Kim IH, et al. J Gastric Cancer. 2025 Jan;25:e11. https://doi.org/10.5230/jgc.2025.25.e11

As cancer immunotherapy using immune checkpoint inhibitors (ICIs) is rapidly evolving in clinical practice, it is necessary to identify biomarkers that will allow the selection of cancer patients who will benefit most or least from ICIs and to longitudinally monitor patients’ immune responses during treatment. Various peripheral blood-based immune biomarkers are being identified with recent advances in high-throughput multiplexed analytical technologies. The identification of these biomarkers, which can be easily detected in blood samples using non-invasive and repeatable methods, will contribute to overcoming the limitations of previously used tissue-based biomarkers. Here, we discuss the potential of circulating immune cells, soluble immune and inflammatory molecules, circulating tumor cells and DNA, exosomes, and the blood-based tumor mutational burden, as biomarkers for the prediction of immune responses and clinical benefit from ICI treatment in patients with advanced cancer.

Liver transplantation (LT) is a curative modality for hepatocellular carcinoma (HCC), especially in patients with cirrhosis. However, there are still risks of recurrence. C-reactive protein (CRP), an acute-phase inflammatory reactant that is synthesized by hepatocytes, has been related to the prognosis of various malignancies, including HCC. In this study, we investigated the role of a high CRP level in predicting the posttransplant outcomes of HCC patients. We analyzed 85 patients undergoing LT between August 2000 and July 2010 whose pretransplant serum CRP levels were available. Only 2 patients underwent deceased donor LT, and the remaining patients underwent living donor LT. With 1 mg/dL used as a cutoff value, 27 patients showed high CRP levels (≥1 mg/dL) at the time of LT, and 58 showed low CRP levels (<1 mg/dL). The total bilirubin level, Child-Pugh grade, Model for End-Stage Liver Disease score, maximal tumor size, and frequency of intrahepatic metastasis were significantly higher in the high-CRP group. According to multivariate analyses, HCC beyond the Milan criteria, a high CRP level, and microvascular invasion were related to tumor recurrence, and a high CRP level and microvascular invasion were related to poor overall survival. When a subgroup analysis was performed according to the Milan criteria, a high CRP level was an independent factor for predicting poor outcomes in patients with HCC beyond the Milan criteria (P = 0.02 for recurrence and P < 0.001 for survival) but not in patients with HCC within the criteria. Serum CRP could be considered a useful and cost-effective biomarker for predicting outcomes after LT for HCC, particularly in patients beyond the Milan criteria. Liver Transpl, 2012. © 2012 AASLD.

Accurate prediction of non-small cell lung cancer (NSCLC) prognosis after surgery remains challenging. The Cox proportional hazard (PH) model is widely used, however, there are some limitations associated with it. In this study, we developed novel neural network models called binned time survival analysis (DeepBTS) models using 30 clinico-pathological features of surgically resected NSCLC patients (training cohort, n = 1,022; external validation cohort, n = 298). We employed the root-mean-square error (in the supervised learning model, s- DeepBTS) or negative log-likelihood (in the semi-unsupervised learning model, su-DeepBTS) as the loss function. The su-DeepBTS algorithm achieved better performance (C-index = 0.7306; AUC = 0.7677) than the other models (Cox PH: C-index = 0.7048 and AUC = 0.7390; s-DeepBTS: C-index = 0.7126 and AUC = 0.7420). The top 14 features were selected using su-DeepBTS model as a selector and could distinguish the low- and high-risk groups in the training cohort (p = 1.86 × 10⁻¹¹) and validation cohort (p = 1.04 × 10⁻¹⁰). When trained with the optimal feature set for each model, the su-DeepBTS model could predict the prognoses of NSCLC better than the traditional model, especially in stage I patients. Follow-up studies using combined radiological, pathological imaging, and genomic data to enhance the performance of our model are ongoing.

Purpose: Although programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors are promising agents for recurrent or metastatic nasopharyngeal carcinoma (NPC), PD-1/PD-L1 inhibitor monotherapy has shown modest efficacy. This study evaluated the efficacy and safety of nivolumab plus gemcitabine in patients with NPC who failed prior platinum-based chemotherapy. Patients and Methods: This is a phase II, multicenter, open-label, single-arm study. Patients with recurrent or metastatic NPC received nivolumab 3 mg/kg and gemcitabine 1,250 mg/m2 every 2 weeks until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), overall survival (OS), and safety. To identify potential biomarkers, whole-exome sequencing, whole-transcriptome sequencing, and immune phenotype analysis based on Lunit SCOPE IO, an artificial intelligence–powered spatial tumor-infiltrating lymphocyte analyzer, were performed. Results: Thirty-six patients were enrolled between June 2018 and June 2019. The ORR was 36.1% and disease control rate was 97.2%. With median follow-up of 22.0 months, median PFS was 13.8 months [95% confidence interval (CI), 8.6–16.8 months]. Median OS was not reached, and OS rate at 6 months was 97.0% (95% CI, 80.4%–99.6%). The grade ≥3 treatment-related adverse events were hypertension (2.8%) and anemia (2.8%). In multivariate analysis of mutation of chromatin modifier gene, tumor mutational burden (≥ 2.1 mut/Mb), and somatic copy-number alteration (SCNA) level, the group with high SCNA (> 3 points; HR, 7.0; 95% CI, 1.3–37.9; P = 0.02) had independently associated with poor PFS. Immune phenotype analysis showed that tumors with high proportion of immune-excluded immune phenotype was significantly correlated with poor PFS (HR, 4.4; 95% CI, 1.2–16.2; P = 0.018). Conclusions: Nivolumab plus gemcitabine showed promising efficacy with favorable toxicity profiles in patients with advanced NPC in whom platinum-based combination chemotherapy failed.