Leptomeningeal metastases (LM) from melanoma are rare and associated with dismal outcomes. Intrathecal PD-1 antibody therapy has shown encouraging activity in LM. Radiotherapy may enhance tumor immunogenicity and potentially augment immune checkpoint blockade within the central nervous system. The efficacy and safety of combining intrathecal PD-1 antibodies with whole-brain radiotherapy (WBRT) in melanoma LM remain unclear.

Multiple myeloma (MM) persists within a specialized bone marrow niche in which malignant plasma cells, immune dysfunction, inflammatory signaling, and metabolic stress reinforce one another. To resolve this ecosystem at compartment-level resolution, we integrated public single-cell RNA sequencing data with pathway scoring, cell-cell communication inference, independent clinical validation, multiplex immunofluorescence, and metabolic perturbation experiments. Analysis of 95,940 bone marrow cells identified 32 annotated populations and revealed broad microenvironmental remodeling in MM, including plasma-cell expansion, altered cytotoxic and dendritic-cell compartments, TAM-associated inflammatory programs, and lineage-specific hematopoietic perturbations. Hallmark pathway analysis identified recurrent immunometabolic programs, including IL6-JAK-STAT3, TNFα-NFκB, mTORC1 signaling, oxidative phosphorylation, unfolded protein response, hypoxia, and checkpoint/exhaustion-associated pathways. CellChat analysis showed disease-associated rewiring of ligand-receptor networks involving malignant plasma cells, TAMs, dendritic cells, and T/NK subsets, with checkpoint-enriched communication and clinically relevant plasma-cell and CD274 survival associations. Serum IL-6 was elevated in an independent clinical validation cohort. Multiplex immunofluorescence confirmed PD-L1-positive plasma cells, C1QA/C1QB/C1QC-positive TAMs expressing LAG3, and CD8-positive/LAG3-positive cytotoxic T cells. Mechanistically, malignant plasma cells showed transcriptional activation of LDH-associated glycolytic/lactate programs and ASCT2/SLC1A5-GLS-linked glutamine-metabolic programs, nominating these pathways as functional vulnerabilities. Accordingly, the LDH inhibitor galloflavin and the ASCT2/SLC1A5 glutamine-transport inhibitor V-9302 suppressed RPMI-8226 viability in dose- and time-dependent manners; their combination produced synergistic anti-myeloma activity supported by Bliss synergy, combination-index analysis, observed-versus-expected inhibition, and apoptosis-related validation. Together, these findings support an IL6-centered immunometabolic communication circuit linking malignant plasma cells, TAMs, and dysfunctional T cells, and identify cooperative glycolytic/lactate and glutamine-dependent metabolic vulnerabilities with therapeutic relevance in MM.

To develop and validate a pretreatment computed tomography (CT)-derived model for predicting major pathological response (MPR) to neoadjuvant immunochemotherapy in resectable non-small-cell lung cancer (NSCLC).

Thyroid dysfunction is among the most frequent endocrine immune-related adverse events (irAEs) during PD-1/PD-L1 blockade, but whether baseline thyroid function and treatment-emergent thyroid dysfunction (TeTD) predict pathological response and survival after neoadjuvant immunochemotherapy in locally advanced gastric or gastroesophageal junction adenocarcinoma (LAGC/GEJC) remains unclear.

Due to the rarity of Waldenstrom macroglobulinemia (WM) and scarcity of direct comparative data, there remains uncertainty regarding the optimal therapeutic approach for treatment-naïve patients and subsequent treatment sequence. To bridge such knowledge gap and generate data on most appropriate treatment in relatively resource constraint setting, we conducted this study with 168 WM patients.

In August 2017, Republic of Korea (South Korea) expanded its national hospice and palliative care program to cover several serious non-cancer illnesses, including liver cirrhosis (LC). We aimed to examine the access of palliative care services among adults who died of LC compared with those who died of hepatocellular carcinoma (HCC).

Diagnosis and management of cervical cancer require multiple investigations and specialist reviews, with delays leading to increased mortality and morbidity. Australia's Optimal Care Pathways (OCPs) recommends that patients with suspected diagnosis of cervical cancer should have their diagnostic processes completed within certain timeframes. Despite these guidelines, there is currently no benchmarking of cervical cancer timelines.

To evaluate the 2-year nodule volume reduction rate (VRR), recurrence rate, and safety of ultrasound-guided microwave ablation (MWA) for benign thyroid nodules with different compositions, and to identify independent risk factors affecting therapeutic outcomes.

RAS mutations occur in patients with several types of vascular anomalies, but effective treatments remain limited. To address this need, we evaluated the RAS (ON) multi-selective inhibitor RMC-7977 in human endothelial cells (ECs) expressing the NRASQ61R mutation found in kaposiform lymphangiomatosis (KLA). RMC-7977 was evaluated using in vitro and in vivo models. Doxycycline-inducible NRASWT and NRASQ61R human ECs were treated with RMC-7977 (3.12-100 nM) or vehicle. We assessed signalling pathways, proliferation, migration, morphology, and angiopoietin-2 (ANG-2) production. NRASQ61R ECs in a 3D angiogenesis assay were also treated with RMC-7977. For in vivo studies, NRASQ61R ECs were injected into flanks of nude mice on a doxycycline diet to generate xenografts. Mice received oral RMC-7977 or vehicle, and xenografts were collected after 11 days. RMC-7977 inhibited NRASQ61R-induced ERK phosphorylation and reduced proliferation, migration, spindle-like morphology, and ANG-2 production in a dose-dependent manner. RMC-7977 reduced vascular area in the angiogenesis assay. In vivo, RMC-7977 reduced xenograft weight, vascular area, and p-ERK staining. Overall, RMC-7977 suppressed NRASQ61R-mediated signalling, aberrant EC behaviour, and ANG-2 production in vitro and reduced vascular overgrowth in angiogenesis assays and mouse xenografts. Therefore, RMC-7977 may be a promising therapeutic candidate for RAS-driven vascular anomalies, including KLA.

Oligoprogression in prostate cancer is increasingly recognized as a clinically meaningful state with increased incidence due to effective systemic therapies and more sensitive molecular imaging, particularly prostate-specific membrane antigen positron emission tomography (PET). Broadly, oligoprogressive prostate cancer is defined as progression at a limited number of metastatic sites, commonly three to five or fewer, while the remainder of disease remains stable on ongoing therapy. In prostate cancer, however, this concept spans biologically and clinically distinct states, including repeat oligorecurrence off systemic therapy, new oligometastasis at the time of castration-resistance, and oligoprogression in castration-resistant disease. These differences are important because the goals of metastasis-directed therapy (MDT) differ across settings. In castration-sensitive disease, local therapy is often used to delay initiation or re-initiation of androgen deprivation therapy (ADT) and preserve quality of life. In castration-resistant disease, the goal is more often to ablate resistant clones, prolong the benefit of otherwise effective systemic therapy, and defer next-line treatment. Prospective randomized phase II data in oligometastatic castration-sensitive prostate cancer (CSPC) support MDT as an ADT-sparing strategy, and emerging studies suggest that repeat courses of stereotactic body radiotherapy (SBRT) may remain feasible in selected patients with serial limited-site recurrence. In metastatic castration-resistant prostate cancer (mCRPC), two randomized phase II trials and multiple prospective and retrospective series support the addition of MDT in carefully selected men. Across both disease states, local control rates are high and grade 3 or higher toxicity is uncommon. Nevertheless, major questions remain regarding optimal patient selection, imaging definitions, integration with systemic intensification, and the role of biomarkers in distinguishing durable oligoprogression from impending polyprogression. This review summarizes the biologic rationale, clinical evidence, and future directions for MDT in oligoprogressive prostate cancer.

The management of metastatic cancer is shifting from a strict division between curative local therapy and palliative systemic treatment toward a biology-driven continuum. In this setting, stereotactic body radiotherapy (SBRT), or stereotactic ablative radiotherapy (SABR), has emerged as an effective consolidative approach for patients with limited metastatic burden. Its role is now being explored beyond the classical oligometastatic paradigm, including oligoprogressive and selected polymetastatic disease. This narrative review summarizes the evidence supporting SBRT/SABR in patients with metastatic burden exceeding the traditional definition (≤3-5 metastases), focusing on emerging clinical scenarios.

Thrombocytopenia is a common toxicity of oxaliplatin-based chemotherapy and may be linked to hepatic sinusoidal obstruction and splenic enlargement. In the TORCH trial, adding PD-1 blockade to an oxaliplatin-containing total neoadjuvant therapy (TNT) regimen improved tumor response in patients with locally advanced rectal cancer (LARC), but thrombocytopenia appeared more frequent and more severe. Here, we evaluated whether adding PD-1 blockade to TNT increased thrombocytopenia risk and explored its association with hepatic injury and splenomegaly.

Prostate biopsy remains essential for the diagnosis of prostate cancer. Although the transperineal approach is increasingly favored, transrectal prostate biopsy (TRPB) continues to be performed in many institutions. In our institution, single-dose flomoxef (FMOX) was introduced as a prophylactic antibiotic in response to increasing resistance to levofloxacin (LVFX). This study evaluated the effectiveness and microbiological validity of FMOX using real-world clinical data.

We aimed to evaluate the prognostic utility of subclassifying patients with intermediate-risk prostate cancer into favorable and unfavorable subgroups in a large Japanese cohort undergoing radical prostatectomy, focusing on adverse pathology and oncologic outcomes.

Colorectal cancer (CRC) is a heterogeneous disease shaped by genetic and epigenetic alterations. Approximately 20% of CRCs exhibit widespread CpG island hypermethylation, termed the CpG Island Methylator Phenotype (CIMP), frequently accompanied by MLH1 promoter hypermethylation, deficient mismatch repair (dMMR) and microsatellite instability (MSI). However, methylation patterns associated with MSI, independent of CIMP and MLH1 silencing, and the influence of anatomical location and patient age on the CRC methylome remain incompletely defined. We performed epigenome-wide DNA methylation profiling of 259 sporadic CRCs using the Illumina EPICv2 array. Differential methylation between MSI and microsatellite stable (MSS) CRCs was assessed after adjustment for tumour purity and anatomical location, then MLH1 promoter methylation and CIMP status, to delineate MSI-associated methylation changes. Additionally, we evaluated the effects of anatomical location and age on methylation patterns. While differential methylation between MSS and MSI CRCs was dominated by MLH1 promoter hypermethylation, additional adjustment for MLH1 hypermethylation and CIMP identified 656 CpG sites associated with MSI, beyond the global methylator phenotype. These included hypermethylation at LRP6, GSK3β, and CDK12, identifying differential methylation of genes involved in WNT signalling and transcriptional regulation. Within MSI CRCs, we observed the co-occurrence of MLH1 hypermethylation with promoter hypermethylation at TXNRD1. Anatomical location was strongly associated with methylation, whereas age had more modest effects. These results identify methylation changes associated with sporadic MSI beyond CIMP status and MLH1 hypermethylation, reveal heterogeneity within MSI CRCs, and indicate that anatomical location is a major determinant of the CRC methylome, advancing molecular stratification of CRC.

Glioblastoma is profoundly heterogeneous, and single-modality analyses often miss prognostically relevant structure. We introduce a transparent, end-to-end workflow that fuses available whole-slide histology and RNA-seq to discover clinically meaningful glioblastoma subgroups using an unsupervised learning model after feature extraction. Haematoxylin-eosin slides are tiled, tissue-screened and stain-normalised; tiles are embedded with a pretrained ResNet-50 to yield 2048-dimensional features, averaged per patient and compressed to 30-D by an autoencoder. In parallel, RNA-seq (~48 k genes) undergoes low-variance filtering and normalisation, then a second autoencoder produces a 30-D transcriptomic embedding. The two 30-D representations are concatenated into a 60-D fused vector, robustly scaled and refined with PCA (≈98% variance retained). Across K-means, Gaussian mixture models and Agglomerative clustering (k = 2-20), Agglomerative k = 2 was decisively best (mean silhouette ≈0.53), yielding clusters of 150 and 8 patients (survival subset 147 and 8). Survival separation was substantial (median 454 vs. 138 days; log-rank p = 0.0096). In Cox models, the poorer-prognosis cluster showed increased risk (HR ≈ 2.70), which remained significant after age adjustment (HR = 2.15, 95% CI 1.04-4.46; age per year HR = 1.02, 95% CI 1.01-1.04). Attribution and consensus analyses yielded compact, interpretable gene sets (22 shared; 8 per cluster), including markers associated with NOTCH/γ-secretase and oxidative phosphorylation. These findings nominate biologically plausible hypotheses for future validation rather than immediate treatment-selection rules. Overall, this study demonstrates that auditable late fusion of histology and transcriptomics, built from routine data, can identify survival-associated glioblastoma subgroups and provides a hypothesis-generating framework for prospective, harmonised, multi-centre validation.

Population aging has substantially altered the epidemiology and management of gastric cancer, particularly in East Asia, where a growing proportion of patients with early gastric cancer (EGC) are elderly. Current Japanese guidelines define indications and curability criteria for endoscopic resection (ER) irrespective of age. Consequently, gastrectomy with lymphadenectomy remains the standard treatment for EGC that exceeds established absolute and expanded ER indications or is classified as endoscopic curability (eCura) C-2 after ER. However, given the heterogeneity of metastatic risk and patient characteristics, uniform recommendation of gastrectomy may result in overtreatment in elderly patients. Nationwide registry data on patients undergoing gastrectomy have demonstrated that overall prognosis becomes increasingly limited and postoperative mortality rises with age, especially in men aged ≥ 75 years and women aged ≥ 80 years. These findings highlight the need to reconsider ER indications and post-resection management in elderly patients based on estimated lymph node metastasis (LNM) risk, operative mortality, and life expectancy. Recent studies suggest that expanding ER indications and redefining curability criteria in elderly patients using a higher acceptable LNM risk threshold, such as 10%, may represent a rational risk-adapted strategy. This concept is currently being evaluated in the multicenter phase III confirmatory trial conducted by the Japan Clinical Oncology Group (JCOG1902). Importantly, long-term outcomes in elderly patients with EGC are influenced by non-gastric cancer deaths. Therefore, management strategies should integrate tumor-related risk with patient-related factors, including comorbidities, nutritional status, frailty, and competing mortality risks, to achieve individualized and clinically meaningful care in this expanding population.

Radical hysterectomy with pelvic lymphadenectomy has been considered the primary treatment for early-stage cervical cancer without lymph node involvement. This study aimed to evaluate recurrence rates and the prevalence of lymph node metastasis after treatment with conization combined with lymph node assessment.

Resistin is a macrophage-associated cytokine linked to obesity-driven inflammation, a recognised risk factor for colorectal cancer. Prior studies of circulating resistin in colorectal cancer have reported inconsistent findings, largely because patients were analysed as a single group without accounting for tumour stage. Whether resistin follows a stage-specific pattern across the adenoma-carcinoma sequence, independent of insulin resistance and conventional tumour markers, has not been systematically examined.

Clonal hematopoiesis (CH) arises from the expansion of hematopoietic stem and progenitor cells bearing somatic mutations, often in genes linked to epigenetic regulation and inflammation. Once considered a benign age-related phenomenon, CH has gained increasing attention for its potential to influence cancer biology beyond hematologic malignancies. Recent studies have uncovered an unexpectedly high prevalence of CH in patients with colorectal cancer (CRC), raising important questions about its origin, context-specific drivers, and pathological consequences. While cytotoxic therapies are known contributors, accumulating evidence suggests that the chronic inflammatory and metabolic alterations intrinsic to CRC may also shape hematopoietic clonality. In turn, CH-derived myeloid cells harboring mutations such as DNMT3A or TET2 can modulate the tumor microenvironment, promote inflammation, and impair antitumor immunity. In this review, we synthesize emerging findings on the bidirectional relationship between CH and CRC, highlighting the mechanistic underpinnings and potential implications for disease progression, therapeutic resistance, and immune modulation. Understanding this evolving interface may open new avenues for risk stratification and treatment personalization in CRC.