The loss of skeletal muscle mass and function is defined as sarcopenia, which might develop in elderly patients with cancers. It has been indicated as a potential negative factor in the survival of patients with malignant tumours. The aim of this systematic review and meta-analysis was to evaluate the associations between sarcopenia and survival outcomes or postoperative complications in patients with oesophageal cancer (EC). Web of Science, Embase, Medline, and Cochrane Library databases were searched until 10 May 2022, using keywords: sarcopenia, oesophageal cancer, and prognosis. Studies investigating the prognostic value of sarcopenia on EC survival were included. Forest plots and summary effect models were used to show the result of this meta-analysis. The quality of included studies was evaluated with the Newcastle-Ottawa Scale (NOS). A total of 1436 studies were identified from the initial search of four databases, and 41 studies were included for the final quantitative analysis. This meta-analysis revealed a significant association between sarcopenia and overall survival (OS) [hazard ratios (HR):1.68, 95% confidence interval (CI):1.54-1.83, P = 0.004, I 2 = 41.7%] or disease-free survival (DFS) 1.97 (HR: 1.97, 95% CI: 1.44-2.69, P = 0.007, I 2 = 61.9%) of EC patients. Subgroup analysis showed that sarcopenia remained a consistent negative predictor of survival when stratified by different treatment methods, populations, or sarcopenia measurements. Sarcopenia was also a risk factor for postoperative complications with a pooled odds ratio of 1.47 (95% CI: 1.21-1.77, P = 0.094, I 2 = 32.7%). The NOS scores of all included studies were ≥6, and the quality of the evidence was relatively high. The results from the study suggested that sarcopenia was significantly associated with both survival outcomes and postoperative complications in EC patients. Sarcopenia should be appropriately diagnosed and treated for improving short-term and long-term outcomes of patients with EC.

Radiotherapy and chemotherapy are limited by insufficient therapeutic efficacy of low‐dose radiation and nonspecific drug biodistribution. Herein, an acid‐responsive aggregated nanosystem (AuNPs‐D‐P‐DA) loaded with doxorubicin (DOX) is designed for radiosensitization and synergistic chemoradiotherapy. In response to the acid microenvironment of esophageal cancer (EC), small‐sized AuNPs‐D‐P‐DA forms large‐sized gold nanoparticle (AuNPs) aggregates in tumor tissues to hinder the backflow of AuNPs to the circulation, resulting in enhanced tumor accumulation and retention. Simultaneously, the AuNPs‐based radiosensitization is significantly improved because of the high concentration and large size of intratumoral AuNPs, while DOX are delivered and released specifically into tumor cells triggered by the acid microenvironment for chemo‐radio synergistic therapy. Acid‐responsive AuNPs exacerbate radiation‐induced DNA damage, cell apoptosis, cell cycle arrest, and low colony formation ability in vitro and enhance anti‐tumor efficacy in vivo compared to un‐responsive control. When combined with acid‐responsive DOX, the therapeutic efficacy of the formulation is further improved by their synergistic effect. After the treatment of acid‐responsive AuNPs plus radiotherapy, fatty acid metabolism is reprogrammed in xenograft models, which provides potential targets for further improvement of radiosensitization. In summary, the acid‐responsive AuNPs‐D‐P‐DA nanosystem leverages the radio‐ and chemotherapeutic synergies of AuNPs‐sensitized X‐ray irradiation and acid‐responsive DOX in the treatment of EC.

Esophageal cancer (EC) is a common malignant gastrointestinal (GI) cancer in adults. Although surgical technology combined with neoadjuvant chemoradiotherapy has advanced rapidly, patients with EC are often diagnosed at an advanced stage and the five-year survival rate remains unsatisfactory. The poor prognosis and high mortality in patients with EC indicate that effective and validated therapy is of great necessity. Recently, immunotherapy has been successfully used in the clinic as a novel therapy for treating solid tumors, bringing new hope to cancer patients. Several immunotherapies, such as immune checkpoint inhibitors (ICIs), chimeric antigen receptor T-cell therapy, and tumor vaccines, have achieved significant breakthroughs in EC treatment. However, the overall response rate (ORR) of immunotherapy in patients with EC is lower than 30%, and most patients initially treated with immunotherapy are likely to develop acquired resistance (AR) over time. Immunosuppression greatly weakens the durability and efficiency of immunotherapy. Because of the heterogeneity within the immune microenvironment and the highly disparate oncological characteristics in different EC individuals, the exact mechanism of immunotherapy resistance in EC remains elusive. In this review, we provide an overview of immunotherapy resistance in EC, mainly focusing on current immunotherapies and potential molecular mechanisms underlying immunosuppression and drug resistance in immunotherapy. Additionally, we discuss prospective biomarkers and novel methods for enhancing the effect of immunotherapy to provide a clear insight into EC immunotherapy.

BackgroundThe Geriatric Nutritional Index (GNRI) has been indicated as a nutritional index which is highly associated with complications and mortality in older hospitalized patients. Moreover, early studies had suggested that GNRI is a potential prognostic indicator for some malignances. However, the prognostic value of GNRI in esophageal squamous cell carcinoma (ESCC) patients underwent neoadjuvant therapy followed by esophagectomy remains elusive.Materials and methodsThis retrospective study incorporated 373 patients with ESCC who had underwent neoadjuvant therapy followed by radical esophagectomy at West China Hospital of Sichuan University between April 2011 and September 2021. The GNRI formula was: 1.489 × albumin (g/dl) + 41.7 × current weight/ideal weight. Patients were classified as GNRI-low (GNRI < 98.7) or GNRI high (GNRI ≥ 98.7). The association between GNRI and clinical survival status were assessed utilizing Kaplan-Meier methods and Cox regression analysis.ResultsThree hundred and seventy three patients were retrospectively included in this study. 80 (21.5%) and 293 (78.5%) patients had been divided into the GNRI-low and GNRI-high groups respectively. Pathological T stage and the rate of nodal metastasis were significantly higher in the GNRI low group than in the GNRI high group (P = 0.003 and P = 0.001, respectively) among the examined demographic parameters. Furthermore, GNRI was significantly correlated with postoperative complications, patients with lower GNRI had a higher postoperative complication rate as compared with GNRI high group [Odds ratio: 2.023; 95% confidence interval (CI): 1.208–3.389; P = 0.007]. Univariate analysis of 5-year overall survival (OS) and disease-free survival (DFS) found that the rate of survival was considerably lower in the GNRI-low group than in the GNRI-high group (P < 0.001). However, multivariate analysis demonstrated that GNRI was not an independent risk factor.ConclusionIn patients with ESCC, low GNRI exhibited a poor nutritional indicator and related to postoperative complications after neoadjuvant therapy. Intensive follow-up after surgery should be performed for ESCC patients with low GNRI.

Objectives To evaluate the short-term outcomes of neoadjuvant chemoimmunotherapy followed by oesophagectomy for locally advanced oesophageal squamous carcinoma. Methods Patients receiving neoadjuvant chemoimmunotherapy or chemoradiotherapy between September 2019 and September 2021 were identified. The primary outcomes were tumour response and survival. Secondary outcomes were toxic effects and postoperative complications. The propensity score matching for enrolled patients was performed. Results Data of 149 patients with clinical stage II-IV oesophageal squamous cancer, including 55 receiving neoadjuvant chemoimmunotherapy and 94 receiving neoadjuvant chemoradiotherapy, were analyzed after propensity score matching. With regard to tumour response score, 24 (43.6%) and 59 (62.8%) patients were scored 0/1 in the neoadjuvant chemoimmunotherapy and neoadjuvant chemoradiotherapy groups, respectively (p = 0.023). Of note, 17 (30.9%) patients in the neoadjuvant chemoimmunotherapy group achieved pathological complete response (ypT0N0), while 48 (51.1%) patients in neoadjuvant chemoradiotherapy group achieved pathological complete response (P = 0.026). Neoadjuvant chemoradiotherapy was associated with higher risk of postoperative pneumonia (p = 0.034) and less lymph nodes and stations dissected (p ≤ 0.001). The 1-year cumulative overall survival rate was 94.5% and 86.2% in the NACI and NACR groups, respectively (p = 0.170). Conclusions We found that neoadjuvant chemoimmunotherapy compared with neoadjuvant chemoradiotherapy was associated with lower pneumonia rate and was safe and feasible for locally advanced oesophageal squamous cancer. However, the tumour regression score and the pathological complete response rate of patients treated with neoadjuvant immunotherapy was lower than those of patients treated with neoadjuvant chemoradiotherapy. The short-term follow-up results were comparable between two treatment modalities.

Background: The aim of this study was to determine the role of adjuvant therapy after neoadjuvant chemoradiotherapy and esophagectomy for esophageal squamous cell carcinoma (ESCC). Methods: The study retrospectively reviewed 447 ESCC patients who underwent neoadjuvant chemoradiotherapy and esophagectomy. Patients were divided into an adjuvant therapy group and no adjuvant therapy group. Propensity score matching was used to adjust the confounding factors. Results: 447 patients with clinical positive lymph nodes and no distant metastasis treated with neoadjuvant chemoradiotherapy and esophagectomy were eligible for analysis. After propensity score matching, there were 120 patients remaining in each group. Patients receiving adjuvant therapy had a significantly shorter post-resection overall survival (OS) and disease-free survival (DFS) when compared to patients not receiving adjuvant therapy (log-rank, OS: p = 0.046, DFS: p < 0.001). Receiving adjuvant therapy is not an independently prognostic factor for OS (hazard ratio (HR): 1.270, HR: 0.846–1.906, p = 0.249) but a significantly unfavorable independent prognostic factor for DFS (HR: 2.061, HR: 1.436–2.958, p < 0.001). Conclusions: The results of our study indicate that adjuvant therapy after neoadjuvant chemoradiotherapy and surgery could reduce the OS and DFS in patients with ESCC. Therefore, adjuvant therapy is not recommended for ESCC patients after neoadjuvant chemoradiotherapy and esophagectomy, especially patients without nodal metastases after neoadjuvant therapy.

Esophageal cancer (EC) is one of the most common cancers worldwide. Malnutrition often leads to poor prognosis of patients with EC. Geriatric nutritional risk index (GNRI) was reported as an objective nutrition-related risk index. We intend to comprehensively review evidence of GNRI in predicting EC prognosis. To explore the influence of GNRI on the long-term survival outcome of patients with EC, a meta-analysis was needed. We searched the Web of Science, Medline, Embase, and the Cochrane Library databases. The association between prognosis of patients with EC and GNRI was evaluated by pooling hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs). The fixed model or random model method was chosen according to the heterogeneity among the studies. Totally, 11 studies with 1785 patients who met the inclusion criteria were eventually included in our meta-analysis. Comparing the lower level GNRI group and the higher level GNRI group, the pooled results showed that lower GNRI had a negative impact on overall survival (OS) (HR: 1.75, 95% CI: 1.45–2.10, P &lt; 0.01) and cancer-specific survival (CSS) (HR: 1.77, 95% CI: 1.19–2.62, P &lt; 0.01), indicating that lower GNRI significantly predicted poor OS. In conclusion, lower GNRI could predict the poor prognosis of patients with EC. Meanwhile, more well-designed randomized controlled trials (RCTs) are needed to confirm the findings.

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