Our previous findings demonstrated the promising antitumor activity and manageable safety of sintilimab-lenvatinib conversion therapy. The current study aimed to evaluate long-term survival outcomes in patients with unresectable hepatocellular carcinoma (HCC) who underwent sequential surgical resection after successful conversion therapy. In this prospective, single-arm, expansion, phase II trial, patients with unresectable HCC received lenvatinib plus sintilimab conversion therapy. Hepatectomy was performed in consenting patients after successful conversion therapy. The primary endpoint was the conversion rate; secondary endpoints included median overall survival (OS), 5-year survival rates, and recurrence-free survival (RFS). Successful conversion was achieved in 67 of 120 patients (56%, 67/120). Independent imaging review per mRECIST and RECIST v1.1 criteria demonstrated objective response rates of 58.3% (70/120) and 45.8% (55/120), respectively. With a median follow-up of 41.0 months (95% confidence interval [CI], 39.5-42.5) for the entire cohort, the median OS was 36.0 months (95% CI, 25.0 to not estimable [NE]), with a 5-year OS rate of 42.6% (95% CI, 34.0-53.0). Following multidisciplinary team evaluation and consideration of patient preferences, 60 patients underwent surgical resection, achieving a median RFS of 40.0 months (95% CI, 24.0 to NE) and a 5-year survival rate of 73.9% (95% CI, 62.7-87.1). Grade ≥3 treatment-related adverse events occurred in 37 patients (31%). Approximately half of the patients with unresectable HCC achieved successful conversion after sintilimab plus lenvatinib therapy. Among those who achieved successful conversion, subsequent curative surgery demonstrated not only a favorable safety profile but also significant survival benefits. Trial registration number: ChiCTR1900023914.

The optimal strategy for combining radiotherapy (RT) and immunotherapy remains under intensive investigation. Here we developed TRIDENT (Triple Radio-Immunotherapy-Driven ENhanced Therapy), a novel triple-modality regimen combining immunomodulatory low-dose RT (LDRT) to large tumor(s), immunogenic high-dose RT (HDRT) to small tumor(s), and PD-1 blockade. In our phase I trial of 29 patients with treatment-naïve, PD-L1-positive advanced non-small cell lung cancer (NSCLC), TRIDENT achieved a median overall survival (mOS) of 51.3 months (95% CI, 20.7-not reached), higher than outcomes typically reported with contemporary standard (chemo)immunotherapy. This durable survival signal was corroborated in an independent real-world cohort of 97 patients with advanced lung cancer (mOS: 41.5 months; 95% CI, 26.3-63.7). Mechanistically, TRIDENT elicited neutrophil-dependent, systemic antitumor immunity and induced a distinct population of antitumor TNF-α⁺ neutrophils marked by increased MHC and costimulatory molecule expression. Neutrophil recruitment was driven by the CXCL-CXCR2 axis, and polarization toward an antitumor state was programmed by treatment-induced IFN-γ and GM-CSF. TNF-α⁺ neutrophils enhanced CD8⁺ T-cell function via ICAM-1-LFA-1 interactions, and adoptive transfer confirmed their intrinsic antitumor activity in vivo. Spatial transcriptomics of patient tumor tissues further identified a TNF-α⁺ neutrophil-effector CD8⁺ T-cell niche after TRIDENT, providing a stimulatory signal to effector CD8⁺ T cells. In line with these mechanistic findings, clinical biomarker analyses linked neutrophil number with prolonged survival. TRIDENT activates an RT-driven neutrophil-CD8⁺ T-cell axis and promotes survival-associated neutrophil activation. These mechanistic insights, coupled with durable survival in our phase I trial, position TRIDENT as a promising strategy for metastatic NSCLC currently undergoing randomized phase II evaluation. Our study also highlights TNF-α⁺ neutrophils as a promising therapeutic strategy to enhance antitumor efficacy.

A 40-year-old man with acquired immunodeficiency syndrome (AIDS) presented with severe thrombocytopenia and disseminated Kaposi's sarcoma (KS). Initially diagnosed with immune thrombocytopenic purpura (ITP), he was treated with corticosteroids and antiretroviral therapy; however, his condition worsened. He met the criteria for Kaposi's sarcoma-associated inflammatory cytokine syndrome (KICS) and received liposomal doxorubicin, showing temporary improvement. KS progression was observed after immune recovery, suggesting KS-associated immune reconstitution inflammatory syndrome. Rituximab was administered, but the patient deteriorated and died. This case highlights the difficulty in distinguishing KICS from ITP, and the importance of an early diagnosis and multidisciplinary care in advanced AIDS.

Pembrolizumab is an immune checkpoint inhibitor that has been widely used in cancer treatment, and its approved indications have expanded rapidly in recent years. However, the effects of this increase on immune-related adverse events (irAEs) remain unclear. Using data from the Japanese Adverse Drug Event Report (JADER) database and the National Database of Health Insurance Claims and Specific Health Checkups (NDB Open Data), we analyzed trends in the number and characteristics of spontaneously reported adverse events associated with pembrolizumab from fiscal years 2016 to 2024. The number of adverse event reports in JADER generally increased in parallel with prescription volume. Following the expansion of indications for gynecological cancers (such as breast, uterus, and cervix cancers) around 2021, a marked increase in reports was observed from 2022. During this period, the demographic profile of reported patients shifted from predominantly older males to middle-aged females. Regarding cancer types, the proportion of reports on breast and uterus cancers increased significantly, whereas those on lung cancer declined. In addition to pulmonary disorders, endocrine disorders became increasingly reported and represented the most frequent category in fiscal year 2022. The distribution of irAEs by cancer type suggested potential associations; pulmonary toxicity was more frequent in lung cancer, whereas endocrine toxicity was predominant in breast, uterus, and cervix cancers. Our findings indicate that the expansion of pembrolizumab indications has substantially altered the profile of reported immune-related adverse events in Japan, highlighting the need for ongoing pharmacovigilance tailored to cancer type and patient demographics.

The numerous studies of the effects of intravenous anesthetics on cancer have suggested potential effects on cell migration and postoperative outcomes. This study compared the direct effects of midazolam and dexmedetomidine on A549 human lung adenocarcinoma cells.

A549 cells were exposed for 2 hr to midazolam (5, 10, 15, 20 μM), dexmedetomidine (1, 10, 100 nM), or medium alone as a naïve control. Cell viability changes were assessed with a wound healing assay, adenosine triphosphate (ATP) analysis, and cell counting kit-8 (CCK) assay. Tumor metastasis-related gene expression was assessed by a polymerase chain reaction (PCR) array and qRT-PCR. Hypoxia-inducible factor (HIF-1α), angiotensin-converting enzyme 2 (ACE2), matrix metalloproteinase (MMP9), and β-catenin expressions were assessed by immunofluorescence staining.

Midazolam treatments promoted cell migration and metabolism but suppressed cell proliferation, whereas D treatments promoted cell migration only and had no effect on metabolism or cell proliferation. The PCR array of cancer-related genes revealed that five genes were upregulated by midazolam treatment relative to naïve controls: Frizzled-1 (FZD1), AKT serine/threonine kinase 2 (AKT2), E2F transcription factor 1 (E2F1), Fos proto-oncogene, AP-1 transcription factor subunit (FOS), and tumor protein p53 (TP53). Two genes were upregulated in the dexmedetomidine group: the CRK proto-oncogene, adaptor protein (CRK) and FZD1.

These findings clarify how dexmedetomidine and midazolam treatments affect lung cancer prognoses. Our data suggest that midazolam rather than dexmedetomidine should be recommended for lung cancer surgery.

Comprehensive genomic profiling (CGP) tests have been covered by insurance in Japan since 2019, and their use in cancer genomic medicine (CGM) has expanded since then. Although extensive data are available from core hospitals, real-world data from community-based cooperative hospitals are limited.

Using data from 514 consecutive patients with advanced cancer who underwent CGP testing at our institution between June 2019 and March 2025, we investigated the proportion of cases receiving therapeutic recommendations, the rate of drug administration based on CGP test results, and the prevalence and management of presumed germline pathogenic variants (PGPVs).

The most common cancer sites were the pancreas (18.7%), breast (16.9%), bowel (14.6%), lung (12.8%), and prostate (12.5%). An expert panel made up of molecular oncologists recommended 360 targeted therapies for 311 patients (60.5% of the total cohort). Ultimately, 80 patients (15.6%) received matched therapy, among whom 56 received medication under health insurance coverage, 22 through clinical trials, and 2 via the patient-requested medical treatment system. PGPVs were identified in 68 patients (13.2%). After discussion by the expert panel, confirmatory germline testing was offered to patients with PGPVs, and subsequent germline testing confirmed pathogenic variants in 18 patients (3.5% of the total cohort).

The proportion of patients who received targeted therapy at our cooperative hospital was comparable to proportions reported from core hospitals. However, disease progression was a significant barrier to accessing targeted therapies and genetic counseling. To maximize the benefits of CGM, the timing of CGP testing must be optimized and collaboration across departments and institutions must be strengthened.

The internal oblique muscle free flap, based on the deep circumflex iliac artery, has emerged as a valuable option for oral reconstruction, due to its flexibility and the option to use it as a composite flap with iliac crest bone, for simultaneous bone and soft tissue reconstruction. However, clinical studies on the epithelialization process and factors influencing healing are limited. This retrospective study was performed to analyse the healing process in 29 patients who underwent reconstruction using internal oblique muscle free flaps following oral cancer resection at Chosun University Dental Hospital, between 2013 and 2022. Clinical photographs were evaluated to determine the times to epithelialization and surface maturation. The mean time to epithelialization was 5.6 ± 1.6 weeks, while surface maturation required 19.4 ± 10.9 weeks. Tongue defects showed the longest surface maturation period (30.3 weeks) and floor of the mouth defects the shortest (11.3 weeks), although there was no significant difference in this period between the various lesion sites. Pearson correlation revealed a strong positive relationship between time to epithelialization and time to surface maturation (r = 0.530, P = 0.003). Secondary trimming procedures were necessary in eight (27.6%) patients and significantly prolonged both epithelialization (P = 0.016) and surface maturation (P = 0.003). Age, lesion size, and other clinical variables did not significantly affect healing. The internal oblique muscle free flap demonstrated excellent outcomes with a 97.2% success rate and predictable healing patterns. This study established important healing benchmarks for patient counselling in oral reconstruction.

In the era of precision medicine, the growing number of predictive biomarkers have modified the clinical paradigm for advanced tumor patients. Standard tissue specimens are often limited for comprehensive genomic profiling for testing biomarkers. Liquid biopsy became a milestone in clinical stratification of advanced tumor patients integrating tissue based molecular analysis. International societies routinely approved peripheral blood integrating genomic profile of actionable biomarkers but unexplored scenarios expanding potential applications are under investigations. Within the term liquid biopsy, we include each biological fluid where circulating free DNA and beyond (circulating tumor cells, extracellular vesicles, tumor-educated platelets, and microRNAs) may be isolated.

Recent advances in molecular profiling, including next-generation sequencing and bioinformatic approaches, have enabled detailed characterization of tumor biology and facilitated patient stratification based on prognostic and predictive factors associated with clinical outcomes and therapeutic response. This article summarizes key biomarkers with established clinical relevance in kidney, bladder, and prostate cancers. In bladder and prostate cancer, novel insights into tumor biology have reshaped therapeutic strategies and supported the approval of targeted therapies, thereby enhancing patient care. Selecting appropriate molecular tests-such as FGFR screening in urothelial carcinoma and BRCA1/2 testing in prostate cancer-has become critical for guiding treatment decisions.

Colorectal carcinoma (CRC) is the most prevalent malignancy of the gastrointestinal tract and remains a leading cause of cancer-related illness and death worldwide. Recently, new treatment strategies have emerged with the identification of important biomarkers in CRC. As the emphasis on precision medicine in oncology intensifies, testing tumor specimens for key genomic alterations is becoming standard-of-care. This article seeks review the key molecular changes in CRC with important therapeutic implications.