Recurrence Of Esophageal Squamous Cell Carcinoma Research Articles

The Expression of TP63 as a Biomarker of Early Recurrence in Resected Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy.

Esophageal cancer ranks among the ten most common cancers worldwide. Despite the adoption of neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by surgery as the standard treatment approach in recent years, the local recurrence rate remains high. In this study, we employed RNA-seq to investigate distinctive gene expression profiles in esophageal squamous cell carcinoma (ESCC) with or without recurrence following a standard treatment course. Our findings indicate that recurrent ESCC exhibits heightened keratinizing and epidermis development activity compared to non-recurrent ESCC. We identified TP63 as a potential candidate for distinguishing clinical outcomes. Furthermore, immunohistochemistry confirmed the trend of TP63 overexpression in ESCC recurrence. Patients with elevated TP63 expression had poorer overall survival and lower 3-year recurrence-free survival. This study underscores the potential of TP63 as a biomarker for detecting cancer recurrence and suggests its role in guiding future treatment options.

The relationship between the treatment course and prognosis of oligometastasis after esophageal squamous cell carcinoma resection.

The concept of oligometastasis, which represents limited metastatic disease, has recently gained interest, accompanied by a more detailed classification. This study aims to investigate the relationship between the treatment course and prognosis in patients with a recurrence of esophageal squamous cell carcinoma (ESCC) after curative esophagectomy. 126 patients with ESCC recurrence after curative resection were enrolled in this study. Oligometastasis was defined as fewer than five recurrences in a single organ. Patients were classified as having oligometastatic recurrence (OLR) or polymetastatic recurrence (PLR). Patients were further classified into four subgroups according to lesion progression: persistent oligorecurrence (PER-OLR), converted polyrecurrence (CON-PLR), induced oligorecurrence (IND-OLR), and persistent polyrecurrence (PER-PLR). We analyzed the relationship between the recurrence patterns and prognosis according to the progression of oligometastatic lesions. OLR was identified in 58 (46%) of 126 patients with recurrence. Patients with OLR had a significantly better prognosis than those with PLR (P < 0.0001). A further subgroup analysis revealed that patients who underwent IND-OLR had a similar prognosis to those who underwent PER-OLR. This study suggests that OLR is a prognostic factor after recurrence following resection of ESCC and that PLR can be converted to OLR by therapeutic intervention to achieve a long-term survival.

Correlation between histopathological response by neoadjuvant DCF therapy and the clinical efficacy of palliative platinum-containing regimens for recurrent ESCC.

272 Background: Docetaxel and cisplatin, 5-FU (DCF) therapy has established as the standard neoadjuvant treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC) based on the results of the JCOG1109 study. If patients showed recurrence of ESCC after neoadjuvant DCF therapy, platinum-containing regimens were used as palliative treatment in the clinical practice. However, there were no data of correlation between histopathological response by neoadjuvant DCF therapy and clinical efficacy of palliative platinum-containing regimens for recurrent ESCC. Methods: We retrospectively reviewed patients with ESCC who received neoadjuvant DCF therapy and R0 resection between Feb 2014 to June 2022 in our hospital. We evaluated histopathological response by neoadjuvant DCF therapy based on the Japanese Classification of Esophageal Cancer 12th (Grade 0: ineffective, Grade 1: slightly effective, Grade 2: moderately effective, Grade 3: markedly effective [pT0]) and objective response rate (ORR), progression-free survival (PFS) during platinum-containing regimens as clinical efficacy outcomes. We analyzed the correlation between histopathological response and ORR, PFS using Fisher’s exact tests and the log-rank tests. In addition, we analyzed clinical factors related to clinical efficacy of palliative chemotherapy using Cox proportional hazards models. Results: In this study, 398 patients received neoadjuvant DCF therapy and we identified 88 eligible patients with recurrence. Among 88 patients, 33 patients initially received palliative chemotherapy and analyzed. Patients’ characteristics were followed; Male/Female: 26 (78.8%)/7 (21.2%), median age (range): 64 (46-76) years, PS 0/1/2: 1 2(36.4%)/17 (51.5%), 4 (12.1%). Histopathological response 0/1/2/3 were in 1 (3.0%)/23 (69.7%)/7 (21.2%)/2 (6.1%) patients, respectively. Among these 33 patients, 23 patients received platinum-containing regimens. In the patients who received palliative chemotherapy, the ORR were 34.8% (8/23) in histopathological response 0/1 group and 44.4% (4/9) in histopathological response 2/3 group, with no statistical difference (p = 0.696). The median PFS was 2.43 (95%CI: 2.33-2.53) months in histopathological response 0/1 group and 4.04 (95%CI: 0-10.77) months in histopathological 2/3 group (HR[95%CI]: 1.121 [0.413-3.043]). Multivariate analysis using Cox proportional hazards models revealed chemotherapy-free-interval (CFI) &lt; 6 months (HR[95%CI]: 3.594 [1.027–12.580]) was independent prognostic factor, whereas histopathological response didn’t show the significance (HR[95%CI]: 0.723 [0.195–2.678]). Conclusions: Histopathological response by neoadjuvant DCF therapy did not affect the efficacy of platinum-containing regimens for recurrent ESCC, while CFI might be the prognostic factors.

Impact of non-obese metabolic dysfunction-associated fatty liver disease on risk factors for the recurrence of esophageal squamous cell carcinoma treated with endoscopic submucosal dissection: A multicenter study.

Metabolic dysfunction is a risk factor for esophageal squamous cell carcinoma (ESCC). We investigated the impact of the recently proposed metabolic dysfunction-associated fatty liver disease (MAFLD) and its subtypes on ESCC recurrence after endoscopic treatment. This multicenter observational cohort study enrolled consecutive patients newly diagnosed with ESCC after endoscopic treatment. Patients were classified into MAFLD or non-MAFLD groups. The MAFLD group was further classified into non-obese and obese MAFLD groups with a body mass index cutoff value of 25kg/m2 . The impact of MAFLD on the recurrence of ESCC was evaluated using a decision tree algorithm and random forest analysis. A total of 147 patients (average age 69years; male:female, 127:20; observational period, 2.4years) were enrolled. The 1-, 3-, and 5-year recurrence rates were 2.0%, 21.1%, and 33.7%, respectively. Independent risk factors for the recurrence of ESCC were MAFLD (HR 2.2812; 95% confidence interval 1.0497-4.9571; p=0.0373), drinking status, and smoking status. Metabolic dysfunction-associated fatty liver disease was identified as the second most important classifier for recurrence, followed by drinking status. The cumulative incidence of ESCC recurrence was higher in the MAFLD group than in the non-MAFLD group. In a subanalysis, the cumulative incidence of recurrence was significantly higher in the non-obese than in the obese MAFLD group among abstainers/non-drinkers. Directed acyclic graphs revealed that MAFLD directly contributes to ESCC recurrence. MAFLD was independently and directly associated with ESCC recurrence after endoscopic treatment; a high recurrence rate was observed in patients with non-obese MAFLD. Metabolic dysfunction-associated fatty liver disease may identify patients at high risk for ESCC recurrence.

Circulating Tumor DNA Dynamics as Prognostic Markers in Locally Advanced and Metastatic Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is a deadly disease with frequent recurrence. There are unmet needs for prognostic biomarkers for dynamically monitoring disease progression and detecting minimal residual disease. To examine whether circulating tumor DNA is clinically useful as a prognostic biomarker for ESCC recurrence and patient survival. This single-center, population-based cohort study consecutively enrolled 147 patients receiving curative (n = 74) or palliative (n = 73) treatment at the surgery and clinical oncology departments of Queen Mary Hospital in Hong Kong from August 1, 2016, to September 31, 2021. Patients were followed up for 2 years. Plasma samples were collected at different longitudinal time points for a prospective circulating tumor DNA (ctDNA) next-generation sequencing profiling study of 77 actionable genes. Patients were treated with up-front surgery, neoadjuvant chemoradiotherapy plus surgery with or without adjuvant therapy, or palliative chemotherapy (CT). Detection of circulating tumor DNA (ctDNA), progression-free survival (PFS), and overall survival (OS). A total of 478 serial plasma samples from 147 patients with locoregional or metastatic ESCC were prospectively analyzed. Among the 74 patients in the curative group (median [range] age, 66 [46-85] years; 56 [76.0%] male), 44 (59.5%) relapsed and 36 (48.6%) died. For patients receiving curative surgical treatment, a high ctDNA level (hazard ratio [HR], 7.84; 95% CI, 1.87-32.97; P = .005) and ctDNA alterations (HR, 5.71; 95% CI, 1.81-17.97; P = .003) at 6 months postoperation were independently associated with poor OS. Among patients receiving neoadjuvant chemoradiotherapy, postneoadjuvant ctDNA alterations were associated with poor PFS (HR, 3.16; 95% CI, 1.17-8.52; P = .02). In the 73 patients in the palliative group (median [range] age, 63 [45-82] years; 63 [86.0%] male), 71 (97.3%) had disease relapse and 68 (93.2%) died. Detectable pre-CT NFE2L2 alterations were independently associated with PFS (HR, 2.99; 95% CI, 1.35-6.61; P = .007) and OS (HR, 28.39; 95% CI, 7.26-111.03; P = 1.52 × 10-6), whereas high ctDNA levels (HR, 2.41; 95% CI, 1.18-4.95; P = .02) and alterations in pre-cycle III ctDNA (HR, 1.99; 95% CI, 1.03-3.85; P = .04) showed weaker associations with PFS. Alterations in pre-CT ctDNA were independently associated with OS (HR, 4.46; 95% CI, 1.86-10.69; P = 7.97 × 10-4). The findings of this cohort study indicate that prognostic models incorporating ctDNA features are useful in ESCC. Both ctDNA level and NFE2L2 alterations pre-CT and before cycle III were found to be important prognostic factors in palliative groups, and ctDNA alterations after treatment and at 6 months after surgery may define high-risk groups for recurrence in the curative group. High-risk patients can benefit by a timely switch to the next therapeutic options.

Risk prediction of esophageal squamous cell carcinoma recurrence in patients who underwent esophagectomy after receiving neoadjuvant treatment: a nationwide retrospective study in Japan.

Although neoadjuvant treatment (NAT) has become the standard of care for patients with locally advanced esophageal cancer, the risk of recurrence remains high. The risk must be predicted accurately, so that appropriate adjuvant therapy can be planned. We aimed to develop a model predicting recurrence of esophageal squamous cell carcinoma (ESCC) in patients who received NAT before esophagectomy. This nationwide study included 3874 patients from 85 institutions. Patients who underwent NAT and then surgery for ESCC were eligible. We developed a Cox proportional hazards model and created a nomogram to predict disease recurrence after NAT and curative esophagectomy. Of the patients, 268 (6.9%), 1280 (33.0%), 2006 (51.8%), and 320 (8.3%) had clinical stage I, II, III, and IV tumors, respectively. The 5-year recurrence rate was 45.1% (95% confidence interval 43.4%-46.7%). Multivariable analysis revealed that body mass index, type of neoadjuvant treatment, primary tumor location, operative blood loss, pathological tumor stage, pathological therapeutic effect, and leakage were independently associated with disease recurrence. Using 13 commonly measured perioperative variables, we created a predictive nomogram, and the area under the curve was 0.783 (95% confidence interval 0.766-0.800). This nomogram was also adequately validated internally and had excellent calibration capacity (calibration slope, 0.992). The model developed in this study adequately predicted ESCC recurrence in patients who underwent NAT and then esophagectomy. Further research with this nomogram is needed to assess the effect of adjuvant therapy in patients at high risk for recurrence.

Study on the prognostic influencing factors of esophageal squamous cell carcinoma and the predictive value of inflammatory reaction indexes on its postoperative recurrence

Objective: To explore the influence factors of poor prognosis of esophageal squamous cell carcinoma (ESCC) and the predictive value of inflammatory reaction indexes including neutrophils and lymphocytes ratio (NLR), platelet and lymphocyte ratio (PLR), monocyte and lymphocyte ratio (MLR) provision and differentiation degree, infiltration depth, lymph node metastasis number on the postoperative recurrence of ESCC. Methods: A total of 130 patients with ESCC who underwent radical resection from February 2017 to February 2019 in Nanyang Central Hospital were selected and divided into good prognosis group (66 cases) and poor prognosis group (64 cases) according to the prognostic effect. The clinical data and follow-up data were collected. Multivariate logistic regression analysis was used to determine the independent influencing factors of poor prognosis. Spearman correlation analysis was used to determine the correlation between preoperative NLR, PLR and MLR with the degree of differentiation, depth of invasion and number of lymph node metastases. Receiver operating characteristic (ROC) curve analysis was used to evaluate the efficacy of NLR, PLR and MLR in predicting poor prognosis of ESCC. Results: Univariate analysis showed that the degree of differentiation, the degree of invasion and the number of lymph node metastasis were related to the prognoses of patients with ESCC (P<0.05). Multivariate logistic regression analysis showed that the degree of differentiation, depth of invasion and number of lymph node metastases were independent influencing factors for poor prognosis of patients with ESCC, moderate differentiation (OR=2.603, 95% CI: 1.009-6.715) or low differentiation (OR=9.909, 95% CI: 3.097-31.706), infiltrating into fibrous membrane (OR=14.331, 95% CI: 1.333-154.104) or surrounding tissue (OR=23.368, 95% CI: 1.466-372.578), the number of lymph node metastases ≥ 3 (OR=9.225, 95% CI: 1.693-50.263) indicated poor prognosis. Spearman correlation analysis showed that NLR was negatively correlated with the degree of differentiation and the number of lymph node metastases (r=-0.281, P=0.001; r=-0.257, P=0.003), PLR was negatively correlated with the degree of differentiation, depth of invasion and number of lymph node metastasis (r=-0.250, P=0.004; r=0.197, P=0.025; r=-0.194, P=0.027), MLR was positively correlated with the degree of differentiation and the number of lymph node metastasis (r=0.248, P=0.004; r=0.196, P=0.025). ROC curve analysis showed that the areas under the curve of NLR, PLR and MLR in predicting poor prognosis of ESCC were 0.971, 0.925 and 0.834, respectively. The best cut-off value of NLR was 2.87. The sensitivity and specificity of NLR in predicting poor prognosis of ESCC were 90.6% and 87.9%, respectively. The optimal cut-off value of PLR was 141.75. The sensitivity and specificity for predicting poor prognosis of ESCC were 92.2% and 87.9%, respectively. The best cut-off value of MLR was 0.40. The sensitivity and specificity of MLR in predicting poor prognosis of esophageal squamous cell carcinoma were 54.7% and 100.0%, respectively. Conclusions: The degree of differentiation, the degree of invasion and the number of lymph node metastases are closely related to the poor prognosis of patients with esophageal squamous cell carcinoma. NLR, PLR and MLR can provide important information for predicting the poor prognosis of esophageal squamous cell carcinoma.

SAMD9 Promotes Postoperative Recurrence of Esophageal Squamous Cell Carcinoma by Stimulating MYH9-Mediated GSK3β/β-Catenin Signaling.

Recurrence is a challenge to survival after the initial treatment of esophageal squamous cell carcinoma (ESCC). But, its mechanism remains elusive and there are currently no biomarkers to predict postoperative recurrence. Here, the possibility of sterile alpha motif domain-containing protein 9 (SAMD9) as a predictor of postoperative recurrence of ESCC is evaluated and the molecular mechanisms by which SAMD9 promotes ESCC recurrence are elucidated. The authors found that the high level of SAMD9 is correlated with postoperative recurrence and poor prognosis of ESCC. Overexpression of SAMD9 promotes tumor stemness, angiogenesis, and EMT, while downregulation of SAMD9 reduced these phenotypes. Mechanistically, it is found that SAMD9 stimulated ubiquitination-mediated glycogen synthase kinase-3 beta (GSK-3β) degradation by interaction with myosin-9 (MYH9) and TNF receptor-associated factor 6 (TRAF6), which in turn activated Wnt/β-catenin pathway. Further, the authors demonstrated that silencing SAMD9 inhibited lung metastasis and tumor formation in vivo. Finally, the authors found that silencing MYH9 or β-catenin, or overexpressing GSK-3β inhibited SAMD9-stimulated ESCC cell stemness, EMT, angiogenesis, metastasis, and tumorigenicity. Together, the findings indicate that the SAMD9/MYH9/GSK3β/β-catenin axis promotes ESCC postoperative recurrence and that SAMD9 is a crucial target for ESCC therapy. Additionally, SAMD9 has the potential as a predictor of postoperative recurrence in ESCC.

The usefulness of the total metabolic tumor volume for predicting the postoperative recurrence of thoracic esophageal squamous cell carcinoma

BackgroundInduction or adjuvant therapies are not always beneficial for thoracic esophageal squamous cell carcinoma (ESCC) patients, and it is thus important to identify patients at high risk for postoperative ESCC recurrence. We investigated the usefulness of the total metabolic tumor volume (TMTV) for predicting the postoperative recurrence of thoracic ESCC.MethodsWe retrospectively analyzed the cases of 163 thoracic ESCC patients (135 men, 28 women; median age of 66 [range 34–82] years) treated at our hospital in 2007–2012. The TMTV was calculated from the fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in the primary lesion and lymph node metastases. The optimal cut-off values for relapse and non-relapse were obtained by the time-dependent receiver operating curve analyses. Relapse-free survival (RFS) was evaluated by the Kaplan-Meier method, and between-subgroup differences in survival were analyzed by log-rank test. The prognostic significance of metabolic parameters and clinicopathological variables was assessed by a Cox proportional hazard regression analysis. The difference in the failure patterns after surgical resection was evaluated using the χ2-test.ResultsThe optimal cut-off value of TMTV for discriminating relapse from non-relapse was 3.82. The patients with a TMTV ≥3.82 showed significantly worse prognoses than those with low values (p < 0.001). The TMTV was significantly related to RFS (model 1 for preoperative risk factors: TMTV: hazard ratio [HR] =2.574, p = 0.004; model 2 for preoperative and postoperative risk factors: HR = 1.989, p = 0.044). The combination of the TMTV and cN0–1 or pN0–1 stage significantly stratified the patients into low-and high-risk recurrence groups (TMTV cN0–1, p < 0.001; TMTV pN0–1, p = 0.004). The rates of hematogenous and regional lymph node metastasis were significantly higher in the patients with TMTV ≥3.82 than those with low values (hematogenous metastasis, p < 0.001, regional lymph node metastasis, p = 0.011).ConclusionsThe TMTV was a more significantly independent prognostic factor for RFS than any other PET parameter in patients with resectable thoracic ESCC. The TMTV may be useful for the identifying thoracic ESCC patients at high risk for postoperative recurrence and for deciding the patient management.

Clinical impact of remnant lymphatic invasion on the recurrence of esophageal squamous cell carcinoma after esophagectomy with neoadjuvant chemotherapy.

For stage II and III esophageal squamous cell carcinoma (ESCC), neoadjuvant chemotherapy (NAC) followed by esophagectomy is recommended in the Japanese guidelines for the diagnosis and treatment of esophageal cancer. However, recurrence of ESCC is common regardless of the NAC regimen and surgical method, and NAC demonstrates limited efficacy against recurrence. Therefore, the present study was conducted to identify risk factors of recurrence of ESCC with surgery after NAC. The outcomes of 51 patients who underwent esophagectomy for ESCC after NAC from 2010 to 2017 at Kyushu University Hospital were retrospectively analyzed. A total of 52 patients with ESCC without NAC followed by esophagectomy from 2001 to 2017 were selected for comparison. Among patients who underwent NAC followed by surgery, only lymphatic invasion (LY; hazard ratio, 2.761; 95% CI, 1.86-6.43, P=0.018) was an independent factor significantly associated with 3-year recurrence-free survival in the multivariate analysis. In patients with pathologic lymph node metastasis (pN) and no LY after NAC, there was significantly less recurrence compared with patients with pN and LY (P=0.0085), whereas in patients without LY after NAC, the presence of pN was not significantly associated with recurrence (P=0.2401). There were significantly fewer LY (+) patients in the NAC (+) group (P=0.0158) compared with those in the NAC (−) group. The presence of LY was an independent risk factor for recurrence of ESCC after esophagectomy following NAC. Overall, adjuvant treatment after surgery may be required in cases with remnant LY after NAC.

Efficacy and safety of re-irradiation for locoregional esophageal squamous cell carcinoma recurrence after radiotherapy: a systematic review and meta-analysis

BackgroundThere is currently no standard treatment for locoregional recurrence of esophageal squamous cell carcinoma (ESCC) previously treated with radiotherapy. This study aimed to assess the efficacy and safety of re-irradiation for ESCC patients with locoregional recurrence.MethodsThe PubMed, EmBase, and Cochrane library databases were systematically searched for eligible studies published before January 2021. The pooled effect estimates were calculated using the random effects model. Subgroup analyses were conducted to assess the treatment effectiveness of re-irradiation based on specific characteristics.ResultsNine retrospective studies including 573 ESCC patients with locoregional recurrence were selected. The pooled incidences of the 1-year, 2-year, 3-year, and 5-year survival for patients after re-irradiation were 59% (95% confidence interval [CI]: 35–83; P < 0.001), 25% (95% CI: 16–33; P < 0.001), 25% (95% CI: 4–45; P = 0.017), and 15% (95% CI: 2–27; P = 0.024), respectively. The rates of complete response and local re-recurrence after re-irradiation were 54% (95% CI: 21–88; P = 0.001) and 62% (95% CI: 55–70; P < 0.001), respectively. The median overall survival and local failure-free survival for patients after re-irradiation were 13.94 months (95% CI: 4.18–46.51; P < 0.001) and 11.01 months (95% CI: 5.99–20.22; P < 0.001), respectively. Grade ≥ 3 adverse events of esophageal perforation, tracheoesophageal fistula, and radiation pneumonitis were significantly more common after re-irradiation.ConclusionsThis study found that re-irradiation for ESCC patients with locoregional recurrence after previous radiotherapy was feasible. However, patients should be carefully observed in order to treat associated adverse events, including esophageal perforation, tracheoesophageal fistula, and radiation pneumonitis.

GTF2E2 is a novel biomarker for recurrence after surgery and promotes progression of esophageal squamous cell carcinoma via miR-139-5p/GTF2E2/FUS axis

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal gastrointestinal malignancies with high mortality. Recurrence develops within only a few years after curative resection and perioperative adjuvant therapy in 30–50% of these patients. Therefore, it is essential to identify postoperative recurrence biomarkers to facilitate selecting the following surveillance and therapeutic strategies. The general transcription factor IIE subunit beta (GTF2E2) is crucial for physiological and pathological functions, but its roles in the aggression and recurrence of ESCC remain ambiguous. In this study, we found that GTF2E2 was highly expressed in ESCC samples, and elevated GTF2E2 expression predicted early recurrence after surgery for ESCC patients. High expression of GTF2E2 associated with more aggressive clinic features and poor prognosis. GTF2E2 promoted the proliferation and mobility of ESCC cells in vitro and in vivo. We further revealed that miR-139-5p repressed GTF2E2 expression by downregulating its mRNA through binding with Argonaute 2 (Ago2). Rescue assays suggested that miR-139-5p affected GTF2E2-mediated ESCC progression. Moreover, GTF2E2 positively interacted with FUS promoter and regulated FUS expression, and the phenotype changes caused by GTF2E2 manipulation were recovered by rescuing FUS expression in ESCC cells. Additionally, we demonstrated that GTF2E2 promotes ESCC cells progression via activation of the AKT/ERK/mTOR pathway. In conclusion, GTF2E2 may serve as a novel biomarker for recurrence after surgery and a potential therapeutic target for ESCC patients, and it promotes ESCC progression via miR-139-5p/GTF2E2/FUS axis.

Postoperative follow-up strategy based on event dynamics for esophageal squamous cell carcinoma.

BackgroundDespite the improvements in radical surgery for esophageal squamous cell carcinoma (ESCC), a large number of patients still develop recurrence. This research sought to graphically depict patterns in ESCC recurrence following curative surgical treatment using event dynamics and clarify approaches to postsurgical follow-up on the basis of recurrence time.MethodsThis study included 717 individuals with ESCC who received radical surgery in the Thoracic Department at Fujian Medical University Union Hospital between 2013 and 2016. Event dynamics analysis was performed on the basis of hazard rates. An initial event was defined as the occurrence of local recurrence, distant metastasis, or both.ResultsAfter complete resection, patients were followed up for a median of 44 months (range, 2–83 months). A total of 223 (31.1%) patients developed recurrence, including 122 (17.0%) patients who developed only locoregional recurrence, and 101 (14.1%) patients who developed only distant metastasis or both locoregional recurrence and distant metastasis. Recurrences were concentrated mainly (98.2%) in the first 4 years of follow-up among all recurrences, with 100 cases (44.8%) in the first year, 69 cases (30.9%) in the second year, and 50 cases (22.4%) in the third and fourth years.ConclusionsAfter curative surgery in a multimodal setting, a significant number of patients still experienced recurrence within 4 years after surgery, which suggests that current postoperative esophageal cancer follow-up strategies may need to be modified.

Metabolomic analysis of exosomal-markers in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a worldwide malignancy with high mortality rates and poor prognosis due to the lack of effective biomarkers for early detection. Exosomes have been extensively explored as attractive biomarkers for cancer diagnosis and treatment. However, little is known about exosome metabolomics and their roles in ESCC. Here, we performed a targeted metabolomic analysis of plasma exosomes and identified 196 metabolites, mainly including lipid fatty acids, benzene, amino acids, organic acids, carbohydrates and fatty acyls. We systematically compared metabolome patterns of exosomes via machine learning from patients with recrudescence and patients without recrudescence and demonstrated a marker set consisting of 3'-UMP, palmitoleic acid, palmitaldehyde, and isobutyl decanoate for predicting ESCC recurrence with an AUC of 98%. These metabolome signatures of exosomes retained a high absolute fold change value at all ESCC stages and were very likely associated with cancer metabolism, which could be potentially applied as novel biomarkers for diagnosis and prognosis of ESCC.

Clinical Application Value Of Prognostic Nutritional Index For Predicting Survival In Patients With Esophageal Squamous Cell Carcinoma Undergoing Radical Chemoradiotherapy Or Radiotherapy

The prognostic nutrition index (PNI) has been shown to have prognostic value in several common cancers. We explore its clinical application value in the prognosis of patients with esophageal squamous cell carcinoma (ESCC) undergoing radical chemoradiotherapy (CRT) or radiotherapy (RT). Overall, 193 patients with ESCC who received radiotherapy with or without chemotherapy at Sichuan Cancer Hospital from March 20, 2012 to December 25, 2017 were retrospectively analyzed. Based on serum measurements before treatment, PNI at ESCC recurrence was calculated as albumin (g/L) + 5 × total lymphocyte count. Kaplan-Meier method and Cox proportional regression model were used to analyze the relationship between PNI and overall survival. The PNI of 193 ESCC patients was 49.01 ± 4.68. The optimal cutoff value of PNI was calculated to be 47.975, and the patients were divided into a low PNI group (<47.975) and a high PNI group (≥47.975). PNI is related to tumor length, T-stage, and Synchronous chemotherapy in ESCC patients (P <0.05). The median OS for the entire group was 22.37 months. The median OS of patients in the high PNI group (PNI ≥ 47.975) and low PNI group (PNI <47.975) were 32.63 months and 15.4 months, respectively, and the 3-year survival rates were 47.5% and 32.2%, and 5-year survival rates were 37.7% and 16.8%, respectively, and the differences were statistically significant (P = 0.001). Univariate analysis showed that PNI, tumor length, T stage and Synchronous chemotherapy were related to the prognosis of ESCC patients (P <0.05). Multivariate analysis showed that tumor length (P = 0.019), synchronous chemotherapy (P = 0.009), and PNI (P = 0.003) were independent prognostic factors affecting the prognosis of patients in ESCC treated with RT or CRT. The calculation of PNI value is simple, reliable and repeatable, which can improve the accuracy of patients' prognosis. And it needs to be further confirmed by the prospective study of large sample size.

Clinical Application Value of the Prognostic Nutritional Index for Predicting Survival in Patients with Esophageal Squamous Cell Carcinoma Undergoing Chemoradiotherapy or Radiotherapy

Background The prognostic nutrition index (PNI) has been shown to have prognostic value for several common cancers. The study aim was to explore the clinical application value of the PNI for prognosis of patients with esophageal squamous cell carcinoma (ESCC) treated with radical chemoradiotherapy (CRT) or radiotherapy (RT). Methods Overall, 193 patients with ESCC who received radiotherapy with or without chemotherapy at Sichuan Cancer Hospital from March 20, 2012 to December 25, 2017 were retrospectively analyzed. Based on serum measurements before treatment, the PNI at ESCC recurrence was calculated as albumin (g/L) + 5 × total lymphocyte count. The Kaplan–Meier method and Cox proportional regression model were used to analyze the relationship between PNI and overall survival (OS). Results The average PNI of 193 ESCC patients was 49.01 ± 4.68. The optimal cutoff value of PNI was 47.975, and the patients were divided into a low-PNI group (<47.975) and a high-PNI group (≥47.975). PNI was related to tumor length, T-stage and synchronous chemotherapy in ESCC patients (P < 0.05). The median OS for the entire group was 22.37 mo,. The median OS of patients in the high-PNI group and low-PNI group were 32.63 mo, and 15.4 mo, respectively, the 3-year survival rates were 47.5% and 32.2% and the 5-year survival rates were 37.7% and 16.8%, respectively, (all P = 0.001). Univariate analysis showed that PNI, tumor length, T-stage and synchronous chemotherapy were related to the prognosis of ESCC patients (P < 0.05). Multivariate analysis showed that tumor length (P = 0.019), synchronous chemotherapy (P = 0.009) and PNI (P = 0.003) were independent prognostic factors affecting the prognosis of patients in ESCC treated with RT or CRT. Conclusions The calculation of PNI value is simple, reliable and repeatable and can improve the accuracy of a patient’s prognosis. Confirmation of these results by a large-sample prospective study is desirable.

Newly developed primary malignancies in long-term survivors who underwent curative esophagectomy for squamous cell carcinoma of the esophagus.

We evaluated the efficacy of the long-term follow-up of patients who underwent radical esophagectomy for esophageal squamous cell carcinoma (ESCC) to screen for recurrence and new primary malignancies. We retrospectively collected 448 ESCC patients who underwent radical esophagectomy. Esophagogastroduodenoscopy, computed tomography, a stool test and the assessment of the serum concentration of squamous cell carcinoma antigen and carcinoembryonic antigen were performed annually, even over 5 years after esophagectomy. The incidence of ESCC recurrence and new primary malignancies was investigated. We enrolled 222 patients who survived at least 5years after esophagectomy. A total of 104 new primary malignancies occurred in 82 patients (36.9%) after esophagectomy. Twenty-one malignancies were in the head and neck region, 14 in the residual esophagus, 13 in the prostate and 11 in the gastric tube and lung. Patients who developed new primary malignancies after esophagectomy had a significantly higher Brinkman index than those without new malignancies. An endoscopic approach successfully treated 92.9% of carcinomas in the residual esophagus, 90.9% of cancers in the gastric tube and 42.9% of carcinomas in the head and neck region. The incidence of new primary malignancies was higher than the age-standardized incidence. Long-term follow-up and systemic screening may increase the probability of an early diagnosis and subsequent low-invasive treatment.

Controlling lymph node micrometastases by neoadjuvant chemotherapy affects the prognosis in advanced esophageal squamous cell carcinoma.

The purpose of this study is to determine the clinical significance of micrometastases after neoadjuvant chemotherapy (NAC) and the difference in controlling micrometastases using different NAC regimens in resectable advanced esophageal squamous cell carcinoma (ESCC). We analyzed patients with ESCC who underwent esophagectomy with lymph node dissection after NAC with Adriamycin + cisplatin + 5-fluorouracil (ACF) or docetaxel + cisplatin + 5-fluorouracil (DCF). Micrometastasis was defined as a single isolated cancer cell or cluster of cancer cells on the cervical, recurrent nerve, or abdominal LNs as shown by immunohistochemical staining with anti-cytokeratin antibody (AE1/AE3). The associations between micrometastases, recurrence, prognosis, and regimen differences were investigated. One hundred and one cases (ACF group: 51 cases; DCF group: 50 cases) were analyzed. Micrometastases occurred in 24 patients (23.8%): 17/51 (33.3%) in the ACF group and 7/50 (13.5%) in the DCF group (p = 0.0403). The 5-year recurrence-free survival (RFS) rates for patients without (n = 77) and with (n = 24) micrometastases were 62 and 32%, respectively, (hazard ratio, 2.158; 95% confidence interval, 1.170-3.980; stratified log-rank test, p = 0.0115). A multivariate analysis showed that stage pN1 or higher and micrometastases were significant risk factors affecting RFS. In resectable advanced ESCC, controlling micrometastases in the LNs after NAC varied by regimen and may be associated with preventing ESCC recurrence.

Clinical application value of prognostic nutritional index for predicting survival in patients with esophageal squamous cell carcinoma undergoing chemoradiotherapy (CRT) or radiotherapy.

e24075 Background: The prognostic nutrition index (PNI) has been shown to have prognostic value in several common cancers. We explore its clinical application value in the prognosis of patients with esophageal squamous cell carcinoma (ESCC) undergoing radical chemoradiotherapy (CRT) or radiotherapy. Methods: Overall, 193 patients with ESCC who received radiotherapy with or without chemotherapy at Sichuan Cancer Hospital from March 20, 2012 to December 25, 2017 were retrospectively analyzed. Based on serum measurements before treatment, PNI at ESCC recurrence was calculated as albumin (g/L) + 5 × total lymphocyte count. Kaplan-Meier method and Cox proportional regression model were used to analyze the relationship between PNI and overall survival (OS). Results: The PNI of 193 ESCC patients was 49.01 ± 4.68. The optimal cutoff value of PNI was calculated to be 47.975. The patients were divided into a low PNI group (&lt;47.975) and a high PNI group (≥47.975). The median OS for the entire group was 22.37 months. The median OS of patients in the high PNI group (PNI ≥ 47.975) and low PNI group (PNI &lt;47.975) were 32.63 months and 15.4 months, respectively. The 3-year overall survival rates were 47.5% and 32.2%, and 5-year overall survival rates were 37.7% and 16.8%, respectively, and the differences were statistically significant (P = 0.001). Multivariate analysis showed that tumor length (P = 0.019), synchronous chemotherapy (P = 0.009), and PNI (P = 0.003) were independent prognostic factors affecting the prognosis of patients in ESCC treated with radical CRT or radiotherapy. Conclusions: The calculation of PNI value is simple, reliable and repeatable, which can improve the accuracy of patients' prognosis. And it needs to be further confirmed by the prospective study of large sample size. Keywords: Esophageal squamous cell carcinoma, chemoradiotherapy, prognostic nutritional index, prognosis.

Predictions of Pathological Features and Recurrence Based on FDG-PET Findings of Esophageal Squamous Cell Carcinoma after Trimodal Therapy.

The degree of metabolic activity in tumor cells can be determined by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). Associations between FDG uptake by primary tumors of locally advanced esophageal squamous cell carcinoma (ESCC) under trimodal therapy and the pathological features of such tumors have not been fully investigated. We evaluated relationships between the maximal standardized uptake (SUVmax) in primary tumors on preoperative PET images and pathological features as well as cancer recurrence in 143 patients with ESCC who underwent neoadjuvant chemoradiotherapy (NCRT) followed by surgery. The post-SUVmax significantly differed after NCRT for ypT and ypN status, lymphatic invasion (LI), venous invasion (VI), and recurrence. Furthermore, the %ΔSUVmax (rate of decrease between before and after NCRT) for LI, VI, and recurrence significantly differed. Univariate and multivariate analyses selected post-SUVmax and %ΔSUVmax as independent preoperative predictors of recurrence-free survival [hazard ratio (HR) 1.46; 95% confidence interval (CI) 1.24-1.72 and HR 0.97; 95% CI 0.96-0.99, respectively; p < 0.001 for both]. Recurrence-free and overall survival were significantly stratified according to optimal SUVmax cutoffs for predicting recurrence (post- and %ΔSUVmax: 2.8 and 70, respectively). The post- and %ΔSUVmax of primary tumors were significantly associated with the pathological features and recurrence of ESCC under trimodal therapy. Therefore, FDG-PET can preoperatively predict the degree of aggressive tumor behavior in ESCC under trimodal therapy.