We asked what preoperative radiotherapy/chemoradiotherapy (PRT/PCRT) has brought to patients in terms of perioperative and long‐term outcomes over the past decades. A systematic review and meta‐analysis was conducted using PubMed, Embase and Web of Science databases. All original comparative studies published in English that were related to PRT/PCRT and surgical resection and which analyzed survival, postoperative and quality of life outcomes were included. Data synthesis and statistical analysis were carried out using Stata software. Data from 106 comparative studies based on 80 different trials enrolling 41,121 patients were included in our study. Based on our overall analyses, PRT/PCRT significantly improved patients' local recurrence‐free survival (LRFS), but neither overall survival (OS) nor metastasis‐free survival (MFS) showed improvement. In addition, PRT significantly increased the postoperative morbidity and mortality but PCRT did not have a significant effect. Furthermore, PRT/PCRT significantly increased the risk of postoperative wound complications but not anastomotic leakage and bowel obstruction. Our comprehensive subgroup analyses further supported the aforementioned results. Meanwhile, long‐term anorectal symptoms (impaired squeeze pressures, use of pads, incontinence and urgency) and erectile dysfunction were also significantly increased in patients after PRT/PCRT. The benefits of PRT/PCRT as applied over the last several decades have not been sufficient to improve OS. Metastases of primary tumor and postoperative adverse effects were the two primary obstacles for an improved OS. In fact, the greatest advantage of PRT/PCRT is still local tumor control and a significantly improved LRFS.

The gut microbiota plays a critical role in the anti-tumor immune response. There is increasing data showing that antibiotics (ATBs) change the composition of the gut microbiota and affect the efficacy of immune checkpoint inhibitors (ICIs). However, this is the first meta-analysis to evaluate the association between ATB use and ICI efficacy in cancer patients to provide a better understanding of the strength of this association. We performed a literature search for relevant studies that evaluated the relationship between ATB use and ICI efficacy using the PubMed, Embase, and conference databases. The primary outcomes consisted of overall survival (OS) and progression-free survival (PFS) measured by hazard ratios (HR) and corresponding 95% confidence intervals (CI). Subgroup and sensitivity analyses were also performed. A total of 19 eligible studies comprising 2,740 cancer patients treated with ICIs were included in the analysis. Our results indicated that ATB use was negatively associated with OS in cancer patients (HR = 2.37; 95% CI = 2.05–2.75; P < .001), without heterogeneity (I² = 0.0%; P = .851). Moreover, ATB use significantly reduced PFS in patients treated with ICIs (HR = 1.84; 95% CI = 1.49–2.26; P < .001; I² = 56.2%). Similar results were obtained in the subgroup analyses stratified by the time of ATB use and cancer type. Sensitivity analyses confirmed the stability of our results. Therefore, the findings of our meta-analysis indicated that ATB use is negatively associated with OS and PFS in cancer patients treated with ICI immunotherapy.

The prognostic value of circulating tumor cells (CTCs) detected with the CellSearch System in patients with colorectal cancer (CRC) is controversial. The aim of our meta-analysis was to evaluate whether the detection of CTCs in the peripheral blood with the standardized CellSearch System has prognostic utility for patients with CRC. The PubMed, Science Citation Index, Cochrane Database, Embase, and the references in relevant studies were systematically searched (up to December, 2014). No search restrictions were imposed. Our meta-analysis was performed in Stata software, version 12.0 (2011) (Stata Corp, College Station, TX, USA), with the odds ratio (OR), risk ratio (RR), hazard ratio (HR), and 95% confidence interval (95% CI) as the effect measures. Subgroup and sensitivity analyses were also conducted. Eleven studies containing 1847 patients with CRC were analyzed. There was a significantly higher incidence of CTCs in the metastasis-positive group than in the metastasis-negative group (OR = 4.06, 95% CI [1.74, 9.50], P < 0.01, I2 = 0%). For hepatic metastasis, a type of metastasis, a higher incidence of CTCs was observed in the hepatic-metastasis-positive group than in the -negative group (OR = 2.61, 95% CI [1.73, 3.96], P < 0.01, I2 = 0%). The presence of CTCs was significantly related to overall survival (HR = 2.00, 95% CI [1.49, 2.69], P < 0.01, I2 = 67.1%) and progression-free survival (HR = 1.80, 95% CI [1.52, 2.13], P < 0.01, I2 = 43.9%) of patients with CRC, regardless of the sampling time. The response rate for the CTC+ groups was significantly lower than that for the CTC− groups at baseline and during treatment (baseline: 33% versus 39%, RR = 0.79, 95% CI [0.63, 0.99], P = 0.04, I2 = 7.0%; during treatment: 17% versus 46%, RR = 0.41, 95% CI [0.22, 0.77], P = 0.01, I2 = 0.0%;). Our meta-analysis indicates that the detection of CTCs in the peripheral blood with the CellSearch System has prognostic utility for patients with CRC.

Peritoneal metastasis is the leading cause of death for gastrointestinal cancers. The native and therapy-induced ascites ecosystems are not fully understood. Here, we characterize single-cell transcriptomes of 191,987 ascites cancer/immune cells from 35 patients with/without gastric cancer peritoneal metastasis (GCPM). During GCPM progression, an increase is seen of monocyte-like dendritic cells (DCs) that are pro-angiogenic with reduced antigen-presenting capacity and correlate with poor gastric cancer (GC) prognosis. We also describe the evolution of monocyte-like DCs and regulatory and proliferative T cells following therapy. Moreover, we track GC evolution, identifying high-plasticity GC clusters that exhibit a propensity to shift to a high-proliferative phenotype. Transitions occur via the recently described, autophagy-dependent plasticity program, paligenosis. Two autophagy-related genes (MARCKS and TXNIP) mark high-plasticity GC with poorer prognosis, and autophagy inhibitors induce apoptosis in patient-derived organoids. Our findings provide insights into the developmental trajectories of cancer/immune cells underlying GCPM progression and therapy resistance.

The prognostic role of neutrophil to lymphocyte ratio (NLR) in gastric cancer remains controversial. We aimed to quantify the prognostic role of peripheral blood NLR in gastric cancer. A literature search was conducted in PubMed, EMBASE, and Cochrane databases. The results for overall survival (OS) and progression-free survival (PFS)/disease-free survival (DFS) are expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). 19 studies with 5431 patients were eligible for final analysis. Elevated NLRs were associated with a significantly poor outcome for OS (HR = 1.98; 95% CI: 1.75–2.24,p<0.001) and PFS (HR = 1.58; 95% CI: 1.32–1.88,p<0.001) compared with patients who had normal NLRs. The NLR was higher for patients with late-stage compared with early-stage gastric cancer (OR = 2.76; 95% CI: 1.36–5.61,p=0.005). NLR lost its predictive role for patients with stage IV gastric cancer who received palliative surgery (HR = 1.73; 95% CI: 0.85–3.54,p=0.13). Our results also indicated that prognoses might be influenced by the NLR cutoff values. In conclusion, elevated pretreatment NLRs are associated with poor outcome for patients with gastric cancer. The ability to use the NLR to evaluate the status of patients may be used in the future for personalized cancer care.