Prognosis of esophageal squamous cell carcinoma patients with preoperative radiotherapy: Comparison of different cancer staging systems

Wang, Qifeng; Zhang, Wencheng; Liu, Xiao; Zhang, Xun; He, Jie; Feng, Qinfu; Zhou, Zongmei; Wang, Lvhua; Yin, Wenwu; Xiao, Zefen

doi:10.1111/1759-7714.12079

Cited by 11 publications

(13 citation statements)

References 12 publications

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“…Recently, reciprocal signaling between tumor cells and nerves were reported in vitro 7,9,13 . The receptors for nerve growth factors (NGFs) such as NTRK1 and NGFR are expressed on nerves, while NGF production in esophageal cancer cells is shown in vitro; further, esophageal cancer cells may induce neurite outgrowth of neuronal cells 2 . In these biological processes, neurotransmitters and neuropeptides secreted by nerves act as molecular determinants and promote invasion and metastasis 25 .…”

Section: Discussionmentioning

confidence: 99%

“…The dominant type of esophageal cancer in Eastern Asia is esophageal squamous cell carcinoma (ESCC). Despite recent improvements in diagnostic and therapeutic modalities, its prognosis remains poor, with an overall survival rate of 15%–25% and a high risk of metastases and recurrence 2,3 . Prognostication of ESCC using the Tumor, Node and Metastasis (TNM) classification system of the American Joint Committee on Cancer is widely accepted 4 .…”

Section: Introductionmentioning

confidence: 99%

“…Despite recent improvements in diagnostic and therapeutic modalities, its prognosis remains poor, with an overall survival rate of 15%-25% and a high risk of metastases and recurrence. 2,3 Prognostication of ESCC using the Tumor, Node and Metastasis (TNM) classification system of the American Joint Committee on Cancer is widely accepted. 4 Although the TNM system can provide a satisfactory prediction of survival, its accuracy is variable; for example, even for superficial tumors, ESCC showed significant rates of metastases and recurrences, which is related to poor outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic effect of perineural invasion in surgically treated esophageal squamous cell carcinoma

et al. 2021

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Background Although perineural invasion is a well known prognostic factor used in several cancers, its prognostic role in esophageal squamous cell carcinoma remains controversial. Here, we investigated the prognostic role of perineural invasion in surgically treated esophageal squamous cell carcinoma. Methods We retrospectively reviewed the medical records of 316 patients who underwent esophagectomy and lymph node dissection for esophageal squamous cell carcinoma between 2007 and 2016. Results Overall, 287 men (mean age: 62.73 ± 7.97 years) were included in the study. The median follow‐up period was 35.97 ± 30.99 months, perineural invasion was confirmed in 25 patients, and three‐year overall and disease‐free survival were significantly lower in the perineural invasion group than in the no‐perineural invasion group (75.9% vs. 40.0%, p < 0.001; 70.3% vs. 21.6%, p < 0.001). Cumulative incidences of locoregional recurrence and distant metastasis over three years were higher in the perineural invasion group (13.8% vs. 9.6%, p = 0.009 and 52.8% vs. 14.6%, p < 0.001). On performing multivariable analysis, perineural invasion, pathological stage, incomplete resection, and neoadjuvant therapy were adverse risk factors for disease‐free survival. The concordance index increased when perineural invasion was included in the model (0.712 vs. 0.723). On subgroup analysis, perineural invasion demonstrated a prognostic value in node‐negative patients (79.4% vs. 35.7%, p = 0.012). Conclusions Perineural invasion was found to be an adverse risk factor for disease‐free survival in surgically treated patients with esophageal squamous cell carcinoma. Close observation and individualized adjuvant therapy may be helpful for patients with perineural invasion.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prognostic effect of perineural invasion in surgically treated esophageal squamous cell carcinoma

et al. 2021

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“…Esophageal cancer ranks as the sixth leading cause of cancer-related mortality worldwide 1 and esophageal squamous cell carcinoma (ESCC) has a high global incidence, especially in central and southern Asia, accounting for approximately 80% of the total cases worldwide 2 . Despite recent advances in therapeutics against ESCC, the 5-year survival rate still ranges from 9% to 27.1% 3 - 5 and emerging therapeutic targets are in high demand. Esophageal mucosa with chronic irritation and inflammation has shown a tendency to develop into ESCC 2 ; therefore, it is important to identify and characterize the crucial role of the tumor microenvironment (TME) during disease progression.…”

Section: Introductionmentioning

confidence: 99%

FOXO1 promotes tumor progression by increased M2 macrophage infiltration in esophageal squamous cell carcinoma

et al. 2020

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Objective: The transcription factor forkhead box protein O1 (FOXO1) is critical for regulating cytokine and chemokine secretion. However, its function in the tumor microenvironment (TME) remains largely unexplored. In this study, we characterized the prognostic value of FOXO1 and the interaction between tumor-derived FOXO1 and M2 macrophages in esophageal squamous cell carcinoma (ESCC). Methods: FOXO1 expression and macrophage infiltration in clinical samples and mouse models were quantified using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry staining. Western blotting, qRT-PCR, and enzyme-linked immunosorbent assay were used to evaluate chemokine ligand 20 (CCL20) and colony stimulating factor 1 (CSF-1) expression in FOXO1(+) and FOXO1(-) tumor cells. Macrophage phenotypes were determined using qRT-PCR, flow cytometry, and RNA sequencing. Transcriptional activity was measured using chromatin immunoprecipitation (ChIP)-qPCR. Tumor viability was investigated using XTT proliferation and foci formation assays. Results: FOXO1 upregulation in tumor tissues was found to drive the polarization of M0 macrophages and infiltration of M2 macrophages into the TME, resulting in worse prognosis in ESCC patients. CSF-1, a vital factor inducing M0-to-M2 polarization, was upregulated via a FOXO1-mediated mechanism. RNA sequencing results corroborated that the FOXO1-induced macrophages exhibited similar molecular signatures to the IL4-stimulated M2 macrophages. The transwell assays showed that FOXO1 promoted the migration of M2 macrophages via CCL20 secretion, which could be inhibited using an anti-CCL20 antibody. FOXO1(+) tumor-induced M2 macrophages promoted tumor proliferation via the FAK-PI3K-AKT pathway and the PI3K inhibitor could effectively impede the oncogenical process. Conclusions: FOXO1 facilitated M0-to-M2 polarization and the recruitment of M2 macrophages in the TME via the transcriptional modulation of CCL20 and CSF-1. Our data deciphered the FOXO1-dependent mechanism in M2 macrophage infiltration in the TME of ESCC, which has implications for the development of novel prognostic and therapeutic targets to optimize the current treatment against ESCC.

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“…Among patients undergoing CCRT or preoperative CCRT, clinical TNM stage cannot accurately predict treatment response and prognosis 4,8,9,26 . In the Sichuan dataset (training) and the Fujian dataset (validation), the patients underwent CT examinations before and after treatment, with a post-treatment decrease in compactness (from ≥0.56 to <0.56) being associated with prolonged OS and PFS.…”

Section: Discussionmentioning

confidence: 99%

Tumor Compactness based on CT to predict prognosis after multimodal treatment for esophageal squamous cell carcinoma

Wang

Cao

Chen

et al. 2019

Sci Rep

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We aimed to establish a risk model using computed tomography-based compactness to predict overall survival (OS) and progression-free survival (PFS) after multimodal treatment for esophageal squamous cell carcinoma (ESCC). We extracted pre-treatment computed tomography-based tumor data (volume, surface area, and compactness) for 512 cases of ESCC that were treated at 3 centers. A risk model based on compactness was trained using Cox regression analyses of data from 83 cases, and then the model was validated using two independent cohorts (98 patients and 283 patients). The largest cohort (283 patients) was then evaluated using the risk model to predict response to radiotherapy with or without chemotherapy. In the three datasets, the pre-treatment compactness risk model provided good accuracy for predicting OS (P = 0.012, P = 0.022, and P = 0.003) and PFS (P < 0.001, P = 0.003, and P = 0.005). Patients in the low-risk group did not experience a significant OS benefit from concurrent chemoradiotherapy (P = 0.099). Furthermore, after preoperative concurrent chemoradiotherapy, the OS outcomes were similar among patients in the low-risk group who did and did not achieve a pathological complete response (P = 0.127). Tumor compactness was correlated with clinical T stage but was more accurate for predicting prognosis after treatment for ESCC, based on higher C-index values in all three datasets. The compactness-based risk model was effective for predicting OS and PFS after multimodal treatment for ESCC. Therefore, it may be useful for guiding personalized treatment.

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Prognosis of esophageal squamous cell carcinoma patients with preoperative radiotherapy: Comparison of different cancer staging systems

Cited by 11 publications

References 12 publications

Prognostic effect of perineural invasion in surgically treated esophageal squamous cell carcinoma

Prognostic effect of perineural invasion in surgically treated esophageal squamous cell carcinoma

FOXO1 promotes tumor progression by increased M2 macrophage infiltration in esophageal squamous cell carcinoma

Tumor Compactness based on CT to predict prognosis after multimodal treatment for esophageal squamous cell carcinoma

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