Induction sintilimab and chemotherapy followed by concurrent chemoradiotherapy for locally advanced esophageal cancer: a proof-of-concept, single-arm, multicenter, phase 2 trial.

Background: Concurrent chemoradiotherapy is the standard nonoperative treatment for locally advanced esophageal squamous cell carcinoma. However, local recurrence is still the main failure pattern, accounting for more than half of all treatment failures, indicating that the sensitivity of radiotherapy still needs to be improved. This trial aimed at demonstrating whether PD-1 inhibitors followed by chemoradiotherapy could promote esophageal tumor vascular normalization, alleviate hypoxia, and thus enhance radiosensitivity and improve local control. Methods: We did a multicenter, single-arm, phase 2 trial in China. Patients with locally advanced esophageal cancer were enrolled in this study. In induction phase, patients received two cycles of sintilimab, paclitaxel and carboplatin once per 21 days. In concurrent phase, patients were treated with five cycles of carboplatin and paclitaxel once per week concurrent with radiotherapy of 50.4Gy delivered in 28 fractions. The primary endpoint was 2-year local control rate. Hypoxia and vessel normalization was assessed before and after induction phase using immunofluorescence and perfusion CT. This trial is registered with ClinicalTrials.gov (NCT03985046). Findings: Seventy-five patients with esophageal cancer were enrolled in this study between October 2019 and April 2021. The median follow-up of surviving patients was 33.6 months (IQR 29.3-35.7). The 2-year local control rate was 81.7% (95% confidence interval, 72.7%-90.7%), which was much higher than that in concurrent chemoradiation only (71.3%) in previous studies. Vascular normalization and hypoxia alleviation were observed in both biopsy specimens and perfusion CT. Interpretation: The addition of induction immunotherapy to standard concurrent chemoradiotherapy could improve radiosensitivity for locally advanced esophageal cancer as non-surgical treatment. New treatment combination led to higher local control rate through promoting vascular normalization and alleviating hypoxia. Our findings suggest that induction immunotherapy followed by concurrent chemoradiotherapy could be a potential option in future treatment. Funding: National Natural Science Foundation of China and Shanghai Rising-Star Program.

Systemic therapy with or without local intervention for oligometastatic oesophageal squamous cell carcinoma (ESO-Shanghai 13): an open-label, randomised, phase 2 trial.

BACKGROUND: The efficacy of local therapy for patients with oligometastatic oesophageal squamous cell carcinoma is unclear. We aimed to assess the efficacy of local plus systemic therapy compared with systemic therapy alone in patients with oligometastatic oesophageal squamous cell carcinoma. METHODS: The ESO-Shanghai 13 trial was a randomised, open-label, multicentre, phase 2 trial. Patients (aged ≥18 years) were recruited from six hospitals in China with histological confirmation of oligometastatic oesophageal squamous cell carcinoma with a controlled primary tumour and one to four metastatic lesions. Eligible patients were randomly assigned via a computer-generated schedule in a 1:1 ratio to receive either systemic therapy alone (ie, systemic therapy only group) or combined systemic and local therapy (ie, systemic and local therapy group). The systemic therapy regimens in both groups were at the discretion of the investigator and included chemotherapy alone, anti-PD-1 antibodies alone, or chemotherapy plus anti-PD-1 antibodies. Local therapy-radiotherapy, surgery, or thermal ablation-was delivered to all metastatic lesions for patients in the systemic and local therapy group. Randomisation was balanced dynamically on three factors: the number of disease sites, the lines of systemic therapy, and the location of the metastases. Patients and investigators were not masked to treatment allocation. The primary endpoint was progression-free survival, defined as the time from randomisation to progression or death from any cause in the intention-to-treat population. The safety population included all patients who had undergone random assignment and at least one of the intended therapies. This trial is registered with ClinicalTrials.gov, NCT03904927. The trial is ongoing but closed to new participants. FINDINGS: 116 patients were screened for enrolment between March 5, 2019, and Sept 16, 2021, and 104 patients who met the eligibility criteria were randomly assigned to the systemic and local therapy group (n=53) or the systemic therapy only group (n=51). 20 (38%) patients in the systemic plus local therapy group and 23 (45%) patients in the systemic therapy only group received anti-PD-1 antibody-based systemic therapy; three patients in the systemic and local therapy group did not receive systemic therapy. At a median follow-up of 30·5 months (IQR 24·7-37·8), median progression-free survival was 15·3 months (95% CI 10·1-20·5) in the systemic and local therapy group versus 6·4 months (5·2-7·6) in the systemic therapy only group (stratified hazard ratio 0·26 [95% CI 0·16-0·42]; stratified log rank p<0·0001). Grade 1-2 acute oesophagitis was more common in the systemic and local therapy group than in the systemic therapy only group (10 [19%] vs one [2%] patients; p=0·036). The number of patients who had grade 3 or worse treatment-related adverse events was similar between groups (25 [47%] vs 21 [41%]; p=0·538), with the most common adverse events being leukocytopenia (17 [32%] vs 18 [35%]) and neutropenia (19 [36%] vs 20 [39%]). Treatment-related deaths occurred in two patients in the systemic and local therapy group and one patient in the systemic therapy only group. INTERPRETATION: The addition of local treatment for metastases could significantly improve progression-free survival among patients with oligometastatic oesophageal squamous cell carcinoma being treated with systemic therapy. Our findings suggest that combining local and systemic therapy could be a treatment option for patients with oligometastatic oesophageal squamous cell carcinoma, but further support from phase 3 trials is required. FUNDING: Science and Technology Commission of Shanghai Municipality, National Nature Science Foundation of China, and Shanghai Municipal Health Commission. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Lymphocyte recovery from radiation-induced lymphopenia in locally advanced esophageal squamous cell carcinoma: correlations with prognosis and lymphocyte-related organs.

BACKGROUND: Limited studies explored the relationship between lymphocyte recovery after definitive concurrent chemoradiotherapy (dCCRT) and prognosis in esophageal squamous cell carcinoma (ESCC). METHODS: ESCC patients with obtainable absolute lymphocyte counts (ALCs) at 6 months after dCCRT were screened from prospective trials. Patients were divided into groups according to the grade of ALC nadir during radiotherapy (G4 or G1-3) and lymphocyte recovery status, which was assessed by lymphocyte recovery index (LRI), calculated as the ratio of post- to pre-treatment lymphocyte counts. Cox analysis was conducted to evaluate the prognostic significance of lymphocyte recovery status. Irradiated relative volumes of the bone marrow (BM) and spleen and effective dose to immune cells (EDIC) were collected to identify their impacts on lymphocyte recovery status by logistic analysis. RESULTS: 232 patients were enrolled. In 69 patients with G4 ALC nadir (group A and B) and 163 patients with G1-3 ALC nadir (group C and D) during dCCRT, 27 (group A) and 67 (group C) patients showed an insufficient level of lymphocyte recovery (LRI < 60%), and 42 (group B) and 96 (group D) patients showed a satisfactory level of lymphocyte recovery (LRI ≥ 60%). Cox multivariable analysis revealed that inadequate lymphocyte recovery was significantly associated with worse overall survival (HR, 2.80 and 1.70) and local recurrence-free survival (HR, 2.82 and 1.60) both in group A vs group B and group C vs group D. Logistic analysis identified BM V5 (OR 4.24 and 2.29) as an independent predictor of inadequate lymphocyte recovery from G4 or G1-3 ALC nadir, respectively. CONCLUSIONS: Insufficient lymphocyte recovery might serve as a valuable prognostic factor, regardless of whether patients experienced G4 or G1-3 ALC nadir during radiotherapy. Additionally, it was observed that a larger relative volume of BM receiving ≥ 5 Gy was correlated with a higher risk of insufficient lymphocyte recovery.

Radiotherapy for Advanced Esophageal Cancer: from Palliation to Curation.

OPINION STATEMENT: Esophageal cancer is a global health problem, which is 7th most common and 6th most deadly cancer. It has been the era of immuno-oncology for esophageal cancer management. Radiation therapy has been one of the key local therapeutic approaches for esophageal cancer treatment, while its role in advanced disease is challenging and debatable. There have been emerging clinical and translational studies of radiation therapy in recurrent or metastatic esophageal cancer. Immunotherapy has been established the standard care of 1st and 2nd line systemic therapies of advanced esophageal cancer, and the development of tumor immunity has opened a new chapter for the esophageal cancer radiation therapy. The current review will summarize the classic radiation therapy research in advanced esophageal cancer, as well as the most recent key findings. The subtitles will cover palliative radiotherapy for dysphagia, re-radiation for recurrent disease, oligo-focal disease management and stereotactic radiation therapy, and radiotherapy with immunotherapy. Radiotherapy plays vital role in multidisciplinary management of advanced EC. External or intratumoral irradiation has been used for palliation of dysphagia and improving QOL in esophageal cancer patients traditionally, while recent clinical and technical advance enables radiotherapy to be considered in recurrent or metastatic disease for curation attention. Novel clinical and translational investigation is opening a new chapter of radiotherapy with immunotherapy for benefiting advanced EC patients.

Interim position emission tomography-computed tomography during multimodality treatment of locally advanced esophageal cancer: a scoping review.

Background: Among cancers, esophageal cancer (EC) has one of the highest incidences and mortality in Asia. As recognized in many national guidelines, functional imaging performed with position emission tomography is recommended for patients with locally advanced disease. This review evaluated evidence for the use of fluorodeoxyglucose (FDG) interim positron emission tomography (PETint) in bimodality (chemoradiation) and trimodality (chemoradiation followed by surgery) management of locally advanced esophageal cancer (LAEC), with a focus on its prognostic and predictive value. Methods: The MEDLINE database was searched from January 1, 2001, to January 1, 2022, as part of a scoping review. References of selected articles were manually checked to identify other articles meeting the inclusion criteria; only original articles were included, and reviews, guidelines, letters, editorials, and case reports were excluded. Results: A total of 63 articles were included in this review. PET-computed tomography (PET-CT) is recognized as having a significant role in the assessment of treatment response. Studies on the predictive PETint suggest that it has a certain value, particularly for early response. Identification of poor responders or nonresponders soon after commencement of multimodality treatment allows for treatment modification. Conclusions: The scoping review indicated variable utility for the prognostic value of PETint. There is a need to improve its accuracy, which can likely be achieved through greater standardization of measurements and reporting and testing as well as combination with other promising measures of response to residual disease.

Mutant HTT does not affect glial development but impairs myelination in the early disease stage.

Introduction: Huntington's disease (HD) is caused by expanded CAG repeats in the huntingtin gene (HTT) and is characterized by late-onset neurodegeneration that primarily affects the striatum. Several studies have shown that mutant HTT can also affect neuronal development, contributing to the late-onset neurodegeneration. However, it is currently unclear whether mutant HTT impairs the development of glial cells, which is important for understanding whether mutant HTT affects glial cells during early brain development. Methods: Using HD knock-in mice that express full-length mutant HTT with a 140 glutamine repeat at the endogenous level, we analyzed the numbers of astrocytes and oligodendrocytes from postnatal day 1 to 3 months of age via Western blotting and immunocytochemistry. We also performed electron microscopy, RNAseq analysis, and quantitative RT-PCR. Results: The numbers of astrocytes and oligodendrocytes were not significantly altered in postnatal HD KI mice compared to wild type (WT) mice. Consistently, glial protein expression levels were not significantly different between HD KI and WT mice. However, at 3 months of age, myelin protein expression was reduced in HD KI mice, as evidenced by Western blotting and immunocytochemical results. Electron microscopy revealed a slight but significant reduction in myelin thickness of axons in the HD KI mouse brain at 3 months of age. RNAseq analysis did not show significant reductions in myelin-related genes in postnatal HD KI mice. Conclusion: These data suggest that cytoplasmic mutant HTT, rather than nuclear mutant HTT, mediates myelination defects in the early stages of the disease without impacting the differentiation and maturation of glial cells.

Less Irradiation to Lymphocyte-Related Organs Reduced the Risk of G4 Lymphopenia in Esophageal Cancer: Re-Analysis of Prospective Trials.

BACKGROUND: This study aimed to explore the relationship between irradiation of lymphocyte-related organs at risk (LOARs) and lymphopenia during definitive concurrent chemoradiotherapy (dCCRT) for esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Cases of ESCC patients who received dCCRT from 2 prospective clinical trials were identified. To find its correlation with survival outcomes, grades of absolute lymphocyte counts (ALCs) nadir during radiotherapy were recorded following COX analysis. Associations of lymphocytes at nadir and dosimetric parameters including relative volumes of spleen and bone marrow receiving 0.5, 1, 2, 3, 5, 10, 20, 30, and 50Gy (V0.5, V1, V2, V3, V5, V10, V20, V30, and V50), and effective dose to circulating immune cells (EDIC) were examined by logistic risk regression analysis. The cutoffs of dosimetric parameters were determined by the receiver operating characteristic curve (ROC). RESULTS: A total of 556 patients were included. The incidences of grades 0, 1, 2, 3, and 4 (G4) lymphopenia during dCCRT were 0.2%, 0.5%, 9.7%, 59.7%, and 29.8%, respectively. Their median overall survival (OS) and progression-free survival (PFS) time were 50.2 and 24.3 months, respectively; the incidence of local recurrence and distant metastasis were 36.6% and 31.8%, respectively. Patients once suffering from G4 nadir during radiotherapy had unfavorable OS (HR, 1.28; P = .044) and a higher incidence of distant metastasis (HR, 1.52; P = .013). Furthermore, patients with EDIC ≤8.3Gy plus spleen V0.5 ≤11.1% and bone marrow V10 ≤33.2% were strongly associated with lower risk of G4 nadir (OR, 0.41; P = .004), better OS (HR, 0.71; P = .011) and lower risk of distant metastasis (HR, 0.56; P = .002). CONCLUSIONS: Smaller relative volumes of spleen V0.5 and bone marrow V10 plus lower EDIC were jointly prone to reduce the incidence of G4 nadir during definitive concurrent chemoradiotherapy. This modified therapeutic strategy could be a significant prognostic factor for survival outcomes in ESCC.

Immune characteristics and genetic markers of esophageal cancer by single-cell analysis: implications for immunotherapy.

Background: Esophageal cancer (EC) is one of the most common cancers worldwide. The prognoses for patients with the same stage of EC can vary substantially. The progress of single-cell analysis technology has furthered the understanding of tumor heterogeneity. This paper aimed to apply single-cell analysis to explore the characteristics of the tumor environment of EC and provide a basis for personalized treatment. Methods: The latest gene expression data and clinical follow-up information of single-cell sequencing results of EC samples were downloaded from The Cancer Genome Atlas (TCGA) Genomic Data Commons (GDC) Application Programming Interface (API). A differential gene function analysis of the immune infiltration signature agents in the tumor microenvironment (TME) was performed using bioinformatics analytical methods, and potential molecular targets were sought. Results: We identified specific cell subsets in the EC and paracancerous samples, including panel cells, natural killer (NK) cells, exhausted cluster of differentiation (CD)8+ T cells, CD8+ memory T (Tcm) cells, and effector memory T (Tem) cells, including B cell enrichment in the cancer samples. Differences were detected between B cells and monocytes in stage II and III tumors, which may be related to RNA transcription and degradation. The CXCL8 protein was identified as a valid potential prognostic marker. Conclusions: Cell groups with homogenous cell surface markers exhibit intercellular variations that exert a considerable effect on cell function. Our study will contribute to the understanding of the TME and cellular heterogeneity in EC patients and serve as a valuable resource for in-depth exploration of the pathogenesis of EC and the identification of potential therapeutic targets in the future.

Epidemiological landscape of esophageal cancer in Asia: Results from GLOBOCAN 2020.

BACKGROUND: Esophageal cancer (EC) is a global health problem. Asia represents a huge burden of EC globally, and incidence and mortality vary considerably across different Asian regions. METHODS: Data on incidence, mortality, and preference were extracted from GLOBOCAN 2020. Age-standardized incidence and mortality rates were calculated overall by sex, age, country, region, and continent. The predicted burden of incidence and mortality in 2040 was calculated based on global demographic projections. RESULTS: It was estimated there were 481 552 new cases of and 434 363 deaths from EC in Asia in 2020, accounting for 79.7% and 79.8% of world EC cases and deaths, respectively. EC incidence and mortality in Asia ranked the highest among all continents. Eastern Asia represents the highest age-standardized world incidence rate (ASWIR) of 12.3 per 100 000 for all Asian regions. Western Asia represents the lowest ASWIR of 1.7 per 100 000, accounting for 0.7% of the globe. There exist obvious differences in epidemiological features in Asian countries, including incidence, mortality, prevalence, and mortality incidence ratio. There is forecast to be up to 781 000 new cases of EC in Asia by 2040, with increasing rates of 63% for incidence and 72% for mortality from 2020. CONCLUSIONS: Asia has an increasing number of EC cases and deaths. Strategies for targeting in high-incidence areas, the elderly, and survival should be prioritized to reduce the global EC burden, especially in low- and middle-income countries in Asia.

Comparison of treatment strategies for resectable locally advanced primary mucinous adenocarcinoma of the lung.

BACKGROUND: Primary pure mucinous adenocarcinoma (PMA) is a rare type of lung cancer with unique clinical and prognostic features. Previous studies have shown that PMA have more early-stage cancer compared with other adenocarcinoma (ADC) subtypes. The clinicopathological features and optimal treatment strategies of resectable locally advanced mucinous adenocarcinoma lack evidence and require further study. METHODS: In this study, we collected information from patients with stage III-N2 PMA who underwent radical surgery between 2004 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) database. The clinicopathological parameters, treatments, overall survival (OS), and cancer-specific survival (CSS) were evaluated. RESULTS: Of 242,699 eligible lung adenocarcinoma patients, 124 with PMA and 3405 with other ADCs of stage III-N2 received radical surgery were identified. Compared with other ADCs, PMA tended to appear more in the lower lobes, with higher degree of differentiation, less early T stage, and more positive lymph nodes numbers. Patients with PMA had significantly worse survival than other ADCs (OS = 45.0 vs. 57.1 months, p = 0.005, CSS = 51.8 vs. 65.5 months, p = 0.017). We explored the benefit population of postoperative radiotherapy (PORT) and found that the population with ≤7 positive lymph nodes could benefit from PORT, and OS was significantly improved (41.2 vs. 69.3 months, p = 0.034). For patients with >7 positive lymph nodes, PORT did not provide a survival benefit, while chemotherapy improved OS (10.9 vs. 23.3 months, p = 0.041). Multivariate analysis showed that race, tumor location, number of positive lymph nodes, and PORT were independent prognostic factors in patients with postoperative III-N2 lung PMA. CONCLUSION: The prognosis of patients with resectable III-N2 primary lung PMA was significantly worse than that of other ADCs, and PORT was an independent prognostic factor. Patients with ≤7 positive lymph nodes could benefit from PORT and those with >7 positive lymph nodes could benefit from chemotherapy.

Career and Professional Development for Young Oncologists.

Young oncologists around the globe face many challenges when it comes to their career and professional development. Aspects such as time management, work-life balance, career progression, and educational opportunities are only some of them. Professional societies have identified these challenges in this professional group and designed programs to tackle them specifically. The importance of this strategy cannot be overstated, as young oncologists, defined by most societies as oncologists under 40 years of age, compose almost 50% of the oncology workforce. On the other hand, recent surveys have shown that many young oncologists are considering alternative career paths due to burnout issues aggravated by the COVID-19 pandemic, on top of all other challenges. The virtual setting that has been forcedly introduced into our professional life has shortened distances between professionals and might have contributed to more accessible access to information and opportunities that some young oncologists could not profit from due to their traveling constraints. On the other hand, this virtual setting has shown us the asymmetries in opportunities for these professionals. Knowledgeable of all this, we summarize in this article some of the career and professional development offers available to all young oncologists, which we consider could help them deal with current and future challenges.

Esophageal cancer in China: Practice and research in the new era.

China, as the one of the largest developing countries in the world and with about one-fifth of the global population, is bearing an increasing burden on health from cancer. In the area of esophageal cancer (EC), China accounts for more than 50% of the global cases, with this disease being a particularly worse for those in disadvantaged populations. Along with China's socioeconomic condition, the epidemiology, diagnosis, therapeutics and research of EC have developed throughout the 21st century. In the current review, existing control measures for EC in China are outlined, including the incidence, mortality, screening, clinical diagnosis, multidisciplinary treatment and research landscape. EC in China are very different from those in some other parts of the world, especially in Western countries. Core measures that could contribute to the prevention of EC and improve clinical outcomes in patients of less developed countries and beyond are recommended. International cooperation among academia, government and industry is especially warranted in global EC control.

Axillary management in patients with clinical node-negative early breast cancer and positive sentinel lymph node: a systematic review and meta-analysis.

Background: The omission of axillary lymph node dissection (ALND) or axillary radiation (AxRT) remains controversial in patients with clinical node-negative early breast cancer and a positive sentinel lymph node. Methods: We conducted a comprehensive review by searching PubMed, Embase, Web of Science, and Cochrane databases (up to November 2023). Our primary outcomes were overall survival (OS), disease-free survival (DFS), locoregional recurrence (LRR), and axillary recurrence (AR). Results: We included 26 studies encompassing 145,548 women with clinical node-negative early breast cancer and positive sentinel lymph node. Pooled data revealed no significant differences between ALND and sentinel lymph node biopsy (SLNB) alone in terms of OS (hazard ratio [HR]0.99, 95% confidence interval [CI] 0.91-1.08, p=0.84), DFS (HR 1.04, 95% CI 0.90-1.19, p=0.61), LRR (HR 0.76, 95% CI 0.45-1.20, p=0.31), and AR (HR 1.01, 95% CI 0.99-1.03, p=0.35). Similarly, no significant differences were observed between AxRT and SLNB alone for OS (HR 0.57, 95% CI 0.32-1.02, p=0.06) and DFS (HR 0.52, 95% CI 0.26-1.05, p=0.07). When comparing AxRT and ALND, a trend towards higher OS was observed the AxRT group (HR 0.08, 95% CI 0.67-1.15), but the difference did not reach statistical significance (p=0.35, I2 = 0%). Additionally, no significant differences significance observed for DFS or AR (p=0.13 and p=0.73, respectively) between the AxRT and ALND groups. Conclusion: Our findings suggest that survival and recurrence rates are not inferior in patients with clinical node-negative early breast cancer and a positive sentinel lymph node who receive SLNB alone compared to those undergoing ALND or AxRT.

CBX4 contributes to radioresistance by regulating autophagic activity in esophageal squamous cell carcinoma.

Background: The function of Chromobox 4 (CBX4) function has attracted attention in many cancer types due to its unique biological role; however, its mechanism in esophageal squamous cell carcinoma (ESCC) under radiotherapeutic treatment has not yet been investigated. Methods: Silencing of CBX4 was carried out in TE-13 and KYSE-150 cell lines. Cell proliferation, radiosensitivity, DNA damage, apoptosis, and cell cycle distribution were determined by Cell Counting Kit-8 (CCK-8), colony formation assay, immunofluorescence, flow cytometry, and immunoblot in vitro. In vivo xenograft models were also used to assess tumor cell growth and radioresistance. The underpinning mechanisms were explored based on pathway analysis and confirmed by rescue experiments, detecting cellular autophagy. Results: Knockdown of CBX4 resulted in reduced tumor growth and enhanced radio-response in vivo and in vitro. Down-regulating CBX4 increased DNA damage, apoptotic rate, and G2/M arrest induced by radiation in ESCC cell lines. Gene Set Enrichment Analysis (GSEA) revealed that CBX4 was associated with cellular autophagy regulation. Enhanced radiosensitivity in ESCC cells silenced for CBX4 was partially blocked by autophagy inhibition (P<0.05). Beclin 1 was upregulated at the gene and protein levels in ESCC cells with CBX4 knockdown after irradiation, and overexpressing Beclin 1 reversed the radiosensitivity of ESCC cells with CBX4 knockdown (P<0.05). Conclusions: By regulating autophagic activity, CBX4 contributes to radioresistance. Targeting CBX4 might constitute an efficient approach for increasing radiosensitivity in ESCC.

Downregulation of LEMD1-AS1 and Its Influences on the Diagnosis, Prognosis, and Immune Infiltrates of Epithelial Ovarian Cancer.

Previous studies have confirmed long noncoding RNA LEMD1-AS1 (LEMD1-AS1) as a functional factor in several tumors. The present work is aimed at exploring the prognostic and diagnostic values of LEMD1-AS1 in patients with epithelial ovarian cancer (EOC). We examined the expressions of LEMD1-AS1 in pan-cancer from TCGA microarray datasets and GTEx Project. The expressions of LEMD1-AS1 were detected by qRT-PCR in EOC specimens and normal ovarian specimens from 30 EOC patients. The χ 2 test was applied to compare the clinicopathological characteristics of different groups. ROC curves were established to determine the diagnostic values of LEMD1-AS1 in screening EOC tissues. The association of LEMD1-AS1 expression with clinical outcome was determined by the Kaplan-Meier methods and COX assays. A decreased expression of LEMD1-AS1 was observed in EOC tissues compared to matched normal specimens (p < 0.01). Low LEMD1-AS1 expression could be used to distinguish EOC from adjacent normal specimens. A clinical study revealed that patients with low LEMD1-AS1 expression have a shorter overall survival (p = 0.035) and progress-free interval (p = 0.041) than those with high LEMD1-AS1 expression. The Spearman correlation test revealed that LEMD1-AS1 expressions were negatively associated with the expressions of neutrophil and myeloid dendritic cell. Overall, our finding suggested that LEMD1-AS1 may have potential roles as a potential biomarker and/or a therapeutic target in EOC.

PD-1 Inhibitor Enhanced Radiosensitivity by Reactivating T Cells and Inducing G2/M Phase Arrest in Esophageal Squamous Cell Carcinoma.

Radiotherapy is a main treatment for esophageal squamous cell carcinoma (ESCC), but radioresistance leads to treatment failure ultimately. The combination of radiotherapy and PD-1 inhibitors showed significant antitumor effects. Our study showed that high-immune score, IFNG and CD8A level were associated with a low-radiosensitivity index (RSI) in the TCGA-ESCC cohort. And blocking PD-1 promoted exhausted T cells proliferation and IFN-γ expression. PD-1 inhibitor-reactivated T cells promoted G2/M-phase arrest, apoptosis and impaired DNA damage in radioresistant cells in an IFN-γ-dependent manner. Our study showed PD-1 inhibitors promote radiosensitivity though enhancing exhausted T cells expansion and IFN-γ expression, and highlights that neoadjuvant anti-PD-1 therapy and radiotherapy could offer an optimum strategy for improving cancer patients' outcome.

Dose escalation based on 18F-FDG PET/CT response in definitive chemoradiotherapy of locally advanced esophageal squamous cell carcinoma: a phase III, open-label, randomized, controlled trial (ESO-Shanghai 12).

INTRODUCTION: Definitive chemoradiotherapy has established the standard non-surgical treatment for locally advanced esophageal cancer. The standard dose of 50-50.4 Gy has been established decades ago and been confirmed in modern trials. The theorical advantage of better local control and technical advances for less toxicity have encouraged clinicians for dose escalation investigation. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) have the potential to tailor therapy for esophageal patients not showing response to CRT and pioneers the PET-based dose escalation. METHODS AND ANALYSIS: The ESO-Shanghai 12 trial is a prospective multicenter randomized phase 3 study in which patients are randomized to either 61.2 Gy or 50.4 Gy of radiation dose by PET response. Both groups undergo concurrent chemoradiotherapy with paclitaxel/cisplatin regimen for 2 cycles followed by consolidation chemotherapy for 2 cycles. Patients with histologically confirmed ESCC [T1N1-3M0, T2-4NxM0, TxNxM1 (Supraclavicular lymph node metastasis only), (AJCC Cancer Staging Manual, 8th Edition)] and without any prior treatment of chemotherapy, radiotherapy or surgery against esophageal cancer will be eligible. The primary endpoints included overall survival in PET/CT non-responders (SUVmax > 4.0) and overall survival in total population. Patients will be stratified by standardized uptake volume, gross tumor volume and tumor location. The enrollment could be ended, when the number of PET/CT non-responder reached 132 and the total population reached 646 for randomization. ETHICS AND DISSEMINATION: This trial has been approved by the Fudan University Shanghai Cancer Center Institutional Review Board. Trial results will be disseminated via peer reviewed scientific journals and conference presentations. Trial registration The trial was initiated in 2018 and is currently recruiting patients. Trial registration number NCT03790553.

Effects of internet-based cognitive behavioral therapy on postpartum depression: A protocol for systematic review and meta-analysis.

BACKGROUND: Postpartum depression is one of the most common complications during the postpartum period. In recent years, internet-based psychological interventions have made significant progress and provided a new psychotherapy model. Internet-based cognitive behavioral therapy (ICBT) for postpartum depression has achieved good results. However, the effectiveness of ICBT for postpartum depression reported by different studies still remains inconsistent. Therefore, a meta-analysis was used to further evaluate the efficacy of ICBT for postpartum depression, aiming to provide evidence to support nonpharmacological intervention strategies in the clinic. METHODS: The databases of PubMed, Web of Science, Scopus, Cochrane Library, Embase, China Scientific Journal Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wanfang Data will be searched. The randomized controlled trials of ICBT will be included for postpartum depression published before February 2022. Two independent researchers will independently complete literature selection, risk of bias assessment and data extraction. The disagreements will be discussed with a third party for the final decision. Cochrane Risk of Bias Assessment Tool will be used for literature quality assessment. Data processing will be conducted by RevMan 5.4 software. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSIONS: For the question whether ICBT for postpartum depression is efficacy, this study can provide more comprehensive and strong evidence. ETHICS AND DISSEMINATION: The ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/EQJDH.

The effectiveness of mindfulness-based stress reduction intervention on alleviating anxiety and depression in postoperative patients with cervical cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: Surgical treatment for cervical cancer, as a stressor, largely leads to strong psychological reactions to stress like anxiety and depression. Whether mindfulness-based stress reduction (MBSR) can alleviate anxiety and depression in patients after cervical cancer surgery is controversial. Therefore, we aim to perform a meta-analysis involving randomized controlled trials analyzing the effect of MBSR on alleviating anxiety and depression in patients after cervical cancer surgery, thus providing evidence-based medical evidences for nonpharmacological interventions. METHODS: Randomized controlled trials analyzing the effect of MBSR on alleviating anxiety and depression in patients after cervical cancer surgery will be searched in online databases, including Cochrane Central Register of Controlled Trials Repositories, PubMed, Embase, Web of Science, Chinese Science Citation Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, and Wan Fang Data. After screening eligible studies, we will perform a meta-analysis on the effect of MBSR on alleviating anxiety and depression in patients after cervical cancer surgery. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will provide reliable evidence-based evidences for the effects of MBSR on alleviating anxiety and depression in patients after cervical cancer surgery. ETHICS AND DISSEMINATION: Ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/EXUM3.