Esophageal Squamous Cell Cancer Patients Research Articles

Randomized controlled trial of intravenous sedation vs general anesthesia for esophageal dilation with percutaneous endoscopic gastrostomy in esophageal cancer patients.

Esophageal squamous cell cancer (ESCC) is mostly diagnosed in its later stages, when patients present with dysphagia and weight loss. Esophageal dilation with percutaneous endoscopic gastrostomy (PEG) is a common surgical procedure in patients with locally advanced ESCC because of tumor obstruction and enteral nutrition support during neoadjuvant or definitive concurrent chemoradiotherapy (CCRT). Esophageal dilation with PEG is widely performed under general anesthesia (GA) with endotracheal intubation. To determine the overall success rate of completing this procedure using intravenous (IV) sedation with dexmedetomidine (DEX) relative to GA and to compare its perioperative conditions, including procedure times, pain scores (visual analog scale), adverse events, and costs. SongklanagarindHospital, Faculty of Medicine, Prince of Songkla University, Thailand. Prospective randomized controlled trial (RCT) of locally advanced ESCC patients who had dysphagia and needed esophageal dilation with PEG between January 2020 and December 2021. Esophageal dilation (using a Savary-Gilliard dilator) and PEG were performed using the pull technique. Seventy patients were randomly assigned to either the DEX group (n = 34) or the GA group (n = 36). All patients in both groups underwent successful surgery. The DEX group had a significantly shorter procedure time, lower procedure cost, and lower total hospital cost than the GA group. However, there were no significant between-group differences in pain scores or length of hospital stay. There were no serious adverse events in either group; however, the GA group had some incidences of sore throat, transient hoarseness, and atelectasis. This study found that IV sedation with DEX during esophageal dilation with PEG was as effective and safe as using GA.

1H NMR-based metabolomics of paired tissue, serum and urine samples reveals an optimized panel of biofluids metabolic biomarkers for esophageal cancer.

The goal of this study was to establish an optimized metabolic panel by combining serum and urine biomarkers that could reflect the malignancy of cancer tissues to improve the non-invasive diagnosis of esophageal squamous cell cancer (ESCC). Urine and serum specimens representing the healthy and ESCC individuals, together with the paralleled ESCC cancer tissues and corresponding distant non-cancerous tissues were investigated in this study using the high-resolution 600 MHz 1H-NMR technique. We identified distinct 1H NMR-based serum and urine metabolic signatures respectively, which were linked to the metabolic profiles of esophageal-cancerous tissues. Creatine and glycine in both serum and urine were selected as the optimal biofluids biomarker panel for ESCC detection, as they were the overlapping discriminative metabolites across serum, urine and cancer tissues in ESCC patients. Also, the were the major metabolites involved in the perturbation of "glycine, serine, and threonine metabolism", the significant pathway alteration associated with ESCC progression. Then a visual predictive nomogram was constructed by combining creatine and glycine in both serum and urine, which exhibited superior diagnostic efficiency (with an AUC of 0.930) than any diagnostic model constructed by a single urine or serum metabolic biomarkers. Overall, this study highlighted that NMR-based biofluids metabolomics fingerprinting, as a non-invasive predictor, has the potential utility for ESCC detection. Further studies based on a lager number size and in combination with other omics or molecular biological approaches are needed to validate the metabolic pathway disturbances in ESCC patients.

Impact of Relative Dose Intensity of Docetaxel, Cisplatin, and 5-Fluorouracil Neoadjuvant Chemotherapy on Survival of Esophageal Squamous Cell Cancer Patients

Introduction: This study aimed to clarify the impact of the average relative dose intensity (RDI) of neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-NAC) for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Materials and Methods: To identify the optimal RDI, recurrence-free survival (RFS) and cumulative incidence function (CIF) for recurrence were calculated in low and high RDI groups with any cut-off points. The optimal RDI was defined as the highest RDI administered with a significant increase in either RFS or CIF. The clinicopathological characteristics of the two groups divided by optimal RDI were investigated. The preoperative prognostic factors associated with RFS were confirmed by multivariable Cox proportional hazards model. Results: Among the 150 eligible patients treated with DCF-NAC from 2010 to 2020, 3-year RFS and CIF were 56.3% and 37.8% in 90 patients in the less than 80% RDI group (<80% RDI) and 73.3% and 26.7% in 60 patients in the more than or equal to 80% RDI group (≥80% RDI), respectively. The optimal cut-off RDI was identified as 80%. The <80% RDI group included older individuals, a lower value of creatinine clearance, a higher Charlson Comorbidity Index, reduced RDI at first course, and grade 1–0 in the histopathological tumor response than the ≥80% RDI group. R0 resection and postoperative complication rates were equal in both groups. Cox proportional hazards model identified the response rate and RDI as predictors of RFS. Conclusion: An average RDI of more than or equal to 80% improved prognosis in patients receiving DCF-NAC for ESCC.

Prognostic value of proliferation markers Ki-67 and PCNA in esophageal squamous cell carcinoma.

Ki-67 and proliferating cell nuclear antigen (PCNA) are markers of proliferation used to assess the growth fraction of the cell population. The present study aimed to explore the prognostic value of these proliferative markers in patients with resected esophageal squamous cell cancer (ESCC) in a large cohort. A total of 807 patients with ESCC who underwent radical resection were retrospectively reviewed. Ki-67 and PCNA index were examined as the percentage of positively nuclear-stained cells among total number of cancer cells in three high-power fields by a pathologist who was blinded to the patients' history and outcome. Overall survival (OS) and disease-free survival (DFS) were estimated. The Cox regression model was used to evaluate the independent factor. The cut-off value as 60 and 80% for Ki-67 and PCNA were verified, respectively. Higher Ki-67 expression was associated with low differentiation and more lymph node metastasis. Higher PCNA expression was associated with elevated T stage. However, either expression of Ki-67 or PCNA was not correlated with OS and DFS. While in combination of Ki-67 and PCNA analysis, higher expression of these two proliferative markers predicted worse prognosis (median OS, 47 months versus 54 months, P = 0.04). Whatever the combined proliferative marker, differentiation, lymph node metastasis stage and vascular invasion act as factors in univariate survival analysis, but combined Ki-67 and PCNA is not an independent prognostic variable in multivariate analysis (P = 0.10). Our results suggest that proliferative markers of Ki-67 and PCNA may correlate with tumor stage but cannot act as independent predictor of prognosis in ESCC patients.

Combination of neutrophil-to-lymphocyte ratio and albumin concentration to predict the prognosis of esophageal squamous cell cancer patients undergoing esophagectomy

Combination of neutrophil-to-lymphocyte ratio and albumin concentration to predict the prognosis of esophageal squamous cell cancer patients undergoing esophagectomy

Post-treatment serum triglyceride: An effective biomarker for body fat mass and overall survival in esophageal squamous cell cancer patients treated with chemoradiotherapy.

Although lipids have been assessed for their possible roles in cancer survival prediction, studies on the association between serum triglyceride (TG) levels and the prognosis of esophageal squamous cell carcinoma (ESCC) patients are limited. This study aimed to evaluate whether serum TG is associated with outcomes in patients with ESCC and investigate any interaction between serum TG and clinical parameters, especially body fat mass. We conducted a prospective case study on patients diagnosed with ESCC between March 2012 and November 2018. We measured patients' serum TG levels before and after treatment. The association between serum TG and overall survival (OS) was evaluated using hazard ratios. We sought to determine a threshold point using optimal stratification. Survival analysis was performed using Kaplan-Meier curves and a Cox proportional hazards model. Of the 257 participants diagnosed with ESCC, 200 (77.8%) were men. Median follow-up time was 22.4 months (range 3.3-92.4 months). Using univariate Cox proportional hazard analysis and subsequent multivariate analysis, post-TG levels, Karnofsky performance scores, T stages, and chemotherapy cycles were shown to be independent prognostic factors for OS (p < 0.05). The post-TG cut-off point to best classify patients with respect to time to mortality was 1.47 mmol/L. A post-TG level of ≥ 1.47 mmol/L could independently predict a better OS (hazard ratio: 0.55, 95% confidence interval: 0.37-0.79). The associations were consistent across the subtypes of clinical parameters. Furthermore, the post-body mass index, post-subcutaneous adipose tissue area, post-visceral adipose tissue area, post-total adiposity tissue area, and post-total adipose density exhibited a strong positive association with post-TG levels. Post-TG levels were found to be a significant positive prognostic biomarker for body fat mass and OS in ESCC patients.

The predictive value of peripheral blood cells and lymphocyte subsets in oesophageal squamous cell cancer patients with neoadjuvant chemoradiotherapy.

Neoadjuvant chemoradiotherapy (nCRT) is a standard treatment option for patients with stage III oesophageal cancer. Approximately 30% of oesophageal cancer patients will have a pathological complete response (pCR) after nCRT. However, available clinical methods cannot accurately predict pCR for patients. We aimed to find more indicators that could be used to predict the pathological response to nCRT. A total of 84 patients with stage III oesophageal squamous cell cancer were enrolled in this study. Ten patients failed to have surgery as a result of progressive disease (PD). Among the patients who underwent surgery, 32 patients had a pathologic complete response (pCR), whereas 42 patients showed no or partial response (npCR) after nCRT. Routine blood test results and lymphocyte subset assessments before and after nCRT were retrospectively analysed. Univariate and multivariate analyses were used to identify independent predictors of the clinical curative effect of nCRT. Eventually, nomograms were established for predicting the PD and pCR rates. The numbers of lymphocytes, B lymphocytes, T lymphocytes, Th lymphocytes, Ts lymphocytes, and NK cells and the percentages of B lymphocytes and NK cells were decreased significantly after nCRT (P < 0.0001), whereas the percentages of T lymphocytes and Ts lymphocytes increased (P < 0.0001). Univariate analysis showed that age, the length of the lesion, the level of haemoglobin before nCRT, and the amount of change in haemoglobin were related to PD, and the percentage of NK cells after nCRT was related to pCR. Multivariate logistic analysis demonstrated that the length of the lesion, the neutrophil-to-lymphocyte ratio (NLR) before nCRT, and the amount of change in haemoglobin were independent predictors of PD, whereas the percentage of NK cells after nCRT was an independent predictor of pCR. Lymphocyte subsets changed dramatically during nCRT, and these changes together with baseline and posttreatment lymphocyte subsets have predictive value in determining the response to nCRT for oesophageal cancer.

Prognostic value of nutritional and inflammatory indicators in females with esophageal squamous cell cancer: A propensity score matching study.

Background: Esophageal squamous cell cancer (ESCC) is a disease with a male predominance. Accordingly, the applicability of prognostic indicators values previously set for the general population with ESCC has not been reported for determining the physical state in females. Methods: Patients with ESCC were pooled from 2009 to 2017 at Sichuan Cancer Hospital. We determined the differences in the nutritional and inflammatory indicators between gender by sex-stratified survival analysis in all cohorts (n = 2,660) and matching cohorts (n = 483 pairs) separately. Propensity score matching (PSM) was employed to eliminate selection bias between genders. We further performed the prognostic value of total cholesterol (TC) by subgroup analysis in the female cohort. The area ROC curve was used to assess the predictive performance of TC in females. Results: There were a total of 2,660 patients with ESCC, of whom 2,173 (81.7%) were male and 487 (18.3%) were female. Before PSM, the prognostic nutritional index was an independent factor for OS in males but not in females. For cohort with or without matching, TC was an independent prognostic factor in females not for males. Furthermore, female patients with high TC level had significant poor OS in stages III and IV. The AUCs of TC were 0.63 and 0.70 for predicting 3- and 5-year OS, respectively. Conclusion: Based on a much larger cohort, we confirmed that gender was a significant prognostic factor for ESCC patients. Interestingly, we found a significant difference in TC related to ESCC prognosis between genders. Collectively, TC might be an independent prognostic factor in females with ESCC.

Molecular Imaging of Fibroblast Activity in Radiation-Induced Acute Myocardial Damage Using a [18F]AlF-Labeled Fibroblast Activation Protein Inhibitor, FAPI-04

<h3>Purpose/Objective(s)</h3> A previous retrospective analysis revealed increased [¹⁸F]AlF-NOTA-FAPI uptake in myocardial tissue of patients with esophageal squamous cell cancer (ESCC) treated with concurrent chemoradiotherapy (CCRT). The present study investigated and verified the feasibility of [¹⁸F]AlF-NOTA-FAPI positron emission tomography (PET)/computed tomography (CT) imaging for detecting radiation-induced myocardial damage (RIMD). <h3>Materials/Methods</h3> Myocardial FAPI uptake was analyzed before radiotherapy and during radiotherapy (36–50 Gy) in 13 ESCC patients treated with CCRT. In an animal study, a single dose of 50 Gy was delivered to the cardiac apex of female Wistar rats using conformal radiotherapy. RIMD model rats were scanned with [¹⁸F]AlF-NOTA-FAPI PET/CT weekly for 12 weeks, and then MRI was conducted. Dynamic, competition, and [¹⁸F]FDG PET/CT studies were performed on RIMD rats at 5 weeks post-radiation, and histopathological analyses were conducted. <h3>Results</h3> Three patients showed potentially increased FAPI uptake in myocardial tissue after radiotherapy. In the RIMD rat model, a significant increase in FAPI uptake in the damaged myocardium was observed from the 2nd week post-radiation exposure, with peak values observed in the 5th week. Significantly more intense tracer accumulation was observed in the damaged myocardial region than in remote myocardial tissue, as identified by decreased [¹⁸F]FDG uptake and confirmed by autoradiography, Masson's trichrome staining and immunohistochemical staining. The left ventricular ejection fraction (LVEF) remained unchanged from baseline at the 3rd week post-radiation exposure but was remarkably decreased compared with that in the control group at the 8th week. <h3>Conclusion</h3> An increase in myocardial uptake of [¹⁸F]AlF-NOTA-FAPI occurred in patients with ESCC after radiotherapy. These results indicated that FAPI PET/CT imaging can detect RIMD noninvasively and before a decrease in LVEF is detected, indicating the clinical potential of FAPI as a radiotracer for in vivo imaging of RIMD.

Genetic variant of ADH1C for predicting survival in esophageal squamous cell cancer patients who underwent postoperative radiotherapy.

Background: Single nucleotide polymorphisms (SNPs) of essential enzymes for alcohol metabolism ADH1B, ADH1C, and ALDH2 are commonly regarded as genetic biomarkers for esophageal squamous cell carcinoma (ESCC) susceptibility. However, there have not been any reports on relations between SNPs of these genes and the prognosis of postoperative radiotherapy in ESCC. The current study aimed to understand the associations between gene variants of alcohol metabolism and adjuvant radiotherapy’s prognosis in ESCC. Methods: This study retrospectively analyzed 110 ESCC patients from our institution who received adjuvant radiotherapy after surgery. The SNPs of ADH1B rs1229984, ADH1C rs1789924, and ALDH2 rs671 were detected by Sanger sequencing using formalin-fixed paraffin-embedded tumor samples. A nomogram was drawn based on prognostic factors associated with overall survival (OS). Results: ADH1C rs1789924 (C>T) was associated with poor DFS and OS in ESCC patients undergoing adjuvant radiotherapy. Multivariate analysis showed that ADH1C rs1789924 (C>T) was one of the independent prognosis factors of DFS and OS. However, the genotypes of ADH1B SNP rs1229984 and ALDH2 rs671 were not associated with differences in the PFS and OS of these patients. Compared with the AJCC staging system, the nomogram containing the ADH1C genotype can more effectively and accurately predict the survival time of ESCC after surgery and adjuvant radiotherapy. Conclusion: ADH1C rs1789924 might be a prognostic genetic biomarker for ESCC patients undergoing surgery and postoperative radiotherapy.

Early detection of radiation-induced myocardial damage by [18F]AlF-NOTA-FAPI-04 PET/CT imaging.

Retrospective analysis revealed increased [18F]AlF-NOTA-FAPI-04 uptake in the myocardium of patients with esophageal squamous cell cancer (ESCC) treated with concurrent chemoradiotherapy (CCRT). This study investigated and verified the feasibility of [18F]AlF-NOTA-FAPI-04 PET/CT for detecting radiation-induced myocardial damage (RIMD). Myocardial FAPI uptake was analyzed before and during radiotherapy in thirteen ESCC patients treated with CCRT. In the animal study, a single dose of 50Gy was delivered to the cardiac apex of Wistar rats (24 rats, including 16 RIMD model rats and 8 control model rats). RIMD model rats were scanned with [18F]AlF-NOTA-FAPI-04 PET/CT weekly for 12weeks, and left ventricular ejection fraction (LVEF) was measured by magnetic resonance imaging. Dynamic, blocking, and [18F]FDG PET/CT studies (4 rats/group) were performed on RIMD rats at 5weeks post-radiation, and histopathological analyses were conducted. Increased FAPI uptake in the myocardium was found after CCRT (1.53 ± 0.53 vs 1.88 ± 0.70, P = 0.015). In RIMD rats, significantly increased FAPI uptake in the damaged myocardium was observed from the 2nd week post-radiation exposure and peaked in the 5th week. Significantly more intense tracer accumulation was observed in the damaged myocardium than in the remote myocardium, as identified by decreased [18F]FDG uptake and confirmed by autoradiography, hematoxylin-eosin, Masson's trichrome, and immunohistochemical staining. The LVEF remained unchanged at the 3rd week post-radiation exposure but was remarkably decreased compared with that in the control group at the 8th week. Through clinical phenomena and animal experimental studies, this study indicated that [18F]AlF-NOTA-FAPI-04 PET/CT imaging can detect RIMD noninvasively and before a decrease in LVEF, indicating the clinical potential of [18F]AlF-NOTA-FAPI-04 as a PET/CT tracer for early monitoring of RIMD.

Assessment of durable chemoimmunotherapy response via circulating tumor DNA in advanced esophageal squamous cell carcinoma.

Immune checkpoint inhibitor (ICI)‐based therapies have shown promising advances for the first‐line treatment of advanced or metastatic esophageal cancer (EC). However, few studies concerning the identification of patients who achieve durable response from ICIs have been previously reported. In the present study, pre‐ and on‐treatment plasma circulating tumor DNA (ctDNA) were analyzed in 10 patients with advanced esophageal squamous cell cancer (ESCC) receiving first‐line chemoimmunotherapy. Patients with decreased molecular tumor burden index (mTBI) >7% experienced longer progression‐free survival (PFS) and durable clinical benefit (DCB, PFS ≥ 6 months). In addition, five patients showed stable disease at first scan, all three patients with decreased mTBI > 7% achieved DCB, while two cases with decreased mTBI ≤ 7% experienced non‐DCB. Our results demonstrate that ctDNA monitor might help identify which ESCC patients respond to chemoimmunotherapy.

Long-Term Clinical Outcomes and Safety Analysis of Superficial Esophageal Cancer Patients Treated with Definitive or Adjuvant Radiotherapy.

Simple SummaryFor superficial esophageal cancer, many tumor features have been identified as risk factors for lymph node metastasis, including depth of invasion, tumor size, the presence of lymphovascular invasion, etc. In such cases, endoscopic resection (ER) alone is not adequate for treatment coverage, and additional radiotherapy (RT)/concurrent chemoradiotherapy (CCRT) merits further investigation. On the other hand, esophagectomy has a high cure rate for early stage esophageal squamous cell cancer (ESCC); however, there are concerns of treatment complications and loss of esophagus preservation. Hence, definitive RT/CCRT may be a promising treatment alternative to esophagectomy, especially for those who are unable or unwilling to receive surgery. We retrospectively analyzed outcomes of patients with T1N0M0 staged ESCC treated with ER + RT/CCRT or RT/CCRT. We conclude that definitive or adjuvant RT/CCRT is an effective treatment alternative for superficial ESCC patients with satisfactory clinical outcomes and acceptable toxicities.(1) Background: The role of radiotherapy (RT) in superficial esophageal squamous cell cancer (ESCC) remains unclear. The objective of our study was to perform a detailed outcome and safety analysis of RT as a definitive or adjuvant treatment for T1N0M0 staged ESCC patients. (2) Methods: A total of 55 patients treated with endoscopic resection (ER) + RT/concurrent chemoradiotherapy (CCRT) or RT/CCRT from January 2011 to June 2021 were included in this study. Eighteen patients with risk factors received ER + RT/CCRT, and thirty-seven patients solely received RT/CCRT. Kaplan–Meier curves were used to calculate the clinical outcomes, and toxicities were scored. (3) Results: The median follow-up time was 51.9 months. The estimated 5-year local recurrence-free survival (LRFS) and overall survival (OS) were 88.9% and 94.4% in the ER + RT/CCRT group and 91.8% and 91.7% in the RT/CCRT group. The predominant failure pattern was in-field local failure (5.5%, 3/55), with one patient in the ER + RT/CCRT group and two patients in the RT/CCRT group. One patient (1.8%, 1/55) had lung metastasis in the RT/CCRT group. The most common toxicities were Grades 1–2 in all patients, including esophagitis (74.5%, 41/55), myelosuppression (49.1%, 27/55) and esophageal stricture after RT (27.3%, 15/55). Two patients (11.1%, 2/18) and four patients (10.8%, 4/37) had Grade 3 esophageal stricture after RT in the ER + RT/CCRT group and RT/CCRT group, respectively. No patients experienced a Grade 4 or higher toxicity, and there were no treatment-related deaths. (4) Conclusions: Definitive or adjuvant RT/CCRT is an effective treatment alternative for superficial ESCC patients with satisfactory clinical outcomes and acceptable toxicities.

CT-based radiomics nomogram may predict local recurrence-free survival in esophageal cancer patients receiving definitive chemoradiation or radiotherapy: A multicenter study

Background and purposeTo establish and validate a contrast-enhanced computed tomography-based hybrid radiomics nomogram for prediction of local recurrence-free survival (LRFS) in esophageal squamous cell cancer (ESCC) patients receiving definitive (chemo)radiotherapy in a multicenter setting. Materials and methodsThis retrospective study included 302 ESCC patients from Xijing Hospital receiving definitive (chemo)radiotherapy, which were randomly assigned to the training (n = 201) and internal validation sets (n = 101). And 74 and 21 ESCC patients from the other two centers were used as the external validation set (n = 95). A hybrid radiomics nomogram was established by integrating clinical factors, radiomic signature and deep-learning signature in training set and was tested in two validation sets. ResultsThe deep-learning signature showed better prognostic performance than radiomic signature for predicting LRFS in training (C-index: 0.73 vs 0.70), internal (Cindex: 0.72 vs 0.64) and external validation sets (C-index: 0.72 vs 0.63), which could stratify patients into high and low-risk group with different prognosis (cut-off value: −0.06). Low-risk groups had better LRFS than high-risk groups in training (p < 0.0001; 2-y LRFS 71.1% vs 33.0%), internal (p < 0.01; 2-y LRFS 58.8% vs 34.8%) and external validation sets (p < 0.0001; 2-y LRFS 61.9% vs 22.4%), respectively. The hybrid radiomics nomogram established by integrating radiomic signature, deep-learning signature with clinical factors including T stage and concurrent chemotherapy outperformed any one or two combinations in training (C-index: 0.82), internal (Cindex: 0.78), and external validation sets (C-index: 0.76). Calibration curves showed good agreement. ConclusionsThe hybrid radiomics based on pretreatment contrast-enhanced computed tomography provided a promising way to predict local recurrence of ESCC patients receiving definitive (chemo)radiotherapy.

Local Ablative Treatment Improves Survival in ESCC Patients With Specific Metastases, 2010-2016: A Population-Based SEER Analysis.

BackgroundWe aimed to explore the role of local ablative treatment (LAT) in metastatic esophageal squamous cell cancer (ESCC) patients who received chemotherapy and identify patients who will most likely benefit.MethodsWe analyzed data of metastatic ESCC patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. The chi-square test was used to evaluate the unadjusted clinicopathological categorical variables between the two groups. Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic factors of overall survival. Propensity score matching (PSM) was used to adjust the differences between the two groups.ResultsOverall, 720 metastatic ESCC patients treated with chemotherapy were analyzed in this study; 63.2% of patients (n = 455) received LAT, including radiotherapy (n = 444), primary site surgery (n = 12), or lymph node dissection (n = 27). Gender (HR = 1.220, 95% CI: 1.024–1.453, p = 0.026), bone metastases (HR = 1.559, 95% CI: 1.292–1.882, p < 0.001), and liver metastases (HR = 1.457, 95% CI: 1.237–1.716, p < 0.001) were independent prognostic factors in the entire population. However, LAT was not an independent prognostic factor. Further subgroup analyses showed that LAT improved OS from 8.0 months to 10.0 months in patients with metastases other than bone/liver (HR = 0.759, 95% CI: 0.600–0.961, p = 0.022). LAT was not a prognostic factor in patients with bone/liver metastases (HR = 0.995, 95% CI: 0.799–1.239, p = 0.961). After PSM, the median OS was 8.0 months (95% CI: 7.2–8.8 months) and patients who received LAT had a better OS than patients without LAT (HR = 0.796, 95% CI: 0.653–0.968, p = 0.023). Patients with metastases other than bone/liver could benefit from LAT compared with those with bone/liver metastases.ConclusionsOur study indicated that metastatic ESCC patients with metastases other than bone/liver could derive additional benefit from LAT with systemic chemotherapy.

Sarcopenia is associated with prognosis in patients with esophageal squamous cell cancer after radiotherapy or chemoradiotherapy

BackgroundThis study aimed to determine the prognostic value of the sarcopenia on the progression free survival (PFS) and overall survival (OS) of esophageal squamous cell cancer (ESCC) patients who received radiotherapy (RT) or chemoradiotherapy (CRT).MethodsData on clinicopathological characteristics and nutritional parameters were analyzed and correlated with PFS and OS, retrospectively. Skeletal muscle, subcutaneous, visceral and total fat tissue cross-sectional areas were evaluated on CT images at the midpoint of the 3rd lumbar vertebrae. A total of 213 patients were enrolled in this study.ResultsSarcopenia was significantly associated with subcutaneous fat content. The univariate analysis demonstrated that OS was superior in patients with non-sarcopenia, non-alcohol, NRI ≥ 100, albumin ≥ 40 g/L, TATI > 83.0, SATI > 27.8, VATI > 49, non-anemia, cervical and upper-thoracic ESCC, T stage 1–2, N stage 0–1 and TNM stage I–II. In the multivariate analysis, sarcopenia, albumin, N stage and TNM stage were identified as independent prognostic factors of survival. This study demonstrated that sarcopenia was related to worse PFS and OS in patients with ESCC who received RT or CRT.ConclusionsSarcopenia is considered to be a useful predictor in patients with ESCC who received RT or CRT. This study also provided a conceptual basis for further prospective research on the application of the sarcopenia for patients receiving RT or CRT for intermediate- and advanced-stage ESCC.

Utility of Concurrent Surgical Treatment Strategy with Thoracoscopic Esophagectomy for Patients with Synchronous Esophageal and Head and Neck Cancer.

Background: Patients with esophageal squamous cell cancer (ESCC) have a high frequency to coincide with head and neck cancer (HNC). This study aims to analyze the treatment results and prognosis of patients with synchronous ESCC and HNC. Methods: From January 2016 to December 2019, 5 patients underwent concurrent surgical resection of synchronous ESCC and HNC in our institution. We retrospectively reviewed the surgical outcomes and prognosis of these patients with synchronous ESCC and HNC (HNEC group) and compared the results with those of 20 patients who underwent esophagectomy with three regional lymph node dissections for ESCC during the same period (EC group). Results: The locations of HNCs were pharynx/tongue (4/1) and the clinical stages were Stage IV in all patients. Meanwhile, the clinical stages of ESCCs were Stages 0/I/II/III (1/1/2/1). All patients underwent thoracoscopic esophagectomy. The surgical procedures concurrently performed for HNC were pharyngolaryngectomy with free jejunum transfer in 3 patients, wide tongue and mandibular segment resection with mandibular reconstruction in 1 patient, and mandibular transection with radial forearm flap reconstruction in 1 patient. There was no significant difference in the frequency of postoperative complication between these two groups. The HNEC group had a significantly shorter recurrence-free survival than the EC group (P = .046). Conclusion: Head and neck surgery with thoracoscopic esophagectomy can be safely performed concurrently with local control. The risk of recurrence is higher in ESCC patients with HNC; therefore, it is important to move on to adjuvant therapy without delay.

Peritumoral CD16b positive-neutrophil accumulation strongly correlates with regional lymph node metastasis in thoracic esophageal squamous cell cancer

BackgroundThe mechanism underlying cancer cell metastasis from the tumor to regional lymph nodes is not yet fully understood. We hypothesized that peritumoral neutrophil accumulation promotes regional lymph node metastasis in thoracic esophageal squamous cell cancer. MethodsBetween 2010 and 2019, 126 thoracic esophageal squamous cell cancer patients received curative (R0) esophagectomy without preoperative treatment in our hospital. Using paraffin-embedded resected tumors, we performed immunohistochemical analysis of CD16b-positive neutrophil accumulation in the peritumoral area, which was defined as a 1-mm region centered on the border separating the malignant cell nests from the host tissue. The relationship between the density of peritumoral CD16b staining and pathological lymph node metastasis or 5-year overall survival was evaluated. ResultsAlthough the clinicopathological characteristics of CD16b-high and CD16b-low patients did not differ, greater pathological lymph node metastasis (P < .001) and lymphatic invasion by the tumor (P = .024) and a poorer 5-year survival (P = .010) were seen in CD16b-high patients. Moreover, CD16b-positive neutrophil density was generally higher in the peritumoral area than within the tumor itself. Univariate and multivariate analyses showed that CD16b-positive neutrophil accumulation was an independent factor for lymph node metastasis with an odds ratio >25 (P < .001). On the other hand, blood neutrophil counts did not correlate with lymph node metastasis. ConclusionPeritumoral accumulation of CD16b-positive neutrophils is an independent factor strongly correlated with lymph node metastasis in thoracic esophageal squamous cell cancer.

Identification of a Ten-Gene Signature of DNA Damage Response Pathways with Prognostic Value in Esophageal Squamous Cell Carcinoma.

Molecular prognostic signatures are critical for treatment decision-making in esophageal squamous cell cancer (ESCC), but the robustness of these signatures is limited. The aberrant DNA damage response (DDR) pathway may lead to the accumulation of mutations and thus accelerate tumor progression in ESCC. Given this, we applied the LASSO Cox regression to the transcriptomic data of DDR genes, and a prognostic DDR-related gene expression signature (DRGS) consisting of ten genes was constructed, including PARP3, POLB, XRCC5, MLH1, DMC1, GTF2H3, PER1, SMC5, TCEA1, and HERC2. The DRGS was independently associated with overall survival in both training and validation cohorts. The DRGS achieved higher accuracy than six previously reported multigene signatures for the prediction of prognosis in comparable cohorts. Furtherly, a nomogram incorporating DRGS and clinicopathological features showed improved predicting performance. Taken together, the DRGS was identified as a novel, robust, and effective prognostic indicator, which may refine the scheme of risk stratification and management in ESCC patients.

CircGOT1 promotes cell proliferation, mobility, and glycolysis-mediated cisplatin resistance via inhibiting its host gene GOT1 in esophageal squamous cell cancer

ABSTRACT Esophageal squamous cell cancer (ESCC) is a prevalent malignant cancer with high incidence and fatality rate. Surging evidences have revealed that circular RNAs (circRNAs) act key role in ESCC tumorigenesis and progression. Therefore, the purpose of this study is to explore the role and regulatory mechanism of a novel circGOT1 in ESCC. In the present study, the transcriptional expression of circGOT1, miR-606 and GOT1, and the epithelial–mesenchymal transition (EMT) and apoptosis-related markers were examined by quantitative PCR. The protein levels of GOT1 and glycolysis-related proteins were detected by Western blotting. In addition, the glycolytic levels were determined via measuring glucose uptake, lactate production, and ATP levels. Then, the function experiments and rescue experiments were used to investigate the function and mechanism of circGOT1 in ESCC. In addition, RNA immunoprecipitation, pull-down, and luciferase activity reporter gene assays were used to analyze the circGOT1/miR-606/GOT1 axis. The xenograft mouse mode was used to determine the function of circGOT1 in vivo. Here, we identified that circGOT1 and GOT1 upregulate, whereas miR-606 was reduced in ESCC tissues and cell lines. High circGOT1 and GOT1 expression associated with poor survival and worse prognosis of ESCC patients, but miR-606 revealed opposite traits. Mechanically, circGOT1 sponged miR-606 to promote GOT1, which induced cell proliferation, migration, aerobic glycolysis, and cisplatin resistance. The tumor growth was reduced by circGOT1 inhibition in xenograft mouse. Our results indicate the oncogene role of circGOT1 in ESCC via an endogenous competition RNA (ceRNA) mechanism to promote GOT1 expression via sponging miR-606.