Tumor Node Research Articles

Multi-modality radiomics model predicts axillary lymph node metastasis of breast cancer using MRI and mammography.

We aimed to develop a multi-modality model to predict axillary lymph node (ALN) metastasis by combining clinical predictors with radiomic features from magnetic resonance imaging (MRI) and mammography (MMG) in breast cancer. This model might potentially eliminate unnecessary axillary surgery in cases without ALN metastasis, thereby minimizing surgery-related complications. We retrospectively enrolled 485 breast cancer patients from two hospitals and extracted radiomics features from tumor and lymph node regions on MRI and MMG images. After feature selection, three random forest models were built using the retained features, respectively. Significant clinical factors were integrated with these radiomics models to construct a multi-modality model. The multi-modality model was compared to radiologists' diagnoses on axillary ultrasound and MRI. It was also used to assist radiologists in making a secondary diagnosis on MRI. The multi-modality model showed superior performance with AUCs of 0.964 in the training cohort, 0.916 in the internal validation cohort, and 0.892 in the external validation cohort. It surpassed single-modality models and radiologists' ALN diagnosis on MRI and axillary ultrasound in all validation cohorts. Additionally, the multi-modality model improved radiologists' MRI-based ALN diagnostic ability, increasing the average accuracy from 70.70 to 78.16% for radiologist A and from 75.42 to 81.38% for radiologist B. The multi-modality model can predict ALN metastasis of breast cancer accurately. Moreover, the artificial intelligence (AI) model also assisted the radiologists to improve their diagnostic ability on MRI. The multi-modality model based on both MRI and mammography images allows preoperative prediction of axillary lymph node metastasis in breast cancer patients. With the assistance of the model, the diagnostic efficacy of radiologists can be further improved. • We developed a novel multi-modality model that combines MRI and mammography radiomics with clinical factors to accurately predict axillary lymph node (ALN) metastasis, which has not been previously reported. • Our multi-modality model outperformed both the radiologists' ALN diagnosis based on MRI and axillary ultrasound, as well as single-modality radiomics models based on MRI or mammography. • The multi-modality model can serve as a potential decision support tool to improve the radiologists' ALN diagnosis on MRI.

Comparative Analysis of US Guidelines for the Management of Cutaneous Squamous Cell and Basal Cell Carcinoma.

This study presents a comparative analysis of recently published guidelines to manage cutaneous squamous cell carcinoma (cSCC) and cutaneous basal cell carcinoma (cBCC) within the United States (US). A PubMed database search was performed for the time period between June 1, 2016, and December 1, 2022. A comprehensive comparison was performed in the following clinical interest areas: staging and risk stratification, management of primary tumor and regional nodes with curative intent, and palliative treatment. Guidelines from 3 organizations were analyzed: the American Academy of Dermatology (AAD), the National Comprehensive Cancer Network (NCCN), and the American Society for Radiation Oncology (ASTRO). The guidelines used different methodologies to grade evidence, making comparison difficult. There was agreement that surgery is the preferred treatment for curative cBCC and cSCC. For patients ineligible for surgery, there was a consensus to recommend definitive radiation. AAD and NCCN recommended consideration of other topical modalities in selected low-risk cBCC. Postoperative radiation therapy (PORT) was uniformly recommended in patients with positive margins that could not be cleared with surgery and in patients with nerve invasion. The definition and extent of nerve invasion varied. All guidelines recommended surgery as the primary treatment in patients with lymph node metastases in a curative setting. The criteria used for PORT varied; NCCN and ASTRO used lymph node size, number of nodes, and extracapsular extension for recommending PORT. Both NCCN and ASTRO recommend consideration of systemic treatment along with PORT in patients with extracapsular extension. Conclusion: US guidelines provide contemporary and complementary information on the management of cBCC and cSCC. There are opportunities for research, particularly in the areas of staging, indications for adjuvant treatment in curative settings, extent of nerve invasion and prognosis, and the role of systemic treatments in curative and palliative settings.

Clinical diagnosis and treatment analysis of 21 cases of intrathyroid thymic carcinoma

Objective: To analyze the clinical efficacy of intrathyroid thymic carcinoma (ITTC). Methods: This study retrospectively analyzed the clinical data of 21 patients with ITTC diagnosed and treated at the First Affiliated Hospital of Zhengzhou University from January 2018 to July 2023, including 9 males and 12 females, with a median age of 52 years (40-60 years old). Results: There is a correlation between the maximum diameter of the tumor (≥40 mm) and lymph node metastasis (P=0.044). Seventeen patients received surgical treatment, and 4 patients only received chemotherapy. During the follow-up period, a total of 4 patients experienced death or progression, with a 2-year mortality or progression free survival rate of 74.8%. Conclusions: The prognosis of ITTC is good, and surgical treatment is the preferred treatment option, lymph node metastasis is significantly correlated with prognosis. The radiotherapy and chemotherapy of ITTC need to be determined based on the patient's condition.

Association between PET–CT accumulation in the hypothalamic/pituitary regions and neuron-specific enolase/primary tumor in limited-stage small cell lung cancer: a case-controlled retrospective study

BackgroundResearch on the relationship between neuron-specific enolase (NSE) levels and normal organs, particularly the central nervous system, in small cell lung cancer is limited. Therefore, this study aimed to investigate the relationship between positron emission tomography–computed tomography (PET–CT) accumulation at hypothalamic/pituitary regions, tumor activity, and NSE level in limited-stage small cell lung cancer. We retrospectively analyzed patients who were diagnosed with limited-stage small cell lung cancer at Tokyo Medical University Hospital between July 1, 2019, and May 31, 2023, and were treated with chemoradiotherapy or radiotherapy. Leukocytes, erythrocytes, hemoglobin, platelets, total protein, albumin, NSE, and carcinoembryonic antigen were measured in blood samples obtained before treatment initiation. The maximum standardized uptake value (SUVmax), volume, and total lesion glycolysis (TLG) of each hypothalamic /pituitary region, primary tumor, and lymph node metastases were extracted from PET–CT images. The total tumor volume (primary tumor volume plus lymph node metastases volume) and total TLG (primary tumor TLG plus lymph node metastases TLG) were calculated.ResultsThis study included 19 patients (mean age, 70.1 ± 8.8 years; 13 men and 6 women); the pathology in all patients was small cell lung cancer. Patients were classified into two groups according to the NSE reference value (16.3 ng/mL): six patients having NSE level below the reference value and 13 having NSE level above the reference value. The SUVmax in the hypothalamic/pituitary region was 2.95 in the NSE < 16.3 ng/mL group and 4.10 in the NSE > 16.3 ng/mL group, with a statistically significant difference (p = 0.03). The total tumor volume was 17.8 mL in the NSE < 16.3 ng/mL group and 98.9 mL in the NSE > 16.3 ng/mL group, with a statistically significant difference (p < 0.01). A correlation coefficient of r = 0.458 (p = 0.0486) was observed between SUVmax in the hypothalamus/pituitary and NSE level. A correlation coefficient of r = 0.647 (p < 0.01) was also observed between total tumor volume and NSE level. Finally, a correlation coefficient of r = 0.53 (p = 0.01) was observed between hypothalamic/pituitary TLG and primary tumor TLG.ConclusionsThe findings demonstrated a correlation between hypothalamic/pituitary activity and tumor activity, suggesting the prognostic significance of NSE.

Breaking-Down Tumoral Physical Barrier by Remotely Unwrapping Metal-Polyphenol-Packaged Hyaluronidase for Optimizing Photothermal/Photodynamic Therapy-Induced Immune Response.

The therapy of solid tumors is often hindered by the compact and rigid tumoral extracellular matrix (TECM). Precise reduction of TECM by hyaluronidase (HAase) in combination with nanotechnology is promising for solid tumor therapeutics, yet remains an enormous challenge. Inspired by the treatment of iron poisoning, here a remotely unwrapping strategy is proposed of metal-polyphenol-packaged HAase (named PPFH) by sequentially injecting PPFH and a clinically used iron-chelator deferoxamine (DFO). The in situ dynamic disassembly of PPFH can be triggered by the intravenously injected DFO, resulting in the release, reactivation, and deep penetration of encapsulated HAase inside tumors. Such a cost-effective HAase delivery strategy memorably improves the subsequent photothermal and photodynamic therapy (PTT/PDT)-induced intratumoral infiltration of cytotoxic T lymphocyte cells and the cross-talk between tumor and tumor-draining lymph nodes (TDLN), thereby decreasing the immunosuppression and optimizing tumoricidal immune response that can efficiently protect mice from tumor growth, metastasis, and recurrence in multiple mouse cancer models. Overall, this work presents a proof-of-concept of the dynamic disassembly of metal-polyphenol nanoparticles for extracellular drug delivery as well as the modulation of TECM and immunosuppressive tumor microenvironment.

Oncologic Outcome of Patients With Pathologic T0 Esophageal Squamous Cell Carcinoma After Neoadjuvant Chemoradiotherapy.

To investigate the oncologic outcomes of patients with esophageal squamous cell carcinoma (ESCC) who have achieved a pathologic complete response (pCR) of the primary tumor (ypT0) after neoadjuvant chemoradiotherapy (NCRT). Patients with thoracic ESCC who underwent scheduled NCRT followed by surgery at our hospital between January 2010 and December 2022 were retrospectively analyzed. Only patients with ypT0 disease were enrolled in this study. A total of 118 patients were ultimately enrolled in this study. Ninety-two patients achieved pCR in the primary tumor and lymph nodes (ypT0N0), while 26 patients had residual metastatic disease in 52 lymph nodes (ypT0N+). Forty-five of the 52 lymph nodes with residual tumors were abdominal lymph nodes. Positive lymph nodes were more often observed in patients with tumors located in the lower third of the esophagus. The 1-, 3-, and 5-year overall survival (OS) rates for the entire study group were 96.5%, 79.5%, and 77.1%, and the 1-, 3-, and 5-year disease-free survival (DFS) rates were 90.5%, 76.8%, and 69.0%, respectively. According to multivariate analyses, pN classification was an independent predictor of both OS and DFS (P < 0.05), while sex and cT classification were also found to be independent prognostic factors for DFS (P < 0.05). Residual nodal metastatic disease in patients with ypT0 ESCC after NCRT was more often found in the abdominal lymph nodes. pN classification was an independent predictor of both OS and DFS for ypT0 ESCC patients after NCRT.

Tumor and metastatic lymph nodes metabolic activity on 18F-FDG-PET/CT to predict progression-free survival in locally advanced cervical cancer.

The present study investigated the predictive diseases progression value of preoperative fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with local advanced cervical cancer (LACC). In total, 267 patients [median age 58 (range: 27-85) years old] with LACC underwent 18F-FDG PET/CT prior to any treatment. The maximum standardized uptake values (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary lesion and metastatic lymph nodes were measured on PET/CT and correlated with clinicopathological features and progression-free survival (PFS). The median follow-up was 36.52 (range: 3.09-61.29) months. During the observation period, 80 (30.0%) patients exhibited disease progression. Univariate analysis showed that FIGO stage, concurrent chemoradiotherapy (CRT), serum level of carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag), primary tumor MTV (pMTV) and TLG (pTLG), lymph nodes SUVmax (nSUVmax) and TLG (nTLG), and total metabolic activity (sMTV, sTLG) were associated with PFS. nSUVmax ≥ 5.29, CEA ≥ 7.11ng/ml and deficiency of concurrent CRT were independent risk factor for PFS (p = 0.006, p = 0.008, p = 0.014). The 3-year PFS for patients with high nSUVmax were 42.2% compared to 56.3% for low nSUVmax values. Pretreatment cervical and lymph nodes metabolic parameters were associated with PFS in patients with LACC.

Overexpression of KLHL22 correlates with poor prognosis in patients with triple-negative breast cancer.

Kelch-like family member 22 (KLHL22) is a protein-coding gene that is responsible for several Mendelian diseases and has been reported to promote tumorigenesis and aging. The purpose of this study was to investigate its expression in triple-negative breast cancer (TNBC) and its prognostic significance. Immunohistochemistry (IHC) was performed to examine the expression levels of KLHL22 in 146 patients with TNBC. The Chi-squared test was used to analyze the correlations between KLHL22 expression level and clinicopathological features, and the Kaplan-Meier survival analysis and Cox multivariate regression model were used to analyze the prognostic significance of KLHL22 in patients with TNBC. The results of immunohistochemical analysis showed that the high expression rate of KLHL22 protein in TNBC was 56.85% (83/146). Further analysis revealed a significantly positive correlation (P<0.05) between KLHL22 expression and primary tumor and regional lymph node status, clinical stage, and relapse. Kaplan-Meier survival analysis revealed that patients with low KLHL22 expression had a longer mean survival time than those with high KLHL22 expression (147.93 vs. 90.1 months; P<0.05). In the multivariate analysis, KLHL22 level, P53 expression, and clinical stage were found to be independent prognostic factors for overall survival (P<0.05), while clinical stage and KLHL22 level were independent prognostic factors for progression-free survival (P<0.05). The present study concludes that KLHL22 may serve as a biomarker for poor prognosis in patients with TNBC.

Long-term outcomes of intensity-modulated radiotherapy in limited-stage small-cell lung cancer classified according to AJCC 8th tumor node metastasis staging system.

The objective of this study was to assess treatment outcomes of intensity-modulated radiotherapy with concomitant chemotherapy and to identify prognostic factors on survival in patients with limited-stage small-cell lung cancer. A retrospective analysis was conducted on a cohort of seventy-two patients who received curative treatment between December 2011 and January 2023. Several clinical and biochemical parameters were examined as potential prognostic factors. The median age was 63 years, and 79% of them were males. Concomitant chemotherapy was administered in 83% of patients. Prophylactic cranial irradiation was applied in 61% of the cohort. Two and five-year overall survival (OS), disease-free survival (DFS), and local relapse-free survival (LRFS) rates were 50% and 25%, 38% and 24%, and 44% and 25%, respectively. Univariate analysis revealed that older age, comorbid lung disease, advanced tumor-node-metastasis (TNM) stage, radiotherapy (RT) alone, and the absence of prophylactic cranial irradiation (PCI) were adverse factors affecting OS. The advanced TNM stage emerged as a significant prognostic factor for LRFS and DFS, with a notable trend toward affecting OS. The TNM staging system is of significance in cases classified as limited-stage small-cell lung cancer due to its prognostic implications. Our results suggest that patients with more advanced TNM stage exhibit less favorable treatment outcomes, which may require individual tailoring of new systemic therapies.

Systemic immune index predicts tumor-infiltrating lymphocyte intensity and immunotherapy response in small cell lung cancer.

Despite recent progresses in immune checkpoint blockade (ICB) in small-cell lung cancer (SCLC), a lack of understanding regarding the systemic tumor immune environment (STIE) and local tumor immune microenvironment (TIME) makes it difficult to accurately predict clinical outcomes and identify potential beneficiaries from ICB therapy. We enrolled 191 patients with stage I-III SCLC and comprehensively evaluated the prognostic role of STIE by several quantitative measurements, and further integrate it with a local immune score system (LISS) established by eXtreme Gradient Boosting (XGBoost) machine learning algorithm. We also test the value of STIE in beneficiary selection in our independent advanced SCLC cohort receiving programmed cell death 1 ligand 1 (PD-L1) blockade therapy. Among several systemic immune markers, the STIE as assessed by prognostic nutritional index (PNI) was correlated with disease-free survival (DFS) and overall survival (OS), and remained as an independent prognostic factor for SCLC patients [hazard ratio (HR): 0.473, 95% confidence interval (CI): 0.241-0.929, P=0.030]. Higher PNI score was closely associated with inflamed SCLC molecular subtype and local tumor-infiltrating lymphocytes (TILs). We further constructed a LISS which combined top three important local immune biomarkers (CD8+ T-cell count, PD-L1 expression on CD8+ T-cell and CD4+ T-cell count) and integrated it with the PNI score. The final integrated immune risk system was an independent prognostic factor and achieved better predictive performance than Tumor Node Metastasis (TNM) stages and single immune biomarker. Furthermore, PNI-high extensive-stage SCLC patients achieved better clinical response and longer progression-free survival (PFS) (11.8 vs. 5.9 months, P=0.012) from PD-L1 blockade therapy. This study provides a method to investigate the prognostic value of overall immune status by combining the PNI with local immune biomarkers in SCLC. The promising clinical application of PNI in efficacy prediction and beneficiary selection for SCLC immunotherapy is also highlighted.

Prognostic implications of T stage in different pathological types of colorectal cancer: an observational study using SEER population-based data

ObjectivesColorectal cancer (CRC) encompasses a spectrum of pathological types, each exhibiting distinct biological behaviours that challenge the conventional T-staging system’s predictive efficiency. Thus, this study aims to explore the prognostic...

EFFECTIVENESS AND SAFETY OF CARBOPLATIN-CONTAINING ANTITUMOR THERAPY REGIMENS IN A MODEL OF COEXISTANCE OF LUNG CARCINOMA AND TUBERCULOSIS

Introduction. Treatment of the coexistent pathology of lung cancer and tuberculosis remains the prerogative of experimental research, since the optimal treatment strategy for the coexistence of these two diseases has not yet been developed. The purpose was to study the effectiveness and safety of carboplatin-containing antitumor therapy regimens in combination with anti-tuberculosis chemotherapy. Material and methods. The study was conducted on 64 C57BL/6 mice aged two months with a previously modeled coexistant pathology of lung carcinoma and tuberculosis. Depending on the therapy, 4 groups were formed: 1 – control without treatment (n=16), 2 – antitumor (carboplatin + paclitaxel) + antituberculosis therapy (n=16), 3 – antitumor (carboplatin + pemetrexed) + antituberculosis therapy (n=16), 4 – antitumor (carboplatin + gemcitabine) + anti-tuberculosis therapy (n=16). The anti-tuberculosis therapy regimen included the administration of isoniazid, rifampicin, pyrazinamide and ethambutol. The antitumor effect (tumor growth index, tumor growth inhibition), antituberculosis effect (CFU per lung weight), toxicity (clinical blood test parameters, biometric indicators of internal organs), and survival were assessed. Statistical processing was carried out using non-parmetric statistics methods. Results. The lowest average body weight was recorded in group 4 from 7 to 21 days. The greatest differences between groups in the volume of the tumor node were observed from 12 to 16 days of the experiment under the influence of antitumor drugs. At the same time, the greatest inhibition of tumor growth was observed in group 4. On day 9 in group 2 there were signs of the myelo-immunosuppressive effect of antitumor therapy in the form of a decrease in the concentration of leukocytes, lymphocytes and monocytes. In the study groups, there were no statistically significant differences in the survival rate of the experimental and control groups. In all experimental groups, significantly lower spleen MC values were recorded, and in group 4, significantly lower liver MC values were also recorded. The highest level of mycobacterial load was recorded in the control group. The lowest CFU per lung weight was found in the carboplatin and gemcitabine treatment group. Conclusion. Carboplatin-containing chemotherapy regimens for lung carcinoma in tuberculosis-infected mice have both antitumor and antituberculosis effects. The most pronounced antimycobacterial activity was recorded when using a combination of antituberculosis therapy with carboplatin and gemcitabine.

Comparison of different criteria for estimating major pathological response in resectable non-small cell lung cancer treated with neoadjuvant chemoimmunotherapy

BackgroundMajor pathological response (MPR) is proposed as a surrogate endpoint for survival in non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy. However, the criteria for estimating MPR differ between the recommendations of the International Association for the Study of Lung Cancer (IASLC) and the immune-related pathologic response criterion (irPRC). IASLC's criteria focus solely on evaluating the primary tumor, while irPRC's criteria encompass both the primary tumor and lymph node metastasis. Our objective is to compare the prognostic value of different criteria for estimating MPR. MethodsWe conducted a retrospective study on a cohort of 235 patients with NSCLC after neoadjuvant chemoimmunotherapy. The survival endpoint was event-free survival (EFS). The MPR status of each patient was evaluated using both IASLC's criteria and irPRC's criteria. The prognostic value was compared using the Area Under Curve (AUC). ResultsThe MPR rates were 63.4 % (149/235) and 57.4 % (135/235) according to IASLC's and irPRC's criteria, respectively. Inconsistent cases, characterized by MPR status according to IASLC's criteria but non-MPR status according to irPRC's criteria, constituted 6.0 % (14/235) of the overall cohort and 15.2 % (14/92) of patients with pretreatment N positive disease. Interestingly, all inconsistent patients showed no recurrence during the study period. Although both MPR statuses according to IASLC (p = 0.00039) and irPRC (p = 0.0094) were associated with improved EFS, IASLC's criteria (AUC = 0.65) were superior to irPRC's criteria (AUC = 0.62) with a higher AUC value. ConclusionIASLC's criteria for estimating MPR were superior to irPRC's criteria in predicting EFS for NSCLC after neoadjuvant chemoimmunotherapy.

Bioinformatics analysis identifies coagulation factor II receptor as a potential biomarker in stomach adenocarcinoma

Coagulation factor 2 thrombin receptor (F2R), a member of the G protein-coupled receptor family, plays an important role in regulating blood clotting through protein hydrolytic cleavage mediated receptor activation. However, the underlying biological mechanisms by which F2R affects the development of gastric adenocarcinoma are not fully understood. This study aimed to systematically analyze the role of F2R in gastric adenocarcinoma. Stomach adenocarcinoma (STAD)-related gene microarray data and corresponding clinicopathological information were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differential expression genes (DEGs) associated with F2R were analyzed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), and protein–protein interaction (PPI) networks. F2R mRNA expression data were utilized to estimate stromal cell and immune cell scores in gastric cancer tissue samples, including stromal score, immune score, and ESTIMATE score, derived from single-sample enrichment studies. Analysis of TCGA and GEO databases revealed significantly higher F2R expression in STAD tissues compared to normal tissues. Patients with high F2R expression had shorter survival times than those with low F2R expression. F2R expression was significantly correlated with tumor (T) stage, node (N) stage, histological grade and pathological stage. Enrichment analysis of F2R-related genes showed that GO terms were mainly related to circulation-mediated human immune response, immunoglobulin, cell recognition and phagocytosis. KEGG analysis indicated associations to extracellular matrix (ECM) receptor interactions, neuroactive ligand-receptor interactions, the phosphoinositide-3-kinase-protein kinase B/Akt (PI3K-AKT) signaling pathway, the Wnt signaling pathway and the transforming growth factor-beta (TGF-β) signaling pathway. GSEA revealed connections to DNA replication, the Janus kinase/signal transducers and activators of transcription (JAK-STAT) signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway and oxidative phosphorylation. Drug sensitivity analysis demonstrated positive correlations between F2R and several drugs, including BEZ235, CGP-60474, Dasatinib, HG-6-64-1, Aazopanib, Rapamycin, Sunitinib and TGX221, while negative correlation with CP724714, FH535, GSK1904529A, JNK-9L, LY317615, pyrimidine, rTRAIL and Vinorelbine. Knocking down F2R in GC cell lines resulted in slowed proliferation, migration, and invasion. All statistical analyses were performed using R software (version 4.2.1) and GraphPad Prism 9.0. p < 0.05 was considered statistically significant. In conclusion, this study underscores the significance of F2R as a potential biomarker in gastric adenocarcinoma, shedding light on its molecular mechanisms in tumorigenesis. F2R holds promise for aiding in the diagnosis, prognosis, and targeted therapy of STAD.

Oncological features and prognosis of colorectal cancer in human immunodeficiency virus-positive patients: A retrospective study.

Due to the prolonged life expectancy and increased risk of colorectal cancer (CRC) among patients with human immunodeficiency virus (HIV) infection, the prognosis and pathological features of CRC in HIV-positive patients require examination. To compare the differences in oncological features, surgical safety, and prognosis between patients with and without HIV infection who have CRC at the same tumor stage and site. In this retrospective study, we collected data from HIV-positive and -negative patients who underwent radical resection for CRC. Using random stratified sampling, 24 HIV-positive and 363 HIV-negative patients with colorectal adenocarcinoma after radical resection were selected. Using propensity score matching, we selected 72 patients, matched 1:2 (HIV-positive:negative = 24:48). Differences in basic characteristics, HIV acquisition, perioperative serological indicators, surgical safety, oncological features, and long-term prognosis were compared between the two groups. Fewer patients with HIV infection underwent chemotherapy compared to patients without. HIV-positive patients had fewer preoperative and postoperative leukocytes, fewer preoperative lymphocytes, lower carcinoembryonic antigen levels, more intraoperative blood loss, more metastatic lymph nodes, higher node stage, higher tumor node metastasis stage, shorter overall survival, and shorter progression-free survival compared to patients who were HIV-negative. Compared with CRC patients who are HIV-negative, patients with HIV infection have more metastatic lymph nodes and worse long-term survival after surgery. Standard treatment options for HIV-positive patients with CRC should be explored.

A biomimetic nanocarrier facilitates glucose consumption and reactive oxide species accumulation in enzyme therapy for colorectal cancer

Glucose oxidase (GOx)-based enzyme therapeutics are potential alternatives for colorectal cancer (CRC) treatment via glucose consumption and accumulation of hydrogen peroxide (H2O2). Given that H2O2 can be eliminated by cytoprotective autophagy, autophagy inhibitors that can interrupt autolysosome-induced H2O2 elimination are promising combination drugs of GOx. Here, we developed a multifunctional biomimetic nanocarrier for effective co-delivery of an autophagy inhibitor-chloroquine phosphate (CQP) and GOx to exert their synergistic effect by irreversibly upregulating intracellular reactive oxygen species (ROS) levels. Poly (D, l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) were used to encapsulate both GOx and CQP using a W/O/W multi-emulsion method. Calcium phosphate (CaP) was used to “fix” CQP to GOx in the internal water phase, where it served as a pH-sensitive unit to facilitate intracellular drug release. Folic acid-modified red blood cell membranes (FR) were used to camouflage the GOx/CQP/CaP encapsulated PLGA NPs (referred to as PLGA/GCC@FR). In an AOM/DSS-induced CRC mouse model, PLGA/GCC@FR exhibited improved antitumor effects, in which the number of tumor nodes were only a quarter of that in the free drug combination group. The enhanced therapeutic effects of PLGA/GCC@FR were attributed to the prolonged tumor retention which was verified by both dynamic in vivo imaging and drug biodistribution. This multifunctional biomimetic nanocarrier facilitated combined enzyme therapeutics by depleting glucose and augmenting intracellular ROS levels in tumor cells, which exerted a synergistic inhibitory effect on tumor growth. Therefore, this study proposed a novel strategy for the enhancement of combined enzyme therapeutics, which provided a promising method for effective CRC treatment.

Clinical value assessment for serum hsa_tsr013526 in the diagnosis of gastric carcinoma.

Gastric carcinoma (GC) is a malignant tumor that is detrimental to human health. Transfer RNA-derived small RNAs are a newly identified class of noncoding small RNAs with specific biological functions that are aberrantly expressed in cancer. The aim of this study was to investigate the potential of hsa_tsr013526 as a biomarker for GC. Quantitative real-time fluorescence polymerase chain reaction was used to detect the expression level of hsa_tsr013526. The molecular characteristics of hsa_tsr013526 were verified by agarose gel electrophoresis, Sanger sequencing, and separation of nuclear and cytoplasmic RNA fractions. By testing the receiver operating characteristic (ROC) curves, the diagnostic efficiency of GC using hsa_tsr013526 was determined. Finally, we predicted the downstream of hsa_tsr013526 using functional assays and bioinformatics analysis. Serum expression of hsa_tsr013526 was higher in GC patients than in healthy donors. Serum expression showed differential changes in GC patients, gastritis patients, and healthy donors. Chi-squared tests showed that high expression of hsa_tsr013526 was significantly correlated with T stage, lymphatic metastasis, and tumor node metastasis stage. ROC curve analysis indicated that GC patients could be discriminated from healthy donors or gastritis patients based on their serum levels of hsa_tsr013526. Furthermore, hsa_tsr013526 expression was significantly reduced in postoperative GC patients (p = .0016). High expression of hsa_tsr013526 promotes gastric cancer cell proliferation, invasion, and migration. Serum hsa_tsr013526 was stable and specific, and could be used for dynamic monitoring of GC patients. Therefore, hsa_tsr013526 may be a new biomarker for the diagnosis and postoperative monitoring of GC patients.

AZUR-2, a phase III, open-label, randomized study of perioperative dostarlimab monotherapy vs standard of care in previously untreated patients with T4N0 or stage III dMMR/MSI-H resectable colon cancer.

TPS240 Background: Emerging evidence suggests neoadjuvant therapy may benefit patients (pts) with advanced colon cancer. Neoadjuvant immunotherapy has shown promising efficacy for early-stage mismatch repair deficient (dMMR) colon cancer [1,2]. Evidence from other immunogenic tumors suggests that a perioperative approach with immunotherapy may further improve survival outcomes [3,4]. Dostarlimab (anti-PD-1) has shown a favorable benefit:risk profile in previously untreated dMMR locally advanced rectal cancer [5] and in advanced dMMR/microsatellite instability-high (MSI-H) solid tumors [6]. AZUR-2 (NCT05855200) will evaluate the efficacy and safety of perioperative dostarlimab monotherapy vs standard of care (SOC) in pts with previously untreated T4N0 or Stage III dMMR/MSI-H resectable colon adenocarcinoma. Methods: AZUR-2 is a global, multicenter, randomized, open-label Phase III study. Approximately 711 pts will be enrolled. Key eligibility criteria include age ≥18 years, no prior therapy or surgery for colon cancer, ECOG PS 0–1, and no symptomatic bowel obstruction. Central prescreening is available at sites without local dMMR/MSI-H testing (not required if dMMR/MSI-H already determined). Pts stratified by clinical tumor/node (TN) staging will be randomized 2:1 to receive dostarlimab pre- and post-surgery, or surgery followed by SOC (adjuvant FOLFOX/CAPEOX for 3–6 months or watch and wait approach per physician’s discretion). Primary endpoint is event-free survival (EFS) (events: recurrence based on radiological assessment by blinded independent central review or pathological assessment of new lesions, disease progression precluding surgery, treatment (tx)-related toxicity precluding surgery, or death). Secondary endpoints include pathological response, OS, and safety. Disease assessments will consist of CT scans of chest, abdomen, and pelvis. Pts will undergo safety follow-up at end of tx and at 30 and 90 days after last dose. Efficacy will be assessed in all pts randomized (intent-to-treat) and safety in all pts who receive surgery or ≥1 dose of study tx. A stratified log-rank test will be used for primary analysis. The primary analysis for EFS with &gt;90% power will be conducted after all pts have been followed for ≥3 years. An interim EFS analysis will be conducted ~12 months earlier. Exploratory endpoints include pt-reported outcomes to evaluate health-related quality of life.

Expanding immunotherapy options in cholangiocarcinoma: Role of CD27 agonist in combination with PD-L1 and MEK inhibition on antitumor effect and CD8+ T cells.

518 Background: Despite addition of PD-L1 therapy to unresectable cholangiocarcinoma (CCA) standard of care, there remains an unmet need for novel therapies. Our recent phase II trial of dual PD-L1 inhibition (PD-L1i) and MEK inhibition (MEKi) significantly improved progression-free survival (PFS). While MEKi enhances tumor antigen presentation and T cell tumor infiltration, it also impairs T cell priming and activation with notable CD27 upregulation. Our work reveals that CD27 agonists (CD27Ag) foster T cell stem-like and resident memory phenotypes, negating inhibitory effect of MEKi on CD8+ T cells. We hypothesized that addition of a CD27Ag to PD-L1i/MEKi combination therapy would rescue T cell activation and improve antitumor efficacy. Methods: Immune cells from pmel-1 mice were isolated, activated with gp100, and cultured in vitro with 100 IU/mL IL-2 and single, dual, or triple therapy with CD27Ag, cobimetinib (MEKi) and/or αPD-L1. Day 3 flow cytometry characterized CD8+ T cell phenotype and cytokine expression. Additionally, syngeneic murine CCA cell line URCCA4.3 (KrasG21D, tp53-/-) was injected into C57BL/6 mice, subcutaneously or intrahepatic, followed by ~3 weeks of treatment with mono, dual, or triple therapy. For CD8 depletion studies, CD8-depleting antibody was given on the day prior to and following surgery and every 3-4 days afterwards. Tumor and tumor-draining lymph nodes were harvested at study endpoint. Lymphocytes were characterized by flow cytometry. Results: MEKi, alone or with αPD-L1, reduced frequency of activated T cells in vitro (dose-dependent effect on CD69+). CD27Ag combined with MEKi maintained prominent T cell activation. Triple therapy PD-L1i/MEKi/CD27Ag significantly reduced tumor growth rate in mice versus mono or dual therapies (p&lt;0.05). Tumor-infiltrating lymphocytes comprised a stem-like (Tcf-1+), effector memory (CD44+CD62L-), and tissue resident memory (CD103+CD69+) phenotype in triple therapy versus single or dual therapy (p&lt;0.01, p&lt;0.0001, p&lt;0.0001 respectively). All groups had similar numbers of CD8+ stem-like cells (Tcf-1+Tim-3-) in draining lymph nodes, but these cells were only present in tumor from the triple therapy arm (p&lt;0.05). Cell depletion studies showed that CD8+ T cells were required for efficacy of triple therapy in vivo. Finally, an aggressive orthotopic liver tumor model showed improved median survival in triple therapy mice versus control (37.5 days versus 29.5 days, p&lt;0.01). Conclusions: CD27 agonism prevents the impairment of T cell activation that was mediated by MEKi. Moreover, this CD27Ag/MEKi/PDL1i triple therapy bolstered trafficking of T cells with stem-like, effector, or resident memory properties, in turn enhancing the antitumor response. This therapy is being evaluated in metastatic CCA patients in an ongoing Phase II clinical trial.

Nomograms predict survival in elderly women with triple-negative breast cancer: A SEER population-based study.

The effective treatment of breast cancer in elderly patients remains a major challenge. To construct a nomogram affecting the overall survival of triple-negative breast cancer (TNBC) and establish a survival risk prediction model. A total of 5317 TPBC patients with negative expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) who were diagnosed and received systematic treatment from 2010 to 2015 were collected from the American Cancer Surveillance, Epidemiology and End Results (SEER) database. They were randomly divided into training set (n= 3721) and validation set (n= 1596). Univariate and multivariate Cox regression analysis were used to identify prognostic features, and a nomogram was established to predict the probability of 1-year, 3-year and 5-year OS and BCSS. We used consistency index (C-index), calibration curve, area under the curve (AUC) and decision curve analysis (DCA) to evaluate the predictive performance and clinical utility of the nomogram. The C-indices of the nomograms for OS and BCSS in the training cohort were 0.797 and 0.825, respectively, whereas those in the validation cohort were 0.795 and 0.818, respectively. The receiver operating characteristic (ROC) curves had higher sensitivity at all specificity values as compared with the Tumor Node Metastasis (TNM) system. The calibration plot revealed a satisfactory relationship between survival rates and predicted outcomes in both the training and validation cohorts. DCA demonstrated that the nomogram had clinical utility when compared with the TNM staging system. This study provides information on population-based clinical characteristics and prognostic factors for patients with triple-negative breast cancer, and constructs a reliable and accurate prognostic nomogram.