Preoperative MRI is an essential diagnostic and therapeutic reference for gliomas. This study aims to evaluate the prognostic aspect of a radiomics biomarker for glioma and further investigate its relationship with tumor microenvironment and macrophage infiltration. We covered preoperative MRI of 664 glioma patients from three independent datasets: Jiangsu Province Hospital (JSPH, n = 338), The Cancer Genome Atlas dataset (TCGA, n = 252), and Repository of Molecular Brain Neoplasia Data (REMBRANDT, n = 74). Incorporating a multistep post-processing workflow, 20 radiomics features (Rads) were selected and a radiomics survival biomarker (RadSurv) was developed, proving highly efficient in risk stratification of gliomas (cut-off = 1.06), as well as lower-grade gliomas (cut-off = 0.64) and glioblastomas (cut-off = 1.80) through three fixed cut-off values. Through immune infiltration analysis, we found a positive correlation between RadSurv and macrophage infiltration (RMΦ = 0.297, p < 0.001; RM2Φ = 0.241, p < 0.001), further confirmed by immunohistochemical-staining (glioblastomas, n = 32) and single-cell sequencing (multifocal glioblastomas, n = 2). In conclusion, RadSurv acts as a strong prognostic biomarker for gliomas, exhibiting a non-negligible positive correlation with macrophage infiltration, especially with M2 macrophage, which strongly suggests the promise of radiomics-based models as a preoperative alternative to conventional genomics for predicting tumor macrophage infiltration and provides clinical guidance for immunotherapy. 

Noninvasive radiomics model reveals macrophage infiltration in glioma.

Accumulating evidence suggests the minority of patients with advanced pancreatic ductal adenocarcinoma (PDAC) that have microsatellite instability high (MSI-H) can benefit from immune checkpoint inhibitors (ICIs). However, the effects of ICIs on the tumor microenvironment (TME) of PDAC remain elusive. We conducted single-cell RNA-seq (scRNA-seq) analysis on a residual lesion from a MSI-H PDAC patient who received a radical operation after eight cycles of neoadjuvant treatment (nab-paclitaxel/gemcitabine plus pembrolizumab). Multiple tumor subclusters were identified in residual lesion after neoadjuvant treatment, one of which was mainly composed of cells in the S and G2M phases. This subcluster also had enriched expression of MKI67 and PCNA and cell cycle-related signatures and was thus defined as a proliferating tumor subcluster. This subcluster had higher S_score, Fatty acid_score, UPR_score, and Glycolysis_score than others. We also identified characteristics of the TME after neoadjuvant treatment by comparing the excised primary tumors form nontreated PDAC and the residual lesion. The residual lesion was characterized with activated pancreatic stellate cells (PSCs) and exhausted T cells (Tex). We compared the receptor-ligand interactions between the two groups, and found that no checkpoint receptor-ligand pairs between T cells and tumor cells were identified in the residual lesion, while there were many checkpoint receptor-ligand pairs in the nontreated primary PDAC. In conclusion, our findings revealed the characteristics of residual lesion of advanced PDAC with MSI-H upon combination treatment of chemotherapy and immunotherapy, which might provide some valuable clues for solving the puzzle of ICI in PDAC. 

Single-cell RNA-seq reveals characteristics in tumor microenvironment of PDAC with MSI-H following neoadjuvant chemotherapy with anti-PD-1 therapy.

Glioblastoma (GBM) progression is influenced by intratumoral heterogeneity. Emerging evidence has emphasized the pivotal role of extrachromosomal circular DNA (eccDNA) in accelerating tumor heterogeneity, particularly in GBM. However, the eccDNA landscape of GBM has not yet been elucidated. In this study, we first identified the eccDNA profiles in GBM and adjacent tissues using circle- and RNA-sequencing data from the same samples. A three-stage model was established based on eccDNA-carried genes that exhibited consistent upregulation and downregulation trends at the mRNA level. Combinations of machine learning algorithms and stacked ensemble models were used to improve the performance and robustness of the three-stage model. In stage 1, a total of 113 combinations of machine learning algorithms were constructed and validated in multiple external cohorts to accurately distinguish between low-grade glioma (LGG) and GBM in patients with glioma. The model with the highest area under the curve (AUC) across all cohorts was selected for interpretability analysis. In stage 2, a total of 101 combinations of machine learning algorithms were established and validated for prognostic prediction in patients with glioma. This prognostic model performed well in multiple glioma cohorts. Recurrent GBM is invariably associated with aggressive and refractory disease. Therefore, accurate prediction of recurrence risk is crucial for developing individualized treatment strategies, monitoring patient status, and improving clinical management. In stage 3, a large-scale GBM cohort (including primary and recurrent GBM samples) was used to fit the GBM recurrence prediction model. Multiple machine learning and stacked ensemble models were fitted to select the model with the best performance. Finally, a web tool was developed to facilitate the clinical application of the three-stage model. 

A three-stage eccDNA based molecular profiling significantly improves the identification, prognosis assessment and recurrence prediction accuracy in patients with glioma.

Activated fibroblasts, namely cancer-associated fibroblasts (CAFs), are highly heterogeneous in phenotypes, functions, and origins. CAFs originated from varieties of cell types, including local resident fibroblasts, epithelial cells, mesenchymal stromal cells, or others. These cells participate in tumor angiogenesis, mechanics, drug access, and immune suppression, with the latter being particularly important. It was difficult to distinguish CAFs by subsets due to their complex origins until the use of scRNA-seq. Reprogramming CAFs with TGFβ-RI inhibitor, a CXCR4 blocker, or other methods increases T cells activation and infiltration, together with a decrease in CAFs recruitment, thus improving the prognosis. As depletion of CAFs can't bring clinical benefit, the combination of reprogramming CAFs and immune checkpoint inhibitors (ICIs) come into consideration. It has shown better outcomes compared with monotherapy respectively in basic/preclinical researches, and needs more data on clinical trials. Combination therapy may be a promising and expecting method for treatment of cancer. 

Reprogramming of cancer-associated fibroblasts combined with immune checkpoint inhibitors: A potential therapeutic strategy for cancers.

Objective To investigate the need for and prognostic impact of gefitinib on the treatment of patients with early-stage epidermal growth factor receptor (EGFR) mutated non-small-cell lung cancer (NSCLC). Methods Clinical data of patients with stage IB-IIA non-squamous non-small-cell lung cancer admitted to our thoracic surgery department from January 2020 to January 2022 were collected, and a total of 94 cases were included, divided into 44 cases in the control group (EGFR mutation-negative) and 50 cases in the experimental group (EGFR mutation-positive (including those on medication (19 cases) and those not on medication (31 cases)) according to the outcome of EGFR mutation. To evaluate the necessity and prognostic effect of gefitinib in the treatment of NSCLC patients with early EGFR mutations. Results The lung cancer recurrence rate in the experimental group (66.00%) was higher than that in the control group (40.91%), and the difference was statistically significant (χ2 = 5.937, P=0.015); in the subgroup analysis of the experimental group samples, the pharmacological intervention of gefitinib had a significant effect on lung cancer recurrence (χ2 = 7.797, P=0.005), and the proportion of lung cancer recurrence in patients not taking the drug (80.65%) was significantly higher than in the drug-taking group (42.11%); the median survival time was 53.6 months using EGFR mutation type as the study factor, with a statistically significant difference in change in 5-year survival rate for EGFR mutation type (χ2 = 6.095, P=0.047) and the lowest 5-year survival rate for subjects with EGFR mutation type Exon 20 T790M. Conclusion Patients with early gene drive positive lung adenocarcinoma are significantly more likely to recur and metastasise and have shorter survival times in the absence of pharmacological intervention.

/pdf/the-effect-of-gefitinib-on-treatment-necessity-and-prognosis-2ik9xlz0.pdf

The Effect of Gefitinib on Treatment Necessity and Prognosis of NSCLC Patients with Early EGFR Mutations

Immunotherapy of cholangiocarcinoma: Therapeutic strategies and predictive biomarkers.

Simple Summary The underlying mechanism of post-operative relapse of non-small cell lung cancer (NSCLC) remained poorly understood. This study highlights that both tumors and adjacent tissues from stage I NSCLC with relapse show a dysregulated immune and metabolic environment. Immune response shifts from an active state in primary tumors to a suppressive state in recurrent tumors. A model based on the enriched biological features in the primary tumors with relapse could effectively predict recurrence for stage I NSCLC. These results provide insights into the underpinning of the post-operative relapse and suggest that identifying NSCLC patients with a high risk of relapse could help the clinical decision of applying appropriate therapeutic interventions. Abstract The underlying mechanism of post-operative relapse of non-small cell lung cancer (NSCLC) remains poorly understood. We enrolled 57 stage I NSCLC patients with or without relapse and performed whole-exome sequencing (WES) and RNA sequencing (RNA-seq) on available primary and recurrent tumors, as well as on matched tumor-adjacent tissues (TATs). The WES analysis revealed that primary tumors from patients with relapse were enriched with USH2A mutation and 2q31.1 amplification. RNA-seq data showed that the relapse risk was associated with aberrant immune response and metabolism in the microenvironment of primary lesions. TATs from the patients with relapse showed an immunosuppression state. Moreover, recurrent lesions exhibited downregulated immune response compared with their paired primary tumors. Genomic and transcriptomic features were further subjected to build a prediction model classifying patients into groups with different relapse risks. We show that the recurrence risk of stage I NSCLC could be ascribed to the altered immune and metabolic microenvironment. TATs might be affected by cancer cells and facilitate the invasion of tumors. The immune microenvironment in the recurrent lesions is suppressed. Patients with a high risk of relapse need active post-operative intervention.

/pdf/dysregulated-immune-and-metabolic-microenvironment-is-1mnz645x.pdf

Dysregulated Immune and Metabolic Microenvironment Is Associated with the Post-Operative Relapse in Stage I Non-Small Cell Lung Cancer

/pdf/effects-of-acupuncture-on-gastrointestinal-function-in-19h4ypcc.pdf

Effects of acupuncture on gastrointestinal function in enhanced recovery after surgery patients: a systematic review and meta-analysis of randomized controlled trials

Abstract Background With the advent of intensive combination regimens, an increasing number of patients with unresectable pancreatic cancer (UPC) have regained the opportunity for surgery. We investigated the clinical benefits and prognostic factors of conversion surgery (CS) in UPC patients. Methods We retrospectively enrolled patients with UPC who had received CS following first-line systemic treatment in our center between 2014 to 2022. Treatment response, safety of the surgical procedure and clinicopathological data were collected. We analyzed the prognostic factors for postoperative survival among UPC patients who had CS. Results Sixty-seven patients with UPC were enrolled (53 with locally advanced pancreatic cancer (LAPC) and 14 with metastatic pancreatic cancer (MPC)). The duration of preoperative systemic treatment was 4.17 months for LAPC patients and 6.52 months for MPC patients. All patients experienced a partial response (PR) or had stable disease (SD) preoperatively according to imaging. Tumor resection was unsuccessful in four patients and, finally, R0 resection was obtained in 81% of cases. Downstaging was determined pathologically in 87% of cases; four patients achieved a complete pathological response. Median postoperative-progression-free survival (PO-PFS) was 9.77 months and postoperative overall survival (PO-OS) was 31.2 months. Multivariate logistic regression analyses revealed that the resection margin and postoperative changes in levels of tumor markers were significant prognostic factors for PO-PFS. No factors were associated significantly with PO-OS according to multivariate analyses. Conclusions CS is a promising strategy for improving the prognosis of UPC patients. The resection margin and postoperative change in levels of tumor markers are the most important prognostic factors for prolonged PFS. Multidisciplinary treatment in high-volume centers is strongly recommended. Prospective studies must be undertaken to resolve the various problems regarding optimal regimens, the duration of treatment, and detailed criteria for CS. 

https://bmccancer.biomedcentral.com/counter/pdf/10.1186/s12885-023-10529-7

Normalization of tumor markers and a clear resection margin affect progression-free survival of patients with unresectable pancreatic cancer who have undergone conversion surgery

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Papers

Immunotherapy of cholangiocarcinoma: Therapeutic strategies and predictive biomarkers.

Dysregulated Immune and Metabolic Microenvironment Is Associated with the Post-Operative Relapse in Stage I Non-Small Cell Lung Cancer

Effects of acupuncture on gastrointestinal function in enhanced recovery after surgery patients: a systematic review and meta-analysis of randomized controlled trials

Normalization of tumor markers and a clear resection margin affect progression-free survival of patients with unresectable pancreatic cancer who have undergone conversion surgery