National Cancer Center

Utakata et al. reported that admission serum amino acid imbalance—assessed by branched-chain amino acids (BCAAs), tyrosine and the BCAA-to-tyrosine ratio (BTR)—is independently associated with mortality among hospitalised patients with cirrhosis [1]. Using a large multicentre cohort with long-term follow-up, the authors demonstrate that low BTR, decreased BCAA levels, and increased tyrosine levels retain prognostic significance after adjustment for established clinical factors. These findings are clinically relevant and support renewed attention to metabolic profiling in cirrhosis risk stratification. Several clarifications could further strengthen the clinical applicability of these results. First, the reported hazard ratios for continuous BCAA and tyrosine concentrations are expressed per 1 μmol/L, yielding effect estimates that appear numerically close to unity. While statistically significant, such scaling limits bedside interpretability. Reporting hazard ratios per standard deviation, interquartile-range change, or clinically meaningful increments (e.g., 50–100 μmol/L), with greater decimal precision, would better convey the magnitude of risk and facilitate comparison with existing prognostic markers. In addition, visualising non-linear associations using restricted cubic splines may help identify thresholds relevant to clinical decision-making, particularly given the use of predefined cut-offs in survival analyses. Second, amino acid imbalance closely tracks liver functional reserve and nutritional status. In the present cohort, patients with low BTR had markedly worse Child–Pugh class, MELD score, albumin, bilirubin, platelet count, and ammonia levels. Although multivariable adjustment was performed, additional sensitivity analyses may enhance confidence that amino acid measures provide incremental prognostic information beyond conventional scores. Models incorporating MELD-Na or individual components (including creatinine) alongside BTR or its components, as well as reporting proportional hazards assumption checks, would clarify the robustness of the observed associations and support their use in routine risk stratification. Third, from a clinical perspective, it would be valuable to delineate how amino acid profiling might complement existing prognostic frameworks. Quantifying improvements in discrimination or calibration—such as changes in C-index or risk reclassification when BTR or tyrosine is added to established models—would directly address whether these markers meaningfully refine risk stratification rather than simply reflect disease severity. Such analyses could help identify patient subgroups in whom early nutritional assessment or targeted interventions may be most beneficial. Overall, this well-conducted study provides compelling evidence that amino acid imbalance is associated with mortality in cirrhosis. Addressing the points above would further strengthen the clinical message and clarify how BTR, BCAA, and tyrosine measurements can be integrated into practical prognostic assessment to guide follow-up intensity and supportive care strategies. Sincerely, Seoung Hoon Kim Seoung Hoon Kim: conceptualization, investigation, writing – original draft, writing – review and editing, supervision, methodology. The author has nothing to report. The author declares no conflicts of interest. This article is linked to Utakata et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70525 and https://doi.org/10.1111/apt.70592. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

Photodynamic therapy (PDT) is a promising cancer treatment, yet its efficacy is often compromised by tumor hypoxia and limited immune activation. Here, we developed a multifunctional photosynthetic nanoplatform (PnanoCB) derived from Microcystis wesenbergii to alleviate hypoxia, enhance reactive oxygen species (ROS)-mediated tumor cell killing, and activate antitumor immunity. The cyanobacteria were restructured into protoplast-derived vesicles, retaining photosynthetic capacity and chlorophyll, and functionalized with a Matrix metalloproteinase-2 (MMP-2)-cleavable anti-PD-L1 peptide via a pH-sensitive pH low insertion peptide (pHLIP) linker for tumor-targeted immune checkpoint blockade. Upon red light irradiation, PnanoCB efficiently generated oxygen in situ, overcoming hypoxia and significantly amplifying PDT-induced ROS production. Combining PnanoCB with a fasting-mimicking diet (FMD) further improved tumor accumulation and therapeutic efficacy. The combination of PnanoCB, light irradiation, and FMD achieved the most potent tumor inhibition in a 4T1 breast cancer model and effectively prevented tumor recurrence in a rechallenge model, without detectable toxicity to major organs. Overall, PnanoCB significantly alleviates hypoxia, promotes immunogenic cell death, and triggers robust dendritic cell (DC) maturation through stimulator of interferon genes (STING) pathway activation. This study demonstrates a strategy integrating photosynthetic oxygen generation, photodynamic immunotherapy, and metabolic intervention to remodel the tumor microenvironment and elicit robust systemic antitumor immunity.

Minimal residual disease (MRD) detection using liquid biopsy is an emerging tool for risk stratification and monitoring for recurrence in resected early stage NSCLC. There is increasing need for clear guidance on its optimal clinical implementation. The Asian Thoracic Oncology Research Group (ATORG) convened a multidisciplinary panel of 27 experts to develop a consensus statement on the clinical application of circulating tumor DNA-based MRD testing in early stage resected NSCLC, using a structured Delphi methodology. Statements were organized into the following broad thematic domains: assay validity and standardization; harmonization in research and trials; clinical application; challenges in implementation; consensus recommendations; infrastructure for regional MRD adoption; and roadmap for pragmatic trials. A total of 23 position statements were developed, of which all except one achieved strong consensus. The consensus highlighted the need to define minimum analytical performance thresholds for MRD assays, improve standardization of reporting metrics, and clear guidelines for pre-analytical handling. Harmonization of blood sampling time points and terminology across clinical trials is also essential to confirm the prognostic value of MRD assays. Although current MRD assays demonstrate high specificity and positive predictive value, variable sensitivity precludes routine use for adjuvant therapy de-escalation outside clinical trials. Broader access, sustainable funding, ongoing consensus building, and collaborative real-world data generation are also critical to support clinical implementation and adoption. Future clinical trials must account for the distinct biology and changing standards of care associated with different driver genes. These consensus recommendations provide a pragmatic framework to guide the responsible integration of MRD testing into clinical research and practice.