Postoperative Adjuvant Chemotherapy Cancel Out the Negative Survival Impact on Stage II/III Gastric Cancer Patients With Postoperative Complications

Purpose The potential additive influence of adjuvant chemotherapy (AC) on prognosis of patients with stage II/III gastric cancer (GC) who experienced complications after radical surgery is unclear.Methods The whole group was divided into a postoperative complication (PC) group and a postoperative non-complication (NPC) group, and the overall survival (OS) rate, recurrence-free survival (RFS) rate and recurrence rate were compared between the two groups of patients. Results A total of 1563 patients between January 2010 and December 2015 in our center were included in this analysis. There were 268 patients (17.14%) in the PC group and 1295 patients (82.86%) in the NPC group. The 5-year OS rate of the PC group was 55.2%, the NPC group was 63.3%; and the 5-year RFS rate of the PC group was 53.7%, the non-PC group was 58.8%. Recurrence patterns showed no significant difference between the two group (all p>0.05). Adjuvant chemotherapy (AC) significantly improved the OS and RFS rates of patients with and without PCs (both p<0.05), and it showed no significant difference between the PC group and the NPC group who received AC (both p> 0.05). Stratified analysis showed that AC only improve the OS or RFS rates of stage III patients (both p<0.05). Further stratified analysis of the time interval (TI) from operation to initiation of AC in the PC group showed that a TI after 6 weeks (≥6eeks) improved only the OS and RFS rates of stage III patients, while when a TI within 6 weeks (＜6weeks), a benefit was observed in stage II and III patients (both p<0.05).Conclusion AC can abolish the negative effect of PCs on the long-term survival of patients with stage III GC; for stage II patients, the above offset effect is affected by the TI. Delaying AC initiation after 6 weeks may not improve the survival of patients experienced stage II GC with complications.

Senescence as a dictator of patient outcomes and therapeutic efficacies in human gastric cancer

Senescence is believed to be a pivotal player in the onset and progression of tumors as well as cancer therapy. However, the guiding roles of senescence in clinical outcomes and therapy selection for patients with cancer remain obscure, largely due to the absence of a feasible senescence signature. Here, by integrative analysis of single cell and bulk transcriptome data from multiple datasets of gastric cancer patients, we uncovered senescence as a veiled tumor feature characterized by senescence gene signature enriched, unexpectedly, in the noncancerous cells, and further identified two distinct senescence-associated subtypes based on the unsupervised clustering. Patients with the senescence subtype had higher tumor mutation loads and better prognosis as compared with the aggressive subtype. By the machine learning, we constructed a scoring system termed as senescore based on six signature genes: ADH1B, IL1A, SERPINE1, SPARC, EZH2, and TNFAIP2. Higher senescore demonstrated robustly predictive capability for longer overall and recurrence-free survival in 2290 gastric cancer samples, which was independently validated by the multiplex staining analysis of gastric cancer samples on the tissue microarray. Remarkably, the senescore signature served as a reliable predictor of chemotherapeutic and immunotherapeutic efficacies, with high-senescore patients benefited from immunotherapy, while low-senescore patients were responsive to chemotherapy. Collectively, we report senescence as a heretofore unrecognized hallmark of gastric cancer that impacts patient outcomes and therapeutic efficacy.

Pretreatment Contrast-Enhanced Computed Tomography Radiomics for Prediction of Pathological Regression Following Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer: A Preliminary Multicenter Study

BackgroundSensitivity to neoadjuvant chemotherapy in locally advanced gastric cancer patients varies; however, an effective predictive marker is currently lacking. We aimed to propose and validate a practical treatment efficacy prediction method based on contrast-enhanced computed tomography (CECT) radiomics.MethodData of l24 locally advanced gastric carcinoma patients who underwent neoadjuvant chemotherapy were acquired retrospectively between December 2012 and August 2020 from three different cancer centers. In total, 1216 radiomics features were initially extracted from each lesion’s pretreatment portal venous phase computed tomography image. Subsequently, a radiomics predictive model was constructed using machine learning software. Clinicopathological data and radiological parameters of the enrolled patients were collected and analyzed retrospectively. Univariate and multivariate logistic regression analyses were performed to screen for independent predictive indices. Finally, we developed an integrated model combining clinicopathological predictive parameters and radiomics features.ResultIn the training set, 10 (14.9%) patients achieved a good response (GR) after preoperative neoadjuvant chemotherapy (n = 77), whereas in the testing set, seven (17.5%) patients achieved a GR (n = 47). The radiomics predictive model showed competitive prediction efficacy in both the training and independent external validation sets. The areas under the curve (AUC) values were 0.827 (95% confidence interval [CI]: 0.609–1.000) and 0.854 (95% CI: 0.610–1.000), respectively. Similarly, when only the single hospital data were included as an independent external validation set (testing set 2), AUC values of the models were 0.827 (95% CI: 0.650–0.952) and 0.889 (95% CI: 0.663–1.000) in the training set and testing set 2, respectively.ConclusionOur study is the first to discover that CECT radiomics could provide powerful and consistent predictions of therapeutic sensitivity to neoadjuvant chemotherapy among gastric cancer patients across different hospitals.

The Diagnostic and Prognostic Value of BEN-Domain (BEND) Family Genes in Gastric Cancer

BEND(BEN domain-containing protein)is a domain protein-coding gene, whose abnormal expression is related to the occurrence of malignant tumors. But studies on gastric cancer are rare. We attempted to investigate the role of BEND family genes in evaluating the prognosis of gastric cancer and guiding clinical treatment. We analyzed the BEND family genes expression, prognostic value, and drug sensitivity in pan-cancer, and the correlation between their expression and tumor microenvironment of gastric cancer, stemness index, immune subtypes, and clinicopathological characteristics were analyzed. We constructed a model using BEND3P1 and BEND6 to evaluate the prognosis of gastric cancer patients. Multivariate Cox proportional risk model analysis showed that risk score is an independent risk factor for gastric cancer patients. To assess the value of risk score for prognosis, patients were divided into high-risk and low-risk groups based on median risk scores, and survival analyses were performed. The results showed that the OS of patients with high-risk scores is significantly lower. We also constructed a nomogram to predict individual survival probability using the BEND risk score and clinical case characteristics. In conclusion, the BEND family genes can predict the prognosis and guide the treatment of gastric cancer patients.

OncoVee™-MiniPDX-Guided Anticancer Treatment for Gastric Cancer Patients With Synchronous Liver Metastases: A Retrospective Cohort Analysis

BackgroundIt is estimated that 35% of gastric cancer patients appear with synchronous distant metastases—the vast majority of patients presenting with metastatic hepatic disease. How to choose the most appropriate drugs or regimens is crucial to improve the prognosis of patients. We conducted this retrospective cohort analysis to evaluate the efficacy of OncoVee™-MiniPDX-guided treatment for these patients.MethodsGastric cancer patients with liver metastases (GCLM) were enrolled. Patients were divided into MiniPDX and control group according to their wishes. In the observation group, the OncoVee™-MiniPDX model was conducted to screen the most sensitive drug or regimens to determine the clinical administration. Meanwhile, patients were treated with regular medications in the control group according to the guidelines without the MiniPDX model. The primary endpoint was overall survival (OS), and the secondary outcomes included objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS).ResultsA total of 68 patients with GCLM were included, with the observation and control groups of 21 and 47 patients, respectively. The baseline characteristics of patients were balanced between these two groups. MiniPDX drug sensitivity tests were associated with the increased use of targeted drugs when compared with the control group (33.3 vs. 0%, p=0.032). Median OS was estimated to be 9.4 (95% CI, 7.9–11.2) months and 7.9 (95% CI, 7.2–8.7) months in the observation and control group, respectively. Both univariate (control group vs. MiniPDX group: HR=2.586, 95% CI= 1.362–4.908, p=0.004) and multivariate regression analyses (Control group vs. MiniPDX group: adjusted HR (aHR)=4.288, 95% CI= 1.452–12.671, p=0.008) showed the superiority of the observation group on OS. Similarly, MiniPDX-based regiments significantly improve the PFS of these cases (median PFS 6.7 months vs. 4.2 months, aHR=2.773, 95% CI=1.532–3.983, p=0.029). ORR and DCR were also improved in MiniPDX group comparing with control group (ORR, 57.14 vs. 25.53%, p=0.029; DCR: 85.71 vs. 68.08%, p=0.035).ConclusionOncoVee™-MiniPDX model, which was used to select drugs to guide antitumor treatment, was promising to prolong survival and improve the response rate of patients with GCLM. Further well-designed studies are needed to confirm the clinical benefits of MiniPDX.