visit represents a clinically important subset of metastatic bone tumours, accounting for ~7.8%-21.7% of all skeletal metastases. This condition differs from cancer of unknown primary (CUP), in which the primary site remains unidentified after comprehensive evaluation. At this diagnostic entry point, before completion of a full work-up, early stratification is essential; however, the clinical utility of serum tumour markers at this stage remains unclear. We retrospectively reviewed 79 patients who presented with skeletal metastasis of unknown primary at the initial visit before diagnostic work-up between January 2010 and October 2023. Clinical characteristics, final primary diagnoses, types of tumour markers measured, positivity rates, and diagnostic performance were analysed. Haematologic malignancies were the most frequent final diagnoses (40.5%), followed by lung (22.8%) and prostate cancer (10.1%). A total of 17 tumour markers were measured (mean, 6.3 per patient; range, 0-12). Prostate-specific antigen (PSA), immunoelectrophoresis (IEP), soluble interleukin-2 receptor (sIL-2R), and thyroglobulin (Tg) showed high sensitivity and specificity for prostate cancer, multiple myeloma, malignant lymphoma, and thyroid cancer, respectively. Carcinoembryonic antigen (CEA) and cytokeratin 19 (CK19, CYFRA 21-1), although not organ-specific, were frequently positive in carcinomas and served as indicators of epithelial malignancy. Serum tumour markers can assist early diagnostic stratification at the initial presentation of skeletal metastasis before primary-site identification. A selective testing strategy focusing on sIL-2R, IEP, CEA, and CK19, with PSA added in men and Tg when clinically indicated, may improve diagnostic efficiency and provide a basis for considering a bone-metastasis-oriented diagnostic approach.

Insomnia is a common clinical symptom that significantly impairs quality of life (QOL) and it frequently occurs in cancer patients. However, the risk of insomnia in Japanese cancer patients compared with cancer-free patients has not yet been studied. This study evaluated the association between cancer diagnosis and the risk of insomnia disorder in the Japanese health insurance claims database. A population-based matched cohort study was performed comparing cancer patients with cancer-free patients. The primary outcome was the time to onset of insomnia disorder in cancer and cancer-free patients. Multivariate analyses were performed to determine hazard ratio (HR) for all patients and for each cancer type. A total of 36,230 cancer patients and 362,300 cancer-free patients were enrolled in this study. The median age was 53&#x2009;years. Among cancer patients, the time to onset of insomnia disorder was significantly shorter than that of cancer-free patients (stratified log-rank testing; p&#x2009;<&#x2009;0.001). In the multivariate analysis, the HR of cancer status (HR 3.39; 95% CI 3.28-3.49) was largest. In the subgroup analysis, the insomnia disorder risk was highest in patients with esophageal cancer, multiple cancers, gallbladder/biliary tract cancer, and bone and articular cartilage cancer. This study shows that Japanese cancer patients have a higher risk of developing insomnia disorder compared with cancer-free patients. The risk was especially high in cancer types which have a poor prognosis or impair the QOL of patients. These findings highlight the importance of assessing insomnia disorder frequently in cancer patients and providing interventions when it is needed.

Maintaining activities of daily living is of great importance for patients who have cancer, and dependency is associated with psychological distress. However, evidence for rehabilitation remains scarce in this setting. The objective of this study was to evaluate the efficacy of a structured rehabilitation program for maintaining activities of daily living among patients with terminal cancer. This multicenter randomized controlled trial across 19 Japanese inpatient hospices/palliative care units enrolled patients who had terminal cancer with an Eastern Cooperative Oncology Group performance status of 2-3, a life expectancy &#x2265;3 weeks, and no severe symptoms. Participants were randomly assigned (1:1, stratified by performance status and site) to either a 3-week structured rehabilitation program that incorporated key elements of rehabilitation for patients with terminal cancer or usual unstructured rehabilitation. The primary outcome was a change in the total modified Barthel Index from baseline to day 22. Secondary outcomes included the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 15-Palliative Care score and safety. Between July 8, 2019, and February 20, 2024, 130 patients were randomized (59 to the intervention group, 71 to the control group; 56 patients [43.0%] were women). The primary analysis included 77 participants who had complete data available. The mean change in total modified Barthel Index was -1.31 (95% confidence interval [CI], -10.89, 8.08) in the intervention group and -15.51 (95% CI, -24.02, -7.01) in the control group. The between-group difference was 14.21 (95% CI, 1.77-26.64; p&#xa0;=&#xa0;.026), exceeding the minimally clinically important difference (9.25). Patient-reported physical functioning on the European for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 15-Palliative Care instrument was also significantly higher in the intervention group than in the control group. No serious harms occurred. Structured rehabilitation maintained activities of daily living better than unstructured rehabilitation in patients with terminal cancer, supporting its integration into routine care even in the last stage of cancer.

Chemotherapy-induced peripheral neuropathy (CIPN) is a persistent and challenging adverse event of cancer treatment. This study aimed to describe current pharmacological and non-pharmacological approaches to CIPN and to examine their association with awareness of the Japanese clinical guideline (CIPN-GL2023). An online survey was distributed to healthcare professionals involved in CIPN management, including physicians, pharmacists, and nurses. Participants reported whether they recommended pharmacological and non-pharmacological interventions for prevention and treatment. Among 450 valid responses, 31% recommended pharmacological prevention, whereas 89% and 97% recommended pharmacological treatment for numbness and pain, respectively. Non-pharmacological strategies were recommended by 57% for prevention and 55% for treatment. Participants who were aware of the guideline were less likely to recommend pharmacological prevention and more likely to implement non-pharmacological prevention and treatment. Duloxetine, pregabalin, and mirogabalin (gabapentinoids) were commonly recommended across prevention and treatment. Guideline awareness was significantly associated with the recommendation of duloxetine for pain (65% vs. 44%, P&#xa0;<&#xa0;.01). Exercise and cryotherapy were frequently recommended for prevention, and exercise was the predominant non-pharmacological treatment. Exercise for prevention was more common as a first-line approach among guideline-aware respondents (56% vs. 35%, P&#xa0;=&#xa0;.02). Pharmacists demonstrated significantly higher guideline awareness, while nurses more frequently adopted non-pharmacological therapies. Awareness of CIPN-GL2023 was associated with increased evidence-based practice, particularly through the use of duloxetine for pain and exercise for prevention. Multidisciplinary engagement and targeted efforts to reduce non-recommended practices remain important for improving CIPN management.

In the era of immuno-oncology (IO) combination therapy, prognostic tools for elderly patients with metastatic clear cell renal cell carcinoma (ccRCC) are lacking. This study aimed to identify prognostic factors in elderly patients and evaluate a novel risk model using the restricted mean survival time (RMST) and a decision curve analysis (DCA). We retrospectively analyzed 203 patients aged &#x2265;70&#xa0;years with metastatic ccRCC treated with first-line IO combination therapy. Independent prognostic factors for overall survival (OS) were identified. Beyond the hazard ratio, a RMST analysis with a 24-month truncation time quantified absolute survival differences between risk groups. Clinical utility was evaluated using DCA. A multivariable analysis identified low body mass index, low Karnofsky performance status, elevated lactate dehydrogenase, low serum albumin, and liver metastases as independent prognostic factors. In the RMST analysis at 24&#xa0;months, significant survival disparities were quantified. The intermediate- and poor-risk groups showed mean survival reductions of 1.92 and 6.27&#xa0;months, respectively, from OS in the favorable-risk group. The model demonstrated a higher net benefit through DCA than the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) classification across a wide range of threshold probabilities for 24-month OS. The model's C-index (0.728) was higher than that of the IMDC classification (0.603). Our prognostic model for elderly patients provides a practical tool for clinical decision-making by visualizing time-based survival differences via RMST and demonstrating potential clinical utility in DCA.

This study aimed to verify the contouring accuracy of the artificial intelligence (AI)-based auto-segmentation software Contour+ (MVision AI Oy, Helsinki, Finland) both quantitatively and visually, and to evaluate its clinical validity for the thoracic region in Japanese patients. Ten thoracic radiotherapy cases with lung lesions were analyzed. Contour+ was used to automatically delineate both lungs, trachea, bronchus, esophagus, spinal cord, and heart. Three observers visually evaluated the auto-contours using a five-point scoring system, and the final manually corrected contours were used as the reference to calculate the dice similarity coefficient (DSC), Hausdorff distance (HD), and volume differences. In all cases, the AI auto-contours were evaluated as "clinically acceptable with minor modifications (score &#x2265;3)," with an average score of 4.4. The mean DSC values were 1.00 for the lungs, 0.99 for the trachea, 0.91 for the bronchi, 0.86 for the esophagus, 0.99 for the spinal cord, and 0.99 for the heart, indicating high agreement. The mean HD values were 5.68&#x2009;mm, 8.72&#x2009;mm, and 3.30&#x2009;mm for the bronchi, esophagus, and heart, respectively. The mean volume changes after manual correction were 4.02&#x2009;cc for the bronchi, 2.55&#x2009;cc for the esophagus, and 2.58&#x2009;cc for the heart. AI-based auto-segmentation software Contour+ demonstrated high geometric agreement and clinical validity for major thoracic organs in Japanese patients, suggesting its potential to reduce the contouring workload and promote standardization in radiotherapy treatment planning.

Postmastectomy pain syndrome (PMPS) is a prevalent chronic pain condition that occurs after breast cancer surgery, often impairing quality of life in survivors of breast cancer. Despite its prevalence, no standardized treatment has been established. Acupuncture has been reported to be an efficacious intervention for the management of chronic pain and may be an effective treatment for PMPS. This study aims to explore the effectiveness and safety of integrative treatment of acupuncture-based intervention for PMPS. This is a single-center, single-arm, prospective interventional study. Eligible participants are patients with breast cancer who experience chronic postoperative pain in the chest, neck, or shoulder with a numerical rating scale (NRS) score &#x2265;4, are at least 6 months postcurative treatment, have no evidence of disease recurrence, and are not receiving anticancer treatment at enrollment. Participants will receive the intervention once weekly for 12 sessions, followed by a 4-week observation period. The primary end point is the change in the average pain NRS score from baseline to week 16. The study commenced in October 2023 and is scheduled to continue through March 31, 2027. The first participant was enrolled on October 24, 2023. As of the manuscript submission, 24 patients have been enrolled. This study will explore the potential role of an integrative treatment of acupuncture-based intervention in the management of PMPS. The results will contribute to the evidence base for acupuncture in PMPS and inform the design of future clinical studies.

To define the time course of fracture risk with radium-223 in combination with androgen receptor pathway inhibitor (ARPi) therapy and assess the clinical impact of concomitant bone-protective agent (BPA) use on mitigating this risk. An exploratory person-time approximation approach was used to perform a Bayesian re-analysis of the landmark ERA223 and PEACE-3 clinical trials. In ERA223, we estimated interval-specific fracture incidence rate ratios (IRRs) during follow-up to characterize temporal trajectories. Interval-specific analyses were based on an exploratory person-time approximation approach. In PEACE-3, we used published hazard ratios to re-derive posterior distributions of risk ratios, risk differences, and posterior distributions comparing pre- vs post-mandatory BPA fracture incidences. Posterior distributions were modeled with beta-binomial and gamma-Poisson conjugate priors. In the ERA223 population, the fracture excess risk peaked during the first year of treatment, with elevated interval-specific IRRs in the 0-6&#xa0;month and 6-12&#xa0;month intervals. In PEACE-3, the treatment-induced fracture burden for the radium-223 combination treatments was lower following requirement of BPA, with the risk ratio (RR) falling from 2.54 (95% credible interval [CrI]&#xa0;=&#xa0;1.53-4.60) prior to the mandate to 1.46 (95% CrI 0.88-2.49) post-implementation. The addition of BPA prophylaxis demonstrated a synergistic protective effect, yielding a more pronounced reduction in fracture risk within the radium-223 combination arm relative to the ARPi-monotherapy group. Fracture risk was confined to early periods of ERA223 treatment and diminished after the compulsory addition of BPAs in PEACE-3. Due to the limitations of using estimated person-time data and observational comparisons, the findings are best interpreted as descriptive and hypothesis-generating.

Transverse colon cancer is traditionally treated with extended right hemicolectomy (EHC), which involves division of the middle colic, right colic, and ileocolic arteries, along with removal of the terminal ileum and right colon. Transverse colectomy (TC) is a limited resection removing only 10&#xa0;cm of bowel on either side of the tumor, along with resection of the middle colic artery and regional lymphadenectomy. This approach may contribute to the preservation of bowel function without compromising oncologic adequacy. This multicenter, randomized, phase III trial is designed to evaluate the non-inferiority of TC compared with EHC in terms of relapse-free survival among patients with Stage II/III transverse colon cancer whose main feeding artery is the middle colic artery. In total, 510 patients will be enrolled across major Japanese centers over 5&#xa0;years. The trial has been registered with the Japan Registry of Clinical Trials (jRCT1030240479).

Spontaneous tumor lysis syndrome (STLS) is rare in solid tumors but highly lethal. Older adults may be especially vulnerable due to comorbidity and homeostenosis. Our objective was to synthesize reported cases among older adults with solid tumors and describe clinical features, prognostic factors, and outcomes. We systematically reviewed reports of patients &#x2265;65&#xa0;years with STLS from solid tumors, excluding hematologic malignancies or recent cytotoxic therapy. PubMed and Embase were searched through 16 September 2025, plus one hand-identified case. Data extracted included demographics, tumor type, metastatic activity, laboratory results, renal failure, and mortality. Hypothesis-generating analysis included Fisher's exact, Mann-Whitney U tests, and the area under the curve (AUC) with a Youden's J-derived cutoff (to summarize phosphate's discrimination for death). Eighteen publications (20 patients) met criteria; no Japanese cases, highlighting a potential regional data gap. Overall mortality was 74%. Renal failure (14 of 20) strongly predicted death (13/14 vs 0/4, P&#xa0;<&#xa0;.002). Phosphate was higher in non-survivors (median 7.1 vs 5.25&#xa0;mg/dL; P&#xa0;=&#xa0;.040) and discriminated death well (AUC&#xa0;=&#xa0;0.865); a Youden-optimal phosphate threshold &#x2248;6.0&#xa0;mg/dL signaled high mortality risk. Tumors were almost exclusively metastatic; 88% involved the liver. Although rare, with evidence limited to case reports inherently at high risk for publication bias and imprecision, STLS is almost exclusively associated with metastatic disease, usually with hepatic involvement. It is lethal, particularly when accompanied by renal failure and/or hyperphosphatemia (>6&#xa0;mg/dL) in older adults with solid tumors. Early recognition and management are critical.

Cabozantinib treatment is associated with improved survival in renal cell carcinoma (RCC) patients with bone metastasis. We evaluated the direct effects of cabozantinib on bone metastasis in advanced RCC (aRCC). In this multicenter, open-label study, adult Japanese aRCC patients with bone metastasis received oral cabozantinib 60&#x2009;mg once daily until drug discontinuation/data cut-off. The primary endpoint was the objective response rate (ORR) of bone target lesions (modified MD Anderson criteria) evaluated by an independent radiology committee. Secondary endpoints were overall survival (OS), disease control rate (DCR) of bone lesions, progression-free survival (PFS), symptomatic skeletal events (SSEs), bone-specific PFS, and safety. Exploratory endpoints were changes in bone turnover, plasma biomarkers, and health-related quality of life (HRQoL). Thirty-one patients were enrolled (median age, 70.0&#x2009;years; 64.5% men). The ORR of bone target lesions was 6.5% (90% CI 1.2-18.9), DCR was 90.3% (90% CI 76.8-97.3), and the median change in bone target lesion size was -5.2% (range-42.8 to 19.2). Median PFS was 11.9&#x2009;months (95% CI 5.7-not evaluable), median OS was 24.9&#x2009;months (95% CI 19.1-not evaluable), and three patients reported SSEs. Bone-specific PFS remained >&#x2009;60% among patients who were evaluable during follow-up. Levels of bone-turnover markers generally decreased; no trends were observed in plasma biomarkers. EQ-5D-5L index values remained generally stable. Common adverse events were palmar-plantar erythrodysesthesia syndrome (54.8%), malaise (45.2%), diarrhea, abnormal hepatic function (32.3%), and hypertension (32.3%). Most aRCC patients showed favorable disease control following cabozantinib treatment. No new safety issues were observed. Japan Registry of Clinical Trials (JRCT), registration no. jRCTs031210220.

Lung squamous cell carcinoma (LUSC) lacks well-defined molecular targets. This study investigated the clinical and biological relevance of POU class 2 homeobox 3 (POU2F3), a tuft cell-associated transcription factor, in LUSC. RNA sequencing data of patients with LUSC from The Cancer Genome Atlas (TCGA cohort, n&#xa0;=&#xa0;190) was analysed and compared to a cohort of surgically resected cases analyzed via immunohistochemistry (IHC cohort, n&#xa0;=&#xa0;137). Prognostic impact was assessed via survival analyses. Transcriptomic features, pathway enrichment, and immune profiles were evaluated via differentially expressed gene analysis, Gene Set Enrichment Analysis, and CIBERSORTx. High POU2F3 expression independently predicted poor overall survival in the TCGA cohort (HR&#xa0;=&#xa0;2.06, 95% CI: 1.04-4.08, P&#xa0;=&#xa0;0.039). In contrast, POU2F3 expression was not prognostic in the IHC cohort (P&#xa0;=&#xa0;0.995). Morphologically, POU2F3-positive tumours were enriched for non-keratinizing and poorly differentiated subtypes. Transcriptomic analysis showed suppression of proliferation and immune-related pathways (FDR&#xa0;<&#xa0;0.001), with suggestive enrichment of the TGF-&#x3b2; (FDR&#xa0;=&#xa0;0.143) and p53 (FDR&#xa0;=&#xa0;0.229) signaling pathways. On immune deconvolution, POU2F3-high tumours showed a nominal increase in activated dendritic cells, which did not withstand multiple testing correction. POU2F3 protein was detected in 12.4% of tumours and was significantly associated with p53 or RB1 abnormalities (single or double) (P&#xa0;=&#xa0;0.028). POU2F3 marks a transcriptionally distinct, early-stage subtype of LUSC with keratinization-related features. Its prognostic relevance appears context-dependent and requires prospective validation in uniformly treated cohorts.

Cancer is characterized not only by malignant transformation driven by genomic alterations but also by remarkable cellular plasticity that enables adaptation to environmental and therapeutic stress. Cancer cell plasticity frequently involves extensive remodeling of gene regulatory and transcriptional networks arising from complex interactions between genetic alterations and nongenetic regulatory mechanisms. The regulatory sources of cancer cell plasticity include changes in RNA molecules, such as microRNAs, alterations in RNA processing, epigenetic reprogramming, and higher-order cellular organization. In particular, biomolecular condensates-membraneless organelles formed through phase separation-and extrachromosomal DNA (ecDNA) have gained attention as important regulators of gene expression and cellular heterogeneity in cancer. Alterations in biomolecular condensates in cancer cells are frequently associated with dysregulated gene regulation and cell signaling. In addition, ecDNA represents an emerging mechanism that mediates high-level oncogene transcription, tumor heterogeneity, and drug resistance in cancer. This review summarizes recent advances in understanding how biomolecular condensates and ecDNA contribute to the regulation of cancer cell plasticity and discusses their implications for tumor evolution and therapeutic resistance. We also outline the usefulness of several CRISPR-based methods to test the roles of ecDNA, including generation of ecDNA-like circular DNA as model systems, optimization of Cas9 activity for prevention of Cas9-induced ecDNA loss and efficient ecDNA knock-in, and CRISPR interference-based perturbations.

The purpose of this study was to identify implementation strategies and determine priorities for establishing a seamless cancer rehabilitation delivery system based on consensus among multidisciplinary stakeholders. An online modified-Delphi study was conducted. A total of 100 stakeholders (healthcare professionals, researchers, cancer survivors, and members of patient support groups) with experience in cancer rehabilitation were invited. Participants selected the top three barriers to cancer rehabilitation in the first survey. In the second survey, the implementation strategy list was provided, and the effectiveness of each strategy was rated using a 4-point Likert scale. In the third survey, participants evaluated the impact and cost of successful implementation using a 4-point scale to determine priority. Valid responses were obtained from 85 participants for the first survey, 64 for the second survey, and 59 for the third survey. Consensus was reached on all 35 implementation strategies as effective measures (agreement rate for each item ranged from 70.3% to 98.4%). Fourteen items were judged very effective. The assessment of priority considering impact and cost indicated that reinforcing multidisciplinary collaboration and improving access to information were high priorities. This study identified implementation strategies and priorities for cancer rehabilitation based on expert consensus. These findings demonstrate that improving inter- and intra- organizational processes is as crucial as institutional and structural enhancements. The identified strategies are expected to bridge the gap between evidence and clinical practice in Japan, contributing to the promotion of effective, continuous cancer rehabilitation delivery systems.

To compare patient characteristics and end-of-life treatment between designated cancer care hospitals and non-designated hospitals, focusing on non-designated hospitals. We used the National Database from 2013 to 2015, provided by the Ministry of Health, Labor and Welfare. We analyzed 491&#x2009;964 patients of cancer descendants (designated hospitals, 164&#x2009;063 and non-designated hospitals, 327&#x2009;901). Non-designated hospitals treated older patients, specifically aged 85&#xa0;years or older (non-designated hospitals: 26% vs designated hospitals: 11%), and fewer patients without comorbidities (32% vs 45%). Regarding end-of-life treatment in the last two weeks, non-designated hospitals had lower palliative care team fees (1% vs 11%; Relative Risk&#xa0;=&#xa0;0.14), slightly lower use of strong opioids (53% vs 65%; RR&#xa0;=&#xa0;0.81), and less use of antipsychotics (23% vs 37%; RR&#xa0;=&#xa0;0.63). Non-designated hospitals used anticancer drugs less frequently (5% vs 10%; RR&#xa0;=&#xa0;0.51), however, the use of intravenous hydration over 250&#xa0;mL/day was higher (55% vs 37%; RR&#xa0;=&#xa0;2.27). In non-designated hospitals, although ICU admission was less frequent (1% vs 5%; RR&#xa0;=&#xa0;0.27), there was no difference in cardiopulmonary resuscitation (5% vs 5%; RR&#xa0;=&#xa0;1.02). Non-designated hospitals treat more complex patients. In addition, non-designated hospitals had low palliative care team fees, low opioid and other essential drug prescriptions; however, the frequency of artificial hydration was higher. Although non-designated hospitals provided a lower frequency of end-of-life aggressive treatment, no difference was observed in life-sustaining treatments.

Ependymomas are rare pediatric brain tumors characterized by clinical and molecular heterogeneity. The JCCG EPN23 study is a nationwide prospective trial in Japan designed to evaluate outcomes of risk-adapted therapy stratified by tumor location, extent of resection, and molecular classification. Patients younger than 30&#xa0;years with pathologically confirmed ependymoma are enrolled and assigned to one of three treatment strata. Stratum 1 evaluates whether omission of radiation therapy for patients with gross total resection of supratentorial or non-PFA infratentorial tumors. Stratum 2 administers radiation therapy followed by maintenance oral etoposide for patients with minimal residual tumors or PFA subtype. Stratum 3 provides neoadjuvant chemotherapy to facilitate total resection of residual tumors. Patients younger than 1&#xa0;year and those with metastatic or extracranial disease are assigned to an observational cohort, in which no specific treatment is mandated by study protocol. Central surgical and pathological review, along with molecular and DNA methylation profiling, are conducted to improve diagnostic precision and prognostic stratification. The study prospectively evaluates the feasibility and efficacy of radiation-sparing strategies in selected patient groups and other risk-adapted treatment approaches. Outcomes including survival, disease control, and treatment-related morbidity will be analyzed according to each risk group. JCCG EPN23 aims to optimize therapeutic strategies for pediatric ependymoma by integrating molecular classification with risk-adapted treatment. The results are expected to inform future treatment protocols and improve survival while minimizing long-term morbidity.

Frailty and comorbidity substantially influence clinical outcomes in patients with multiple myeloma (MM), yet existing tools such as the IMWG frailty score and Charlson Comorbidity Index (CCI) have limitations in real-world applicability and disease specificity. To develop and externally validate a multiple myeloma-specific comorbidity index (MM-CI) using real-world data from Korean and Japanese cohorts. This retrospective study was conducted in two parts: (I) development of MM-CI using a nationwide Korean claims cohort of 17,273 MM patients diagnosed between 2007 and 2022; and (II) external validation using two independent multicenter registry cohorts: 1473 Korean patients (2010-2021) and 314 Japanese patients (2008-2023). Multivariable Cox regression was performed incorporating key clinical factors, including ECOG performance status, R2-ISS stage, and frontline treatment intensity. The MM-CI was derived from eight variables: male sex; age 60-69, 70-79, and &#x2265;80 years; congestive heart failure, cerebrovascular disease, hepatic disease, and cancer: 1&#x2009;&#xd7;&#x2009;(Sex: Male)&#x2009;+&#x2009;2&#x2009;&#xd7;&#x2009;(Age: 60-69 years)&#x2009;+&#x2009;4&#x2009;&#xd7;&#x2009;(Age: 70-79 years)&#x2009;+&#x2009;6&#x2009;&#xd7;&#x2009;(Age &#x2265;80 years)&#x2009;+&#x2009;2&#x2009;&#xd7;&#x2009;(Congestive heart failure: Yes)&#x2009;+&#x2009;1&#x2009;&#xd7;&#x2009;(Cerebrovascular disease: Yes)&#x2009;+&#x2009;1&#x2009;&#xd7;&#x2009;(Hepatic disease: Yes)&#x2009;+&#x2009;1&#x2009;&#xd7;&#x2009;(Cancer: Yes). Risk scores stratified patients into four groups: low (0-2), intermediate-I (3-4), intermediate-II (5), and high (&#x2265;6), with corresponding median overall survival (OS) of 72.5, 43.8, 30.9, and 20.3 months, respectively. Validation analyses demonstrated superior predictive performance of the MM-CI (AUC: 0.637) compared to the conventional age-adjusted CCI (AUC: 0.613) and the concise CCI used in the IMWG frailty score (AUC: 0.569). The MM-CI remained independently prognostic after adjustment for ECOG, R2-ISS, and treatment intensity. The MM-CI provides a simple, objective, and clinically applicable tool for comorbidity-based risk stratification in MM. It outperforms existing models and may support treatment decisions in real-world practice.