Node-positive Esophageal Squamous Cell Carcinoma Research Articles

The efficacy and safety of neoadjuvant sintilimab combined with chemotherapy in resectable locally advanced lymph node-positive esophageal squamous cell carcinoma: A real world study.

e16091 Background: Many phase III clinical trials (Keynote 590, Orient 15, etc) have all proved the role of immunotherapy combined with chemotherapy in the treatment of esophageal squamous cell carcinoma. This study was designed to evaluate the efficacy and safety of immunotherapy and chemotherapy as neoadjuvant therapy for resectable locally advanced lymph node-positive esophageal squamous cell carcinoma. Methods: This is a multicenter, 2-cohort (IO+CT group & CRT group), real world study. In IO+CT group, patients(pts) will receive sintilimab 200 mg once on day 1, albumin-bound paclitaxel 260g/m2 from day 1 to 4, carboplatin 80mg/m2 on day 1, every 21 days(Q3W) for 2 cycles. Key eligibility criteria included resectable, locally advanced lymph node-positive esophageal squamous cell carcinoma conformed by histology, and aged ≥18 years old with ECOG PS 0-1. The primary endpoint was pathologic complete response (pCR) rate. The secondary endpoints were event free survival (EFS), objective response rate (ORR), overall survival (OS) and safety. Results: From 7/2022 to 9/2023, 30 pts were enrolled in IO+CT group. In IO+CT group, among 30 pts who underwent surgery, 9 (30%) achieved pCR. 93.3% pts (28/30) achieved R0 resection. In 20 evaluable pts, 3(15%) achieved complete response (CR), 15(75%) achieved partial response (PR), 2(10%) achieved stable disease (SD). ORR and DCR were 90.0% (18/20) and 100.0% (20/20), respectively. There were no grade ≥2 treatment-related adverse events (TRAEs) appeared. The most common grade 1 TRAEs was fatigue (13.3%). Conclusions: In the real world, sintilimab plus chemotherapy used as neoadjuvant therapy in resectable locally advanced lymph node-positive esophageal squamous cell carcinoma could be effective and manageable toxicity. Clinical trial information: ChiCTR2200058565.

A Radiotherapy Dose Map-Guided Deep Learning Method for Predicting Pathological Complete Response in Esophageal Cancer Patients after Neoadjuvant Chemoradiotherapy Followed by Surgery.

Esophageal cancer is a deadly disease, and neoadjuvant chemoradiotherapy can improve patient survival, particularly for patients achieving a pathological complete response (ypCR). However, existing imaging methods struggle to accurately predict ypCR. This study explores computer-aided detection methods, considering both imaging data and radiotherapy dose variations to enhance prediction accuracy. It involved patients with node-positive esophageal squamous cell carcinoma undergoing neoadjuvant chemoradiotherapy and surgery, with data collected from 2014 to 2017, randomly split into five subsets for 5-fold cross-validation. The algorithm DCRNet, an advanced version of OCRNet, integrates RT dose distribution into dose contextual representations (DCR), combining dose and pixel representation with ten soft regions. Among the 80 enrolled patients (mean age 55.68 years, primarily male, with stage III disease and middle-part lesions), the ypCR rate was 28.75%, showing no significant demographic or disease differences between the ypCR and non-ypCR groups. Among the three summarization methods, the maximum value across the CTV method produced the best results with an AUC of 0.928. The HRNetV2p model with DCR performed the best among the four backbone models tested, with an AUC of 0.928 (95% CI, 0.884-0.972) based on 5-fold cross-validation, showing significant improvement compared to other models. This underscores DCR-equipped models' superior AUC outcomes. The study highlights the potential of dose-guided deep learning in ypCR prediction, necessitating larger, multicenter studies to validate the results.

A case of lymph node-positive esophageal squamous cell carcinoma with spontaneous regression of the primary lesion

A case of lymph node-positive esophageal squamous cell carcinoma with spontaneous regression of the primary lesion

Lymphatic invasion is a prognostic factor of pathological N0 esophageal squamous cell carcinoma.

Adjuvant treatment after upfront esophagectomy for esophageal squamous cell carcinoma (ESCC) is indicated only for patients with lymph node metastasis in Japan. However, the recurrence rate after curative resection is high even for node-negative patients; thus, understanding the prognostic factors for patients with node-negative ESCC, which still remains unidentified, is important. Here, we aimed to reveal the prognostic factors for the long-term outcomes of patients with node-negative ESCC. Moreover, we compared the long-term outcomes among high-risk node-negative and node-positive patients. This single-institution retrospective study included 103 patients with pT1b-3N0 ESCC who underwent upfront surgery to identify the population at a high risk of recurrence. To compare overall survival (OS) and recurrence-free survival (RFS) between high-risk node-negative and node-positive patients, 51 node-positive ESCC patients with pStage IIIA or less who had undergone upfront surgery were also included. Univariable and multivariable analyses were performed using the Cox proportional hazard regression model. OS and RFS were compared using the log-rank test. Only lymphatic invasion (Ly+) was associated with worse 3-year OS (hazard ratio, 8.63; 95% confidence interval, 2.09-35.69; P = 0.0029) and RFS (hazard ratio, 4.87; 95% confidence interval, 1.69-14.02; P = 0.0034). The node-negative and Ly+ patients showed significantly worse OS (P = 0.0242) and RFS (P = 0.0114) than the node-positive patients who underwent chemotherapy. Ly+ is the only independent prognostic factor in patients with node-negative ESCC. Patients with node-negative and Ly+ ESCC may benefit from adjuvant treatment.

Postoperative adjuvant chemotherapy versus chemoradiotherapy for node-positive esophageal squamous cell carcinoma: a propensity score-matched analysis

Background and purposeAfter esophagectomy, adjuvant chemotherapy (S + CT) and adjuvant chemoradiotherapy (S + CRT) can improve survival in patients with node-positive resectable esophageal cancer. However, we are not aware of any studies that directly compared these adjuvant treatments. This study aimed to compare S + CT and S + CRT for patients with esophageal cancer.Materials and methodsWe retrospectively identified patients with node-positive esophageal squamous cell carcinoma who underwent S + CT or S + CRT at Sichuan Cancer Hospital during 2008–2017. The patients’ characteristics were compared, as well as their overall survival (OS) and disease-free survival (DFS) outcomes. Propensity score matching was used to create balanced patient groups according to adjuvant treatment, and a Cox proportional hazards model was used to identify factors that predicted the survival outcomes.ResultsThe 859 eligible patients underwent S + CRT (250 patients, 29.1%) or S + CT (609 patients, 70.9%). After propensity score matching (247 patients per group), the 5-year OS rates were 41.8% for S + CRT and 26.8% for S + CT (p = 0.028), and the 5-year DFS rates were 37.2% for S + CRT and 25.5% for S + CT (p = 0.012). Multivariate Cox regression analysis of the matched samples revealed that, relative to the S + CT group, the S + CRT group had better OS (hazard ratio: 0.71, 95% CI: 0.56–0.91; p = 0.006) and DFS (hazard ratio: 0.70, 95% CI: 0.56–0.88; p = 0.002).ConclusionAmong patients with node-positive resectable esophageal squamous cell carcinoma, S + CRT was associated with better OS than S + CT. A multicenter randomized clinical trial is warranted to confirm these findings.

Prognostic Value of Lymph Node-To-Primary Tumor Standardized Uptake Value Ratio in Esophageal Squamous Cell Carcinoma Treated with Definitive Chemoradiotherapy.

We aimed to investigate the prognostic value of the relative maximum standardized uptake value (SUV) of metastatic lymph node (LN) compared with that of primary tumor (SUVLN/SUVTumor) based on a pretreatment [18F]-FDG PET/CT scan in patients with clinically node-positive esophageal squamous cell carcinoma (cN+ ESCC) treated with definitive chemoradiotherapy (dCRT). We retrospectively evaluated cN+ ESCC patients who underwent a PET/CT scan before dCRT. Time-dependent receiver operating characteristics analysis was performed to identify the optimal cutoff value for SUVLN/SUVTumor. Prognostic influences of SUVLN/SUVTumor on distant metastasis-free survival (DMFS) and overall survival (OS) were evaluated using the Kaplan–Meier method and log-rank test for univariate analysis and Cox’s proportional hazards regression model for multivariate analysis. We identified 112 patients with newly diagnosed cN+ ESCC. After a median follow-up of 32.0 months, 50 (44.6%) patients had distant failure and 84 (75.0%) patients died. Patients with high SUVLN/SUVTumor (≥ 0.39) experienced worse outcomes than low SUVLN/SUVTumor (< 0.39) (two-year DMFS: 26% vs. 70%, p < 0.001; two-year OS: 21% vs. 48%, p = 0.001). Multivariate analysis showed that SUVLN/SUVTumor was an independent prognostic factor for both DMFS (adjusted HR 2.24, 95% CI 1.34–3.75, p = 0.002) and OS (adjusted HR 1.61, 95% CI 1.03–2.53, p = 0.037). Pretreatment of SUVLN/SUVTumor is a simple and useful marker for prognosticating DMFS and OS in cN+ ESCC patients treated with dCRT, which may help in tailoring treatment and designing future clinical trials.

Neoadjuvant versus definitive chemoradiation in patients with squamous cell carcinoma of the esophagus

BackgroundMultimodal treatment with neoadjuvant chemoradiation followed by surgery (nCRT + S) is the treatment of choice for patients with locally advanced or node-positive esophageal squamous cell carcinoma (E-SCC). Those who are unsuitable or who decline surgery can be treated with definitive chemoradiation (dCRT). This study compares the oncologic outcome of nCRT + S and dCRT in E-SCC patients.MethodsBetween 2011 and 2017, 95 patients with E-SCC were scheduled for dCRT or nCRT+ S with IMRT at our department. Patients undergoing dCRT received at least 50 Gy and those undergoing nCRT + S received at least 41.4 Gy. All patients received simultaneous chemotherapy with either carboplatin and paclitaxel or cisplatin and 5-fluoruracil. We retrospectively compared baseline characteristics and oncologic outcome including overall survival (OS), progression-free survival (PFS) and site of failure between both treatment groups.ResultsPatients undergoing dCRT were less likely to have clinically suspected lymph node metastases (85% vs. 100%, p = 0.019) than patients undergoing nCRT + S and had more proximally located tumors (median distance from dental arch to cranial tumor border 20 cm vs. 26 cm, p < 0.001). After a median follow up of 25.6 months for surviving patients, no significant differences for OS and PFS were noticed comparing nCRT + S and dCRT. However, the rate of local tumor recurrence was significantly higher in patients treated with dCRT than in those treated with nCRT + S (38% vs. 10%, p = 0.002). Within a multivariate Cox regression model, age, tumor location, and tumor grading were the only independent parameters affecting OS and PFS. In addition to that, proximal tumor location was the only parameter independently associated with an increased risk for local treatment failure.ConclusionIn E-SCC patients treated with either dCRT or nCRT + S, a higher rate of local tumor recurrence was seen in patients treated with dCRT than in patients treated with nCRT + S. There was at least a trend towards an improved OS and PFS in patients undergoing nCRT + S. However, this should be interpreted with caution, because proximal tumor location was the only parameter independently affecting the risk of local tumor recurrence.

Favorable versus unfavorable prognostic groups by post-chemoradiation FDG-PET imaging in node-positive esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy.

Our purpose was to examine the prognostic value of post-CRT PET based on the presence or absence of FDG-avid metastatic lymph node(s) and metabolic response of the primary tumor in patients with clinically node-positive ESCC treated with definitive chemoradiotherapy (dCRT). We identified 108 eligible patients treated by chemoradiotherapy (CRT) with or without resection from our prospectively collected database. Absence of FDG-avid metastatic lymph node with at least partial response of the primary tumor on PET scan after initial CRT was defined as the Post-CRT PET favorable group (yPET-F), and otherwise as unfavorable group (yPET-U). The Kaplan-Meier method and Cox regression were performed for survival analyses and multivariable analysis, respectively. The study cohort was comprised of 59 patients receiving dCRT. Forty-five patients receiving trimodality therapy (TMT) comprised the comparative group and four patients were excluded from further analyses for developing interval distant metastasis detected on post-CRT PET scan. The median follow-up for the study cohort was 41months. On K-M analysis of the study cohort, yPET-F was found to have significantly better OS (2-year: 72.5% vs 13.7%, p < 0.01) and DMFS (2-year: 71.6% vs 36.6%, p = 0.01) than yPET-U. In multivariable analysis, yPET-F remained as a strong independent favorable prognosticator on both OS (HR 0.08, p < 0.01) and DMFS (HR 0.14, p = 0.02) for the dCRT cohort. Compared with TMT cohort, for yPET-U patients, TMT had better OS (p = 0.03) than dCRT-Operable and dCRT-Operable had superior OS (p = 0.04) than dCRT-Unresectable. For yPET-F patients, there was no difference in both OS (p > 0.99) and DMFS (p = 0.92) between these three groups. Absence of FDG-avid metastatic lymph node with at least partial response of the primary tumor on PET scan after CRT (i.e., yPET-F status) prognosticate for excellent OS and DMFS in cN+ ESCC patients treated with dCRT, and might be comparable to TMT.

Adjuvant chemotherapy with paclitaxel and cisplatin in lymph node-positive thoracic esophageal squamous cell carcinoma.

ObjectiveNo standard postoperative adjuvant chemotherapy has ever been established in node-positive esophageal squamous cell carcinoma (ESCC). This is a study to explore the effect of postoperative paclitaxel (PTX) and cisplatin (DDP) in lymph node-positive, completely resected thoracic ESCC patients.MethodsWe conducted a prospective phase II trial. Patients had pathologically node-positive thoracic ESCC with negative margins. Outcomes of disease-free survival (DFS) and overall survival (OS) were compared with a matched historical control cohort. The postoperative chemotherapy regimen consisted of 4 to 6 cycles of PTX 150 mg/m2 administered intravenously on d 1 followed by DDP 50 mg/m2 on d 2 every 14 d. ResultsForty-three patients were accrued from December 2007 to May 2012 at Cancer Hospital of Chinese Academy of Medical Sciences for adjuvant chemotherapy. The historical control group consisted of 80 patients who received complete resection but no adjuvant chemotherapy during the same period of time. Of the 43 patients with adjuvant chemotherapy, 37 (86.0%) patients completed 4 to 6 cycles of chemotherapy. The 3-year DFS rates were 56.3% in the adjuvant group and 34.6% in the control group (P=0.006). The 3-year OS rates were 55.0% in the adjuvant group and 37.5% in the control group (P=0.013). Multivariate analysis revealed that postoperative chemotherapy was the significant predictor for improved OS (P=0.005).ConclusionsBiweekly adjuvant PTX and DDP might improve 3-year DFS and OS in lymph node-positive, curatively resected thoracic ESCC patients. These conclusions warrant further study in randomized phase III clinical trials.

643P - A randomized phase II study of leucovorin, 5-fluorouracil with or without oxaliplatin (LV5FU2 vs. FOLFOX) for curatively-resected, node-positive esophageal squamous cell carcinoma

643P - A randomized phase II study of leucovorin, 5-fluorouracil with or without oxaliplatin (LV5FU2 vs. FOLFOX) for curatively-resected, node-positive esophageal squamous cell carcinoma

Phase I Study of Postoperative Chemoradiation in Patients With Node-positive Esophageal Squamous Cell Carcinoma

Phase I Study of Postoperative Chemoradiation in Patients With Node-positive Esophageal Squamous Cell Carcinoma

Survival Benefits of Postoperative Chemoradiation for Lymph Node–Positive Esophageal Squamous Cell Carcinoma

Little is known about the efficacy of chemoradiation therapy after surgery for patients with esophageal squamous cell carcinoma. This retrospective study aimed to determine whether postoperative chemoradiation improves survival compared with surgery alone. Of 290 patients with esophageal squamous cell carcinoma, 104 received postoperative chemoradiation therapy (CRT group) and 186 underwent surgery alone (S group). Propensity score matching analysis was used to identify 56 well-balanced pairs of patients to compare outcomes. For N0 patients, overall survival (OS) and disease-free survival (DFS) were similar in both groups. For N+ patients, the median OS (31.0 versus 16.0 months) and the 3-year OS rate (45.8% versus 14.1%) were significantly higher in the CRT group than in the S group (p<0.001). Similarly, the median DFS (16.0 versus 9.0 months) and the 3-year DFS rate (24.1% versus 11.5%) were significantly higher in the CRT group than in the S group (p=0.002). In propensity-matched patients, a survival benefit was observed for N+ patients receiving postoperative chemoradiation (CRT versus S group: median OS 29.0 versus 16.0 months, 3-year OS rate 48.6% versus 16.8%; p=0.003). Disease-free survival (median DFS 11.0 versus 8.0 months, 3-year DFS rate 21.3% versus 12.5%) tended to be better in the CRT group than in the S group (p=0.057). Postoperative chemoradiation therapy provided a survival benefit for patients with lymph node-positive esophageal squamous cell carcinoma.

Abstract 1155: Serum microRNA-21 is a novel biomarker in patients with esophageal squamous cell carcinoma

Abstract Backgrounds and objective: Esophageal squamous cell carcinoma (ESCC) is one of the most difficult malignancies to be cured among gastrointestinal tract cancers. Recently, it was revealed that microRNAs stably exist in serum and may affect pathogenesis of several diseases. However, there are only a few reports that have demonstrated the significance of microRNA (mir) in the serum of patients with ESCC. Accordingly, the aims of this study were to clarify the status of mir-21 in the serum of ESCC patients and to reveal the usefulness of this molecule as a biomarker. Patients and methods: Serum samples were obtained from 52 patients diagnosed with ESCC, as well as from 17 “control” patients diagnosed with gallstones, without active inflammation, in Kumamoto University Hospital from 2008 to 2010. Pre-treatment serum samples were collected during diagnostic studies. Thirty-two ESCC patients received induction chemotherapy using the Docetaxel/ cisplatin /5-Fluorouracil (DCF) regimen (60 mg/m2 Docetaxel on day 1; 350 mg/m2 5-Fluorouracil and 6 mg/m2 cisplatin on days 1-5; 2 courses) after being diagnosed with node-positive ESCC. Twenty-four pairs of serum samples before and after chemotherapy were collected. The expression of miR-21 was determined by qRT-PCR using TaqMan microRNA assay Kits® (Applied Biosystems, USA). Results: The results of qRT-PCR analysis indicated that the ESCC patients had significantly higher levels of serum miR-21 than the control patients (P = 0.007). The value of area under the receiver operating characteristic curve was 0.885 for microRNA-21. When the patients were divided into two groups according to tumor size (≥40mm vs. &amp;lt;40mm), we found that the patient group with the larger tumors exhibited significantly higher levels of miR-21 than the patients with small-sized tumors. We examined the expression levels of miR-21 in the paired (pre- and post-therapy) serum samples of 24 patients who were treated with chemotherapy. The miR-21 expression levels in the patients’ post-chemotherapy samples were significantly reduced compared to the corresponding levels in the pre-chemotherapy samples (P=0.009). When the patient response to cancer chemotherapy was evaluated by RECIST v. 1.0, we found a significant decrease in the miR-21 expression levels in the Complete Response /Partial Response patients, whereas no significant decrease occurred in the levels in Stable Disease/ Progressive Disease patients (P = 0.003 versus N.S). Conclusion:Serum microRNA-21 is considered to be a novel biomarker for diagnosing ESCC, and it can also be used as a response marker during chemotherapy for ESCC patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1155. doi:10.1158/1538-7445.AM2011-1155

Abstract 4056: MicroRNA-21 and −26a are novel markers to predict the sensitivity to chemotherapy in esophageal squamous cell carcinoma

Abstract Backgrounds : Esophageal squamous cell carcinoma (ESCC) is one of the most difficult malignancies to be cured among gastrointestinal tract cancers. Recently, the effect of neoadjuvant or induction chemotherapy followed by definitive local treatment for advanced ESCC has received much attention through some clinical trials. However, biomarkers which can predict the effect of chemotherapy have not yet been identified. MicroRNA (mir) is a recently discovered class of small non-coding RNAs that can regulate gene expression, and recent researches have demonstrated that changes in expression of some mirs might affect drug resistance. However, there are few reports which identified mirs related to drug resistance to ESCC, using pretreatment biopsy samples. Objective: In order to identify the mirs which can be biomarkers to predict chemosensitivity inESCC, correlation between the expression status of mirs in biopsy samples and the treatment effects has been investigated. Patients and methods: Forty patients with node-positive ESCC were eligible for this study from June 2008 to October 2009. Induction chemotherapy using Docetaxel/CDDP/5-FU (DCF) regimen (Docetaxel 60 mg/m2 on day1, 5-FU 350 mg/m2 and cisplatin 6 mg/m2 on day1-5) were given every 3 weeks for 2 courses. Tumor response to chemotherapy was evaluated by 18-F-fluorodeoxyglucose positron emission tomography(FDG-PET) before and after the chemotherapy, and decrease rate of standardized uptake value (SUV) of primary tumors during the chemotherapy has been calculated ((SUVpre - SUV post)/SUVpre X 100 (%)). When the decrease rate was more than%, the treatment was considered to be effective. Total RNA was isolated from formalin-fixed paraffin-embedded (FFPE) biopsy samples which were collected by upper gastrointestinal endoscopy. We analyzed the expression status of 28 mature mirs, which have been reported to be increased or decreased in ESCC samples or cell lines compared to normal epithelium, by Real-time quantitative RT-PCR. Results: At first, we have confirmed that expression status of mirs was preserved between FFPE biopsy samples and fresh snap tissues from patients who underwent surgery without any treatments. Among 40 patients treated with induction chemotherapy, there were 22 responders and 18 non-responders. Although 26 out of 28 mirs demonstrated similar expression profiles between responders and non-responders, mir-21and mir-26a were significantly overexpressed in FFPE biopsy samples from non-responders in compared with those from responders (P&amp;lt;0.05). Moreover, pathologic examination of surgically resected specimens revealed that expression of mir-21 and nir-26a was significantly correlated with histopathologic responsiveness. Conclusions: Expressions of mir-21 and mir-26a in the pretreatment biopsy specimens can be biomarkers to predict response to DCF in patients with ESCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4056.

Clinical benefit of chemosensitivity test for patients with regional lymph node-positive esophageal squamous cell carcinoma.

Patients who have undergone resection for lymph node-positive esophageal squamous cell carcinoma are at high risk of recurrence and early death. The role of the postoperative adjuvant chemotherapy in this population needs to be determined. The present study was designed to determine whether the chemosensitivity test in fresh human esophageal squamous cell carcinoma, using highly purified tumor cells, correlates with the clinical response. A retrospective review of all patients with resected squamous cell carcinoma of the thoracic esophagus between 1993 and 2000 was performed. We determined the chemosensitivity for cisplatin (CDDP), 5-fluorouracil (5-FU), mitomycin C, and adriamycin in vitro in fresh human esophageal squamous cell carcinoma using the MTT assay. Regional lymph node-positive (N1) patients who received sequential postoperative chemotherapy were compared with lymph node positive patients who underwent surgery alone. A total of 50 patients were reviewed, and chemosensitivity tests were successfully performed in 46 patients: 20 patients received surgery alone (S group), and 26 patients received surgery plus postoperative chemotherapy (SC group) according to results of MTT assay using highly purified tumor cells. When the SC group was divided into an SC-low group (inhibition rate of CDDP + 5-FU was below 85%, n = 15) and an SC-high group (over 85%, n = 11), the SC-high group showed more significant survival prolongation than the S group or the SC-low group (P < 0.01). Our results suggest that the results of the conventional MTT assay may be useful in evaluating the optimum adjuvant chemotherapy for patients with regional lymph node positive (pN1) esophageal squamous cell carcinoma.