Predictive Value of Jugulo-omohyoid Lymph Nodes in Lateral Lymph Node Metastasis of Papillary Thyroid Cancer.

BACKGROUND: Jugulo-omohyoid lymph nodes (JOHLN) metastasis has proven to be associated with lateral lymph node metastasis (LLNM). This study aimed to reveal the clinical features and evaluate the predictive value of JOHLN in PTC to guide the extent of surgery. METHODS: A total of 550 patients pathologically diagnosed with PTC between October 2015 and January 2020, all of whom underwent thyroidectomy and lateral lymph node dissection, were included in this study. RESULTS: Thyroiditis, tumor location, tumor size, extra-thyroidal extension, extra-nodal extension, central lymph node metastasis (CLNM), and LLMM were associated with JOHLN. Male, upper lobe tumor, multifocality, extra-nodal extension, CLNM, and JOHLN metastasis were independent risk factors from LLNM. A nomogram based on predictors performed well. Nerve invasion contributed the most to the prediction model, followed by JOHLN metastasis. The area under the curve (AUC) was 0.855, and the p-value of the Hosmer-Lemeshow goodness of fit test was 0.18. Decision curve analysis showed that the nomogram was clinically helpful. CONCLUSION: JOLHN metastasis could be a clinically sensitive predictor of further LLM. A high-performance nomogram was established, which can provide an individual risk assessment of LNM and guide treatment decisions for patients.

Distinct risk factors of lateral lymph node metastasis in patients with papillary thyroid cancer based on age stratification.

INTRODUCTION: Studies have revealed that age is associated with the risk of lateral lymph node metastasis (LLNM) in papillary thyroid cancer (PTC). This study aimed to identify the optimal cut point of age for a more precise prediction model of LLNM and to reveal differences in risk factors between patients of distinct age stages. METHODS: A total of 499 patients who had undergone thyroidectomy and lateral neck dissection (LND) for PTC were enrolled. The locally weighted scatterplot smoothing (LOWESS) curve and the 'changepoint' package were used to identify the optimal age cut point using R. Multivariate logistic regression analysis was performed to identify independent risk factors of LLNM in each group divided by age. RESULTS: Younger patients were more likely to have LLNM, and the optimal cut points of age to stratify the risk of LLNM were 30 and 45 years old. Central lymph node metastasis (CLNM) was a prominent risk factor for further LNM in all patients. Apart from CLNM, sex(p = 0.033), tumor size(p = 0.027), and tumor location(p = 0.020) were independent predictors for patients younger than 30 years old; tumor location(p = 0.013), extra-thyroidal extension(p < 0.001), and extra-nodal extension(p = 0.042) were independent risk factors for patients older than 45 years old. CONCLUSIONS: Our study could be interpreted as an implication for a change in surgical management. LND should be more actively performed when CLNM is confirmed; for younger patients with tumors in the upper lobe and older patients with extra-thyroidal extension tumors, more aggressive detection of the lateral neck might be considered.

The minimal number of examined lymph nodes for accurate nodal staging and favorable prognosis in T1-2 supraglottic laryngeal squamous cell carcinoma.

OBJECTIVE: The study aimed to investigate the minimal number of examined lymph nodes (ELNs) for accurate assessment of lymph node status and favorable prognosis in patients with stage T1-2 supraglottic laryngeal squamous cell carcinoma (LSCC) who received radical resection. METHODS: Patients with stage T1-2 supraglottic LSCC from the Surveillance, Epidemiology, and End Results (SEER) database and the Chinese Academy of Medical Sciences, Cancer Hospital/National Cancer Center (NCC) were reviewed. The association of the ELN count with the identification of nodal metastasis and overall survival (OS) was analyzed using a multivariate regression model. Locally weighted scatterplot smoothing fitting curve and the 'changepoint' package were adopted to identify the optimal cut points using R. RESULTS: A total of 429 patients from the SEER database and 53 patients from NCC were enrolled. The probability of identifying nodal metastasis was positively related to the ELN count. For patients diagnosed with pathological stage N0 (pN0) disease, the mortality risks rapidly decreased when the amount of ELNs exceeded ten, and those with ELNs >10 had better OS. CONCLUSION: An adequate amount of ELNs benefits precise nodal staging in patients with stage T1-2 supraglottic LSCC. Ten lymph nodes are the minimum number of ELNs. For pN0 patients, an ELN count ≤10 is an unfavorable prognostic factor.

The Optimal Age Threshold for Stratifying the Risks of Disease Progression in Patients with Highly Suspicious Sub-centimeter Thyroid Nodules.

PURPOSE: The study aimed to identify the value and optimal age cutoff to predict the progression of highly suspicious thyroid nodules ≤ 10 mm during active surveillance (AS), and to reveal distinct risk factors in patients of different ages. METHODS: A total of 779 patients with highly suspicious thyroid nodules were enrolled and followed up by ultrasonography. Locally weighted scatterplot smoothing (LOWESS) and the package 'changepoint' were used to identify the optimal age cutoffs using R. Multivariate Cox regression was performed to identify independent prognostic factors in each patient group divided according to age. RESULTS: Age was an independent predictor of nodule progression (P = 0.038). The optimal age cutoff to stratify the risk of nodule progression was 30 years. Younger patients were more likely to have progression of nodules during AS (P < 0.001), including enlargement of nodule size (P = 0.011) and new lesion occurrence (P < 0.001). Nodule size was identified as a risk factor for disease progression in patients younger than 30 years old (P = 0.008, OR 7.946, 95% CI 1.715-36.820), while multifocality (P = 0.018, OR 2.315, 95% CI 1.155-4.639) and thyroiditis (P = 0.028, OR 2.265, 95% CI 1.092-4.699) were independent predictors in patients over 30 years old. CONCLUSIONS: Highly suspicious thyroid nodules ≤ 10 mm in young patients tended to be more progressive. The predictors of disease progression were distinct in patients of different ages.

The optimal number of examined lymph nodes for accurate nodal staging and favorable prognosis of oral tongue squamous cell carcinoma.

OBJECTIVE: The study aimed to determine the optimal count of examined lymph nodes (ELN) for accurate assessment of lymph node status and favorable long-term survival in patients with oral tongue squamous cell carcinoma (OTSCC) who received radical resection. METHODS: Patients with OTSCC who received radical resection between 2004 and 2015 were enrolled from the Surveillance, Epidemiology, and End Results database (SEER) and were randomly divided into two cohorts. The association of ELN count with nodal migration and overall survival (OS) was analyzed using a multivariate regression model with the adjustment of relevant factors. Locally weighted scatterplot smoothing (LOWESS) and 'strucchange' package were adopted to identify the optimal cut points using R. RESULTS: A total of 2077 patients were included in this study. The optimal cut points of ELN count for accurate nodal staging and favorable OS were 19 and 15, respectively. The probability of detecting positive lymph nodes (PLN) significantly increased in patients with ELN count ≥ 19 in comparison to those with ELN count < 19 (training set, P < 0.001; validation set, P = 0.012). A better postoperative prognosis was observed in patients with ELN count ≥ 15 than those with fewer ELN (training set, P = 0.001, OR: 0.765; validation set, P = 0.016, OR: 0.678). CONCLUSION: The optimal cut point of ELN count to ensure the accuracy of nodal staging and to achieve a favorable postoperative prognosis were 19 and 15, respectively. The ELN count beyond the cutoff values might improve the accuracy of cancer staging and OS.

Prognostic prediction of lung adenocarcinoma by integrative analysis of RHOH expression and methylation.

BACKGROUND AND OBJECTIVE: The development of epigenetics holds great promise for diagnosis and treatment of lung adenocarcinoma (LUAD). The purpose of this work was to analyze the correlation between Ras Homolog Gene Family Member H (RHOH) expression and methylation in patients with LUAD and its association with survival. METHODS: Data related to gene expression, DNA methylation, and clinical features of LUAD from The Cancer Genome Atlas (TCGA) database were analyzed. A total of 50 patients were included in verification group. The methylation level of RHOH in verification group was detected by bisulfite amplicon sequencing. RESULTS: The RHOH methylation level in TCGA cohort was significantly and negatively correlated with its expression level (Cor = -0.5, p = 2.687e-33). Patients with hypermethylation and low expression of RHOH had significantly worse prognosis than patients with hypomethylation and low expression of RHOH (TCGA: p = 0.004; validation cohort: p = 0.006, HR: 4.740, 95% CI: 1.567-14.340). CONCLUSION: Our research revealed that RHOH may prove to be a new potential prognostic predictor for LUAD patients.

Survival and long-term quality-of-life of concurrent chemoradiotherapy versus surgery followed by radiotherapy with or without concurrent chemotherapy for the treatment of resectable stage III/IV hypopharyngeal carcinoma.

OBJECTIVE: We evaluated the utility of concurrent chemoradiotherapy (CCRT) compared to surgery followed by adjuvant radiotherapy (with or without concurrent chemotherapy) (SRT) in terms of improving the life expectancy and quality-of-life (QOL) of patients with stage III/IV hypopharyngeal squamous cell carcinomas (HPSCCs). METHODS: From January 2010 to July 2018, a total of 299 patients with stage III/IV HPSCC who received surgery followed by adjuvant radiotherapy (with or without concurrent chemotherapy) (SRT, n = 111), or concurrent chemoradiotherapy (CCRT, n = 188) in our hospital were included. We measured overall survival (OS) and disease-free survival (DFS). We used the EORTC QLQ-C30, QLQ-H&N35, and Voice handicap index-30 (VHI-30) instruments to assess the long-term QOL. RESULTS: The OS and DFS afforded by SRT were significantly better than those associated with CCRT (p = 0.039; p = 0.048 respectively), especially for stage N2-N3 patients. CCRT patients experienced better speech outcomes. CONCLUSION: For resectable stage III/IV HPSCC patients, appropriate treatment plans should be selected comprehensively considering survival rate, QOL, patient preference and multidisciplinary treatment.

Evaluation of serum B7-H3 expression, ultrasound and clinical characteristics to predict the risk of cervical lymph node metastases in papillary thyroid carcinoma by nomogram.

BACKGROUND: Improving the preoperative diagnosis of cervical lymph node metastasis (LNM) will help improve the clinical outcomes of papillary thyroid carcinoma (PTC) patients. B7-H3, as an immune checkpoint of the B7 family, is highly expressed in PTC tissues and related to LNM and prognosis. We aimed to explore the clinical values of serum B7-H3 (sB7-H3) in predicting LNM in PTC by a nomogram prediction model. METHODS: From September 2019 to May 2021, a total of 344 PTC patients with primary surgery in our hospital were enrolled in this research. Enzyme-linked Immunosorbent Assay (ELISA) was used to detect sB7-H3 from the peripheral blood of PTC patients and normal controls. We created a nomogram prediction model in combination with sB7-H3 expression, clinical and ultrasound characteristics to predict LNM in the early stage. RESULTS: Gender (p = 0.001), age (p = 0.015), tumor size (p < 0.001), number of tumors (p = 0.021) and sB7-H3 expression (p = 0.003) were independent risk factors for LNM in PTC. All the factors were included in the nomogram. The area under the curve (AUC) was 73.9% (95% CI, 68.12%-79.69%). CONCLUSION: The nomogram is helpful in assessing the risk of LNM in PTC. sB7-H3 has excellent potential in predicting LNM in patients with PTC as an adjunctive ultrasound tool.

Overcoming resistance to PD-1/PD-L1 inhibitors in esophageal cancer.

As the predominant treatment option of the immunotherapy for advanced esophageal cancer (EC), the application of programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors brings new hope to clinical practice. However, a considerable portion of patients do not response to this therapy, meanwhile most patients sensitive to PD-1 or PD-L1 antibody initially will develop resistance to the treatment eventually. To break through the limits of clinical effect, it is of critical importance to make a profound understanding of the mechanisms of so called primary resistance and acquired resistance. Subsequently, exploring potent predictors to identify suitable patients for anti-PD-1/PD-L1 treatment and investigating efficient strategies to overcome drug resistance will be helpful to expend the benefit of immunotherapy. In the present view, we summarized the potential predictive factors for anti-PD-1/PD-L1 immunotherapy in EC, and demonstrated the plausible mechanisms of resistance to PD-1/PD-L1 blockade as well as its feasible solutions.

A novel model based on liquid-liquid phase separation-Related genes correlates immune microenvironment profiles and predicts prognosis of lung squamous cell carcinoma.

OBJECTIVE: The aim of the study was to construct and validate a robust prognostic model based on liquid-liquid phase separation (LLPS)-related genes in lung squamous cell carcinoma (LUSC). METHODS: The Cancer Genome Atlas dataset was used as the discovery set to identify the LLPS-related differentially expressed genes (DEGs) between LUSC and normal tissue. These DEGs were screened by the LASSO Cox regression analysis to identify the genes with nonzero coefficient, which were next included in the multivariate Cox regression analysis to construct the prediction model. The dataset GSE41271 was adopted as the validation set to verify the efficacy of the model. Enrichment analysis and the CIBERSORT were performed to illustrate potential immune mechanisms underlying the prediction model. RESULTS: A total of 48 LLPS-related genes were aberrantly expressed in LUSC. Among them, 7 genes were selected by the LASSO Cox regression analysis to construct the prediction model. Risk index (RI) was calculated according to the model for each patient. The prognosis was significantly different between the patients with high and low RI in the discovery set and the validation set (p < 0.001 and p = 0.028, respectively). The multivariate survival analysis confirmed RI as an independent prognostic factor in LUSC (in the discovery set: p < 0.001, HR = 2.643, 95% CI = 1.986-3.518; in the validation set: p = 0.042, HR = 2.144, 95% CI = 1.026-4.480). A series of pathways involving immune cells were found to be related to RI. The distribution pattern of immune cells and chemokines varied according to the value of RI. CONCLUSION: The prediction model based on LLPS-related genes was constructed and validated as a robust prognostic tool for LUSC using multiple datasets. LLPS might have an impact on LUSC through immune pathways.

Impact of post-operative serum albumin level on anastomotic leakage after transthoracic oesophagectomy for oesophageal squamous cell carcinoma.

BACKGROUND: The correlation of post-operative serum albumin level with the occurrence of anastomotic leakage (AL) in oesophageal squamous cell carcinoma (ESCC) remains unclear. The aim of this study was to evaluate the impact of post-operative serum albumin level on AL after transthoracic oesophagectomy. METHODS: Patients with ESCC who underwent transthoracic oesophagectomy between 2013 and 2017 in Fudan University Shanghai Cancer Center were included. The correlation of post-operative serum albumin level with the occurrence and short-term outcomes of AL was analysed. RESULTS: Patients with serum albumin level of <35 g/L on the first post-operative day were identified with higher frequency of AL in the whole study population (10.3% versus 6.1%; P < 0.001), intrathoracic anastomosis subgroup (7.1% versus 3.9%; P = 0.002) and cervical anastomosis subgroup (24.1% versus 16.0%; P = 0.042). Multivariate analysis showed that low albumin level was an independent risk factor of AL in the overall population (odds ratio (OR) 1.842; P < 0.001), intrathoracic anastomosis subgroup (OR 1.815; P = 0.006) and cervical anastomosis subgroup (OR 1.946; P = 0.013). In patients with AL, low albumin level was associated with poorer short-term outcomes. For patients with low albumin level on the first post-operative day, the probability of AL was significantly reduced if the level in the first post-operative week was improved to the normal range (5.9% versus 14.9%; P < 0.001). CONCLUSION: Serum albumin level on the first post-operative day was an independent predictor of AL in patients with ESCC receiving transthoracic oesophagectomy. Increase of albumin level to the normal range post-operatively could reduce the risk of AL.

Immunoscore Signature Predicts Postoperative Survival and Adjuvant Chemotherapeutic Benefits in Esophageal Squamous Cell Carcinoma.

OBJECTIVE: The aim of this study was to construct the immunoscore (IS) to facilitate the prediction of postoperative survival and benefit from adjuvant chemotherapy (ACT) in esophageal squamous cell carcinoma (ESCC). METHODS: A total of 249 patients who received radical esophagectomy at Fudan University Shanghai Cancer Center were divided into training set and testing set. Eighty-nine patients with ESCC from TCGA database were enrolled into the validation set. Myeloid cells in tumor microenvironment were evaluated by immunohistochemistry or CIBERSORT, and then were included into a LASSO Cox regression model to construct the immunoscore. The predictive value of the immunoscore for prognosis after surgery or ACT was analyzed. RESULTS: The immunoscore was constructed by four types of myeloid cells including macrophages, neutrophils, mast cells, and dendritic cells and was demonstrated as IS=2^(0.527719*Mφ -0.2604269*MC-0.4812935*DC-0.4519706*Neu). The overall survival was significantly different between two immunotypes, which were divided according to the immunoscore, in all sets (P<0.001, P=0.005, and P=0.002, respectively). Immunotype A was identified as an independent predictor for survival benefit in all three sets (HR=2.068, P=0.005; HR=2.028, P=0.007; HR=6.474, P=0.007; respectively). In patients who received ACT, immunotype A was significantly related to longer overall survival both in the training set (P<0.001) and in the testing set (P=0.011). The nomogram based on immunotype and other clinicopathological factors showed good efficiency of predicting response to ACT. Finally, several important cytokines and pathways were highly enriched in immunoscore A subgroup. CONCLUSION: The immunoscore was an effective prognostic predictor in ESCC for patients undergoing surgical resection and receiving ACT.

Integrated analysis of optical mapping and whole-genome sequencing reveals intratumoral genetic heterogeneity in metastatic lung squamous cell carcinoma.

BACKGROUND: Intratumoral heterogeneity is a crucial factor to the outcome of patients and resistance to therapies, in which structural variants play an indispensable but undiscovered role. METHODS: We performed an integrated analysis of optical mapping and whole-genome sequencing on a primary tumor (PT) and matched metastases including lymph node metastasis (LNM) and tumor thrombus in the pulmonary vein (TPV). Single nucleotide variants, indels and structural variants were analyzed to reveal intratumoral genetic heterogeneity among tumor cells in different sites. RESULTS: Our results demonstrated there were less nonsynonymous somatic variants shared with PT in LNM than in TPV, while there were more structural variants shared with PT in LNM than in TPV. More private variants and its affected genes associated with tumorigenesis and progression were identified in TPV than in LNM. It should be noticed that optical mapping detected an average of 77.1% (74.5-78.5%) large structural variants (>5,000 bp) not detected by whole-genome sequencing and identified several structural variants private to metastases. CONCLUSIONS: Our study does demonstrate structural variants, especially large structural variants play a crucial role in intratumoral genetic heterogeneity and optical mapping could make up for the deficiency of whole-genome sequencing to identify structural variants.

EGFR-mutant lung adenocarcinoma harboring co-mutational tumor suppressor genes predicts poor prognosis.

INTRODUCTION: EGFR mutations occur most frequently in patients with lung adenocarcinoma in East Asia. However, the prognostic and therapeutic impact of co-mutational status of EGFR and tumor suppressor genes is not fully understood. This study aims to provide a deeper understanding of lung adenocarcinoma patients with co-mutation of EGFR and tumor suppressor genes. METHODS: From November 2009 to May 2016, 675 patients with lung adenocarcinoma who underwent complete surgery were included in this study. Samples were collected and pathologically examined. Whole-exome sequencing was performed on 197 samples, while direct sequencing of major driver genes, including EGFR, KRAS, ERBB2 and BRAF and Ion-torrent targeted sequencing of tumor suppressor genes, including TP53, KEAP1, MGA, NF1, RB1, SMARCA4 and STK11, were performed on 478 samples. Tumor mutational burden was calculated and survival analyses were performed. RESULTS: The frequency of EGFR and TP53 mutation was 409 (60.6%) and 215 (31.9%), respectively. Co-mutation of EGFR and TP53 occured in 151 patients (22.4%), while co-mutation of EGFR and at least one tumor suppressor gene occured in 184 patients (27.3%). Compared with patients with only EGFR mutations, patients with co-mutations of EGFR and TP53 had a higher tumor mutational burden (p = 0.007) and worse recurrence-free survival (p = 0.010), while patients with co-mutations of EGFR and at least one tumor suppressor gene had a higher tumor mutational burden (p = 0.007), worse recurrence-free survival (p = 0.016) and worse overall survival (p = 0.018). CONCLUSIONS: Lung adenocarcinoma patients harboring EGFR and co-mutational tumor suppressor genes should be regarded as a unique subgroup.

FGB and FGG derived from plasma exosomes as potential biomarkers to distinguish benign from malignant pulmonary nodules.

Previous proteomic analysis (label-free) of plasma exosomes revealed that the expression of FGG and FGB was significantly higher in the malignant pulmonary nodules group, compared to the benign pulmonary nodules group. The present study was performed to evaluate the role of plasma exosomal proteins FGB and FGG in the diagnosis of benign and malignant pulmonary nodules. We examined the expression levels of FGB and FGG in plasma exosomes from 63 patients before surgery. Postoperative pathological diagnosis confirmed that 43 cases were malignant and 20 cases were benign. The ROC curve was used to describe the sensitivity, specificity, area under the curve (AUC) of the biomarker and the corresponding 95% confidence interval. We confirmed that the expression levels of FGB and FGG were higher in the plasma exosomes of malignant group than in the benign group. The sensitivity and AUC of FGB combined with FGG detection to determine the nature of pulmonary nodules are superior to single FGB or FGG detection. FGB and FGG might represent novel and sensitive biomarker to distinguish benign from malignant pulmonary nodules.

Proteomic analysis of plasma exosomes to differentiate malignant from benign pulmonary nodules.

BACKGROUND: It is difficult to distinguish benign pulmonary nodules (PNs) from malignant PNs by conventional examination. Therefore, novel biomarkers that can identify the nature of PNs are needed. Exosomes have recently been identified as an attractive alternative approach since tumor-specific molecules can be found in exosomes isolated from biological fluids. METHODS: Plasma exosomes were extracted via the exoEasy reagent method. The major proteins from plasma exosomes in patients with PNs were identified via labelfree analysis and screened for differentially expressed proteins. A GO classification analysis and KEGG pathway analysis were performed on plasma exosomal protein from patients with benign and malignant PNs. RESULTS: Western blot confirmed that protein expression of CD63 and CD9 could be detected in the exosome extract. Via a search of the human Uniprot database, 736 plasma exosome proteins from patients with PNs were detected using high-confidence peptides. There were 33 differentially expressed proteins in the benign and malignant PNs. Of these, 12 proteins were only expressed in the benign PNs group, while 9 proteins were only expressed in the malignant PNs group. We further obtained important information on signaling pathways and nodal proteins related to differential benign and malignant PNs via bioinformatic analysis methods such as GO, KEGG, and String. CONCLUSIONS: This study provides a new perspective on the identification of novel detection strategies for benign and malignant PNs. We hope our findings can provide clues for the identification of benign and malignant PNs.

Preoperative brain MRI for clinical stage IA lung cancer: is routine scanning rational?

PURPOSE: Early detection and control of lung cancer brain metastases (BMs) are important. However, several guideline recommendations are inconsistent with regard to routine preoperative brain MRI, especially in patients with clinical stage IA lung cancer. Our study evaluated the value of preoperative brain MRI in patients with clinical stage IA lung cancer. METHODS: A retrospective analysis of patients with lung cancer was performed using a prospectively collected database. Clinical data and the results of brain MRI were collected and analyzed. RESULTS: Patients with pathologically proved primary lung cancer who underwent an MRI at initial diagnosis were identified (3392 patients). In total, 170 patients (5.0%) were diagnosed with BMs. The increased frequency of BMs was significantly associated with advanced clinical stage (P = 0.000) and pathological type (P = 0.011). BMs were detected in 11 out of 1595 patients with clinical stage IA lung cancer (0.7%). BMs were more common in patients with clinical stage cT1c lung cancer (1.9%) than those with clinical stage cT1a or cT1b (0.1%, odds ratio = 21.30, 95% confidence interval: 2.7-166.9, P = 0.000). All patients with stage IA lung cancer and BMs had solid lung lesions (P = 0.002). CONCLUSIONS: Preoperative brain MRI might help identify BMs in patients with lung cancer that has progressed beyond stage IA. In patients with clinical stage IA lung cancer, we do not recommend preoperative brain MRI, but it may potentially be beneficial in those with solid T1c cancers.

A B7-CD28 family based signature demonstrates significantly different prognoses and tumor immune landscapes in lung adenocarcinoma.

B7 family ligands and CD28 family receptors have complicated interaction for modulating immune functions. They play a central role in response to immunotherapy and outcome of patients with lung adenocarcinoma (LUAD). Thus, we analyzed B7-CD28 family gene expression profiles in LUAD and generated a signature to predict prognosis and immune host status. B7-CD28 family gene expression profiles and clinical data of LUAD from The Cancer Genome Atlas (TCGA) were analyzed. In the training cohort, prognostic association was assessed and then a prognostic signature was built with stepwise multivariable Cox analysis. The signature was validated by Kaplan-Meier and multivariable Cox analysis in several published gene expression datasets and a Fudan University cohort. Expression of immune cell populations and other immunotherapy predictors was further investigated. In TCGA LUAD cohort, eight B7-CD28 family genes had prognostic association with p values <0.05. Stepwise regression generated a gene signature including two genes, CD28 and CD276. Signature high-risk cases had worse overall survival (OS) and disease-free survival (DFS) in three published gene expression datasets and a Fudan University validation cohort. The B7-CD28 family based signature also significantly stratified OS and DFS in important clinical subsets, including stage I-II and EGFR mutant subsets. Signature high- and low-risk tumor had significantly different expressions of PD-L1 and tumor infiltrating leukocytes. The B7-CD28 family based signature demonstrates significantly different prognoses and tumor immune landscapes in LUAD. Whether it could serve as potential biomarkers for immunotherapy needs further investigation.

Does delayed esophagectomy after endoscopic resection affect outcomes in patients with stage T1 esophageal cancer? A propensity score-based analysis.

BACKGROUND: Although endoscopic resection (ER) may be sufficient treatment for early-stage esophageal cancer, additional treatment is recommended when there is a high risk of cancer recurrence. It is unclear whether delaying esophagectomy by performing and assessing the success of ER affects outcomes as compared with immediate esophagectomy without ER. Additionally, long-term survival after sequential ER and esophagectomy required further investigation. METHODS: Between 2011 and 2015, 48 patients with stage T1 esophageal cancer underwent esophagectomy after ER with curative intent at our institution. Two-to-one propensity score methods were used to identify 96 matched-control patients who were treated with esophagectomy only using baseline patient, tumor characteristics and surgical approach. Time from initial evaluation to esophagectomy, relapse-free survival, overall survival, and postoperative complications were compared between the propensity-matched groups. RESULTS: In the ER + esophagectomy group, the time from initial evaluation to esophagectomy was significantly longer than in the esophagectomy only group (114 vs. 8 days, p < 0.001). The incidence of dense adhesion (p = 0.347), operative time (p = 0.867), postoperative surgical complications (p = 0.966), and postoperative length of hospital stay (p = 0.125) were not significantly different between the groups. Moreover, recurrence-free survival and overall survival were also similar between the two groups (p = 0.411 and p = 0.817, respectively). CONCLUSIONS: Treatment of stage T1 esophageal cancer with ER prior to esophagectomy did not increase the difficulty of performing esophagectomy or the incidence of postoperative complications and did not affect survival after esophagectomy. These results suggest that ER can be recommended for patients with stage T1 cancer even if esophagectomy is warranted eventually.