Summary Background Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy. Methods To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs). Findings Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37 298 (93%) of 40 070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28·0% vs 31·4%; RR 0·86, 95% CI 0·82–0·89; p<0·0001). 10-year breast cancer mortality was similarly reduced (18·9% vs 21·3%; RR 0·87, 95% CI 0·83–0·92; p<0·0001), as was all-cause mortality (22·1% vs 24·8%; RR 0·87, 95% CI 0·83–0·91; p<0·0001). Death without recurrence was, if anything, lower with dose-intense than with standard-schedule chemotherapy (10-year risk 4·1% vs 4·6%; RR 0·88, 95% CI 0·78–0·99; p=0·034). Recurrence reductions were similar in the seven trials (n=10 004) that compared 2-weekly chemotherapy with the same chemotherapy given 3-weekly (10-year risk 24·0% vs 28·3%; RR 0·83, 95% CI 0·76–0·91; p<0·0001), in the six trials (n=11 028) of sequential versus concurrent anthracycline plus taxane chemotherapy (28·1% vs 31·3%; RR 0·87, 95% CI 0·80–0·94; p=0·0006), and in the six trials (n=6532) testing both shorter intervals and sequential administration (30·4% vs 35·0%; RR 0·82, 95% CI 0·74–0·90; p<0·0001). The proportional reductions in recurrence with dose-intense chemotherapy were similar and highly significant (p<0·0001) in oestrogen receptor (ER)-positive and ER-negative disease and did not differ significantly by other patient or tumour characteristics. Interpretation Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrentl...
Gastric cancer is the fourth leading cause of cancer-related mortality across the globe, with a 5-year survival rate of less than 40%. In recent years, several applications of artificial intelligence (AI) have emerged in the gastric cancer field based on its efficient computational power and learning capacities, such as image-based diagnosis and prognosis prediction. AI-assisted diagnosis includes pathology, endoscopy, and computerized tomography, while researchers in the prognosis circle focus on recurrence, metastasis, and survival prediction. In this review, a comprehensive literature search was performed on articles published up to April 2020 from the databases of PubMed, Embase, Web of Science, and the Cochrane Library. Thereby the current status of AI-applications was systematically summarized in gastric cancer. Moreover, future directions that target this field were also analyzed to overcome the risk of overfitting AI models and enhance their accuracy as well as the applicability in clinical practice.
Background: Gastric cancer remains the third most common cause of cancer-related death worldwide. The development of novel therapeutic strategies for gastric cancer requires a deep understanding of the tumor cells and microenvironment of gastric cancer. Methods: We performed the single-cell RNA sequencing (scRNA-seq) on nine untreated non-metastatic gastric cancer patients. The transcriptomic atlas and ligand-receptor-based intercellular communication networks of the single cells were characterized. Results: Here, we profiled the transcriptomes of 47,304 cells from nine patients with gastric cancer. Tregs cells were significantly enriched in the gastric tumor tissues with increased expression of immune suppression related genes, which suggest a more immunosuppressive microenvironment. We also observed the absence of separate exhausted CD8+ T cell cluster, and the low expression level of exhaustion markers PDCD1, CTLA4, HAVCR2, LAG-3, and TIGIT in those specific cells. These may serve as molecular-level evidence for the limited benefit of immunotherapy among gastric cancer patients. In addition, we found ACKR1 specifically expressed in tumor endothelial cells, associated with poor prognosis in the cohort data and potentially provided a novel target of gastric cancer treatment. Furthermore, the tight interaction between endothelial cells and fibroblast implied the important roles of fibroblast in tumor angiogenesis and the maintenance of tumor vasculature. Conclusions:In conclusion, this single-cell atlas provide understanding the cellular heterogeneity from molecular level in gastric cancer and will serve as a valuable resource for developing innovative early and companion diagnostics, as well as discovering novel targeted therapies for gastric cancer.
The aim of the present study was to compare the short-term and long-term survival outcomes of laparoscopic gastrectomy vs. open gastrectomy in treating locally advanced gastric cancer (LAGC) after neoadjuvant therapy. This study retrospectively reviewed the medical records of 270 patients with LAGC, who underwent laparoscopic (n=49) or conventional open (n=221) surgery following neoadjuvant therapy between January 2007 and December 2016 in China National Cancer Center. Postoperative parameters and survival outcomes including overall survival and disease-free survival were analyzed. Patients who underwent laparoscopic gastrectomy (LP) had significantly shorter postoperative stay and a decreased number of metastatic lymph nodes harvested compared to those who underwent open surgery. The 75% disease-free survival (DFS) time in the laparoscopic surgery group (25.7 months) was higher compared with the open surgery group (15.6 months). However, no significant difference was observed in 5-year overall survival and DFS between the two groups. In conclusion, LG provides non-inferior shortand long-term survival outcomes compared with open surgery, suggesting a laparoscopic approach may be justified for patients with LAGC receiving neoadjuvant therapy. More randomized controlled trials are required to investigate the positive effects of LG for LAGC following neoadjuvant therapy.
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