Clinical outcomes of surgical resection for recurrent lesion after curative esophagectomy for esophageal squamous cell carcinoma: a nationwide, large-scale retrospective study

Background Several studies have reported the efficacy of resection for recurrent lesions. However, they involved a limited number of subjects. This study aimed to identify a subset of patients who benefit from surgical resection of recurrent lesions after curative esophagectomy for esophageal squamous cell carcinoma. Methods Clinicopathological features of 186 patients with esophageal squamous cell carcinoma who underwent surgical treatment for postoperative recurrent lesions at 37 accredited institutions of the Japanese Esophageal Society were evaluated. Results The most common recurrence site was the lymph node (106 cases; 58.6%), followed by the lung (40 cases; 22.1%). Univariate analyses revealed that pN 0–1 at esophagectomy (P = 0.0348), recurrence-free interval of ≥ 550 days (P = 0.0306), R0 resection (P < 0.0001), and absence of severe complications after resection for recurrent lesions (Clavien–Dindo grade < IIIa) (P = 0.0472) were associated with better overall survival after surgical resection. According to multivariate analyses, pN 0–1 (P = 0.0146), lung metastasis (P = 0.0274), recurrence-free interval after curative esophagectomy of ≥ 550 days (P = 0.0266), R0 resection (P = 0.0009), and absence of severe complications after resection for recurrent lesions (Clavien–Dindo grade < IIIa) (P = 0.0420) were independent predictive factors for better overall survival. Conclusions Surgical resection of recurrent esophageal squamous cell carcinoma lesions is a useful option, especially for cases involving lower pN stage, lung metastasis, long recurrence-free intervals after esophagectomy, and technically resectable lesions. Surgical risks should be minimized as much as possible.

321 RANDOM SURVIVAL FOREST FOR PERSONALISED PROGNOSTICATION AFTER ESOPHAGECTOMY

For patients with esophageal cancer, producing accurate prediction models for long-term survival after esophagectomy has proved challenging. We investigated whether Random Survival Forests (RSF), a machine learning method, could produce an accurate prognostic model for overall survival after esophagectomy. Methods The study used data from the 'National Oesophago-Gastric Cancer Audit' (NOGCA) and included patients diagnosed with esophageal adenocarcinoma or squamous cell carcinoma between 2012 and 2018 in England and Wales and who underwent a curative esophagectomy with adequate lymphadenectomy (15 lymph nodes) and survived to discharge (n = 6838). Missing data was handled using multiple imputation. 15 variables were selected for inclusion using Random Forest variable importance and used to train the final model. The same variables with non-linearity transformations were used to develop a traditional Cox regression model for comparison. Results Median survival was 50 months. The final RSF model had good discrimination on internal validation with a C-index of 0.7627 (0.7625–0.7629), exceeding the cox model 0.7539 (0.7541–0.7537). At 3 years post-surgery, overall survival was 56.2%. The RSF yielded a mean predicted survival of 59.3% (IQR 33.3–87.1%) with good calibration (Figure 1) compared to 57.4% (38.4%–79.8%) for the cox model. The most influential variables were lymph node involvement and pT/ypT stage, however other variables including neoadjuvant treatment completion and surgical complications were also important. Decision curve analysis was undertaken which also showed an increased net benefit with the RSF model. Conclusion A Random Forest survival model provided better performance in predicting survival after curative esophagectomy. This will allow more personalised predictions to be delivered clinicians and patients. An online web app is provided at https://uoscancer.shinyapps.io/NOGCA/

Risk Stratification of Cirrhotic Patients Undergoing Esophagectomy for Esophageal Cancer: A Single-Centre Experience

Concomitant liver cirrhosis is a crucial risk factor for major surgeries. However, only few data are available concerning cirrhotic patients requiring esophagectomy for malignant disease. From a prospectively maintained database of esophageal cancer patients, who underwent curative esophagectomy between 01/2012 and 01/2016, patients with concomitant liver cirrhosis (LCP) were compared to non-cirrhotic patients (NLCP).Of 170 patients, 14 cirrhotic patients with predominately low MELD scores (≤ 9, 64.3%) were identified. Perioperative outcome was significantly worse for LCP, as proofed by 30-day (57.1% vs. 7.7, p<0.001) and 90-day mortality (64.3% vs. 9.6%, p<0.001), anastomotic leakage rate (64.3 vs. 22.3%, p=0.002) and sepsis (57.1 vs. 21.5%, p=0.006). Even after adjustment for age, gender, comorbidities, and surgical approach, LCP revealed higher odds for 30-day and 90-day mortality compared to NLCP. Moreover, 5-year survival analysis showed a significantly poorer long-term outcome of LCP (p=0.023). For risk stratification, none of the common cirrhosis scores proved prognostic impact, whereas components as Bilirubin (auROC 94.4%), INR (auROC=90.0%), and preoperative ascites (p=0.038) correlated significantly with the perioperative outcome. Curative esophagectomy for cirrhotic patients is associated with a dismal prognosis and should be evaluated critically. While MELD and Child score failed to predict perioperative mortality, Bilirubin and INR proofed excellent prognostic capacity in this cohort.

Role of adjuvant therapy in esophageal cancer patients after neoadjuvant therapy and curative esophagectomy: A systematic review and meta-analysis.

e16083 Background: While neoadjuvant therapy followed by esophagectomy is the standard of care for locally advanced esophageal cancer, the role of adjuvant therapy is uncertain. As such, this review aims to analyze esophageal cancer patients who previously underwent neoadjuvant therapy followed by a curative resection (negative margins) to determine whether additional adjuvant therapy is associated with improved survival outcomes. Methods: MEDLINE, EMBASE, and CENTRAL databases were searched up to August 2020 for studies comparing patients with esophageal cancer who underwent neoadjuvant therapy and curative resection with and without adjuvant therapy. Primary outcome was overall survival (OS), and secondary outcomes were disease-free survival (DFS), locoregional recurrence, and distant recurrence at 1 and 5-years. Random effects meta-analysis was conducted where appropriate. Grading of recommendations, assessment, development, and evaluation (GRADE) was used to assess the certainty of evidence. Results: Ten studies involving 6,462 patients were included. 6,162 (95.36%) patients from 7 studies received adjuvant chemotherapy, whereas 296 (4.58%) patients from 3 studies underwent either adjuvant radiotherapy or chemoradiotherapy. When compared to patients who received neoadjuvant therapy and esophagectomy alone, adjuvant therapy groups experienced a significant overall survival benefit by 48% at 1-year (RR 0.52, 95%CI 0.41-0.65, P < 0.001, moderate certainty). This reduction in mortality was consistent at long-term 5-year follow-up (RR 0.91, 95%CI 0.87-0.96, P < 0.001, moderate certainty). Subgroup analysis on pathologic node positive patients demonstrated a consistent survival benefit at 1-year (RR 0.57, 95% CI 0.42-0.77, P < 0.001, moderate certainty) and 5-year (RR 0.89 95%CI 0.84-0.95, P < 0.001, moderate certainty). While adjuvant therapy presented no benefit for the T0-2 stage subgroup, patients with T3-4 disease experienced a significant reduction in mortality with the addition of adjuvant therapy at both 1-year (RR 0.51, 95% CI 0.41-0.63, P < 0.001, moderate certainty), and 5-years (RR 0.91, 95% CI 0.85-0.97, P = 0.005, moderate certainty). Due to incomplete reporting, the added benefit of adjuvant therapy was uncertain regarding DFS, locoregional recurrence, and distant recurrence. Conclusions: Adjuvant therapy after neoadjuvant treatment and curative esophagectomy provides improved OS at 1 and 5 years, but the benefit for DFS and locoregional/distant recurrence was uncertain due to limited reporting of these outcomes.

CT-based Radiomic Analysis for Prediction of Treatment Response of Salvage Chemoradiotherapy for Loco-regional Lymph Node Recurrence After Curative Esophagectomy

Objective: To investigate the capability of computed tomography (CT) radiomic features to predict the therapeutic response and local control of the loco-regional recurrence lymph node (LN) after curative esophagectomy by chemoradiotherapy (CRT).Methods: This retrospective study included 129 LN from 77 patients (training cohort: 102 LN from 59 patients; validation cohort: 27 LN from 18 patients) with postoperative esophageal squamous cell carcinoma (ESCC). The region of the tumor was contoured in pretreatment contrast-enhanced CT images. The least absolute shrinkage and selection operator (LASSO) with logistic regression was used to identify radiomic predictors in the training cohort. Model performance was evaluated using the area under the receiver operating characteristic curves (AUC). The Kaplan-Meier method was used to determine the local recurrence time of cancer.Results: Seven features were selected to construct a radiomics model for predicting therapeutic response. The AUCs in the training and validated cohorts were 0.777 (95%CI: 0.667–0.878) and 0.765(95%CI: 0.556–0.975), respectively. A significant difference of radiomic score (Rad-score) between the response and non-response was observed in the two cohorts (P < 0.001, 0.034, respectively). Two features were identified for classifying whether to relapse in two years. AUC was 0.857(95%CI: 0.780–0.935) in the training cohort. The local control time of the high Rad-score group was higher than the low group in both cohorts (P < 0.001 and 0.025, respectively). After the Cox regression analysis, the Rad-score indicated high-risk factors for local recurrence within two years.Conclusions: The radiomics approach can be used as a potential imaging biomarker to predict treatment response and local control of recurrence LN in ESCC patients.