Induction chemotherapy followed by response evaluation and esophagectomy for advanced esophageal cancer.

INTRODUCTION: Patients with limited metastatic/advanced esophageal cancer not amenable for neoadjuvant therapy plus surgery have a poor prognosis and often receive palliative care. Alternatively, induction chemotherapy with response evaluation can be considered and in some patients surgery with curative intent may become feasible. The aim of this study was to evaluate the outcomes of patients treated with induction chemotherapy and to identify patient and/or tumor characteristics associated with survival. MATERIAL AND METHODS: Patients with esophageal or junctional cancer who underwent induction chemotherapy between 2005 and 2021 were identified from an institutional database of a tertiary referral center. Response to therapy was assessed by (18F-FDG PET)/CT. Response to therapy and treatment options, including surgery or palliation, were discussed in the multidisciplinary tumor board. Overall survival (OS) was calculated using the Kaplan Meier method. Uni- and multivariable analyses were performed to identify prognostic factors for survival. RESULTS: 238 patients were identified. The majority had esophageal adenocarcinoma (68.9 %) and were treated with a taxane/platinum-based chemotherapy (79.4 %). Response evaluation was performed in 233 patients and 154 of 238 patients (64.7 %) underwent surgical exploration. Resection was performed in 127 patients (53.4 %) resulting in a median and 5-year OS of 26.3 months (95 % CI 18.8-33.8) and 29.6 %, respectively. Presence of T4b (HR = 2.01, 95 % CI 1.02-3.92) and poorly differentiated tumor (HR = 1.45, 95 % CI 1.02-2.10) was associated with worse survival (p = 0.04). CONCLUSION: In carefully selected patients with advanced disease not amenable for standard curative treatment, induction chemotherapy followed by esophagectomy may result in a 5-year overall survival of approximately 30 %.

Association between Paclitaxel Clearance and Tumor Response in Patients with Esophageal Cancer.

Inter-individual variability in paclitaxel pharmacokinetics may play a role in the response to chemotherapy. Therefore, we studied the association between paclitaxel clearance and treatment response in patients with esophageal cancer. All patients who received paclitaxel (plus carboplatin) treatment for esophageal cancer between 2007 and 2013 were included. The treatment was given as neoadjuvant chemoradiotherapy (nCRT), induction chemotherapy (iCT), or palliative chemotherapy (pCT). The treatment response was assessed by the tumor regression grade (TRG) or by the RECIST1.1 criteria, respectively. The unbound paclitaxel clearance (CL) was estimated with NONMEM. The log-transformed clearance was related to response with ANOVA and independent sample t-tests. A total of 166 patients were included, of whom 113 received nCRT, 23 iCT and 30 pCT. In patients receiving nCRT, paclitaxel clearance was not associated with tumor regression grade (p-value = 0.25), nor with pathologically complete response (geometric mean 561.6 L/h) and residual disease (geometric mean 566.1 L/h, p-value = 0.90). In patients who underwent iCT or pCT, also no association between paclitaxel clearance and RECIST outcome was identified (iCT: p-value = 0.08 and pCT: p-value = 0.81, respectively). In conclusion, systemic paclitaxel exposure was not associated with response to common paclitaxel-based treatment regimens for esophageal cancer. Future studies should focus on tumor exposure in relation to systemic exposure and treatment outcome.

P53 and SOX2 Protein Expression Predicts Esophageal Adenocarcinoma in Response to Neoadjuvant Chemoradiotherapy.

OBJECTIVE: The aim of the study was to investigate the association between p53, SOX2, and CD44 protein expression and tumor response, and to validate potential predictive biomarker(s) in an independent cohort. BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery has become a standard of care for esophageal adenocarcinoma (EAC). However, the response to nCRT is highly variable among patients. METHODS: EAC patients who underwent nCRT and surgery, between January 2003 and December 2014 at the Erasmus University Medical Center, were included and divided into a primary (n = 77) and a validation cohort (n = 70). P53, SOX2, and CD44 expression was detected by immunohistochemistry in pretreatment tumor biopsies, and scored independently by 2 investigators. Response to nCRT was assessed based on tumor regression grade (TRG) in the resection specimen. RESULTS: Forty-one (53%) patients in the primary cohort and 33 (47%) patients in the validation cohort showed major response (TRG1 or TRG2) in the resection specimen. Aberrant p53 and absence of SOX2 were associated with major response in the primary cohort: adjusted odds ratio (OR) 6.3 [95% confidence interval (CI), 1.3-30.1) and adjusted OR 4.1 (95% CI, 1.4-12.4), respectively. The same was true for the validation cohort (p53: adjusted OR 8.6; 95% CI, 0.93-80.9 and SOX2: adjusted OR 6.1; 95% CI, 1.6-23.4). The highest probability of a major response was seen in patients with concurrent aberrant p53 and absence of SOX2 expression, with an OR of 6.7 (95% CI, 2.1-21.4) and 6.2 (95% CI, 1.8-21.2) in the primary and validation cohort. CONCLUSIONS: Pattern of p53 and particularly SOX2 protein expression in EAC predicts response to nCRT. These biomarkers may help to individualize treatment in EAC patients.

Leaving a mobilized thoracic esophagus in situ when incurable cancer is discovered intraoperatively.

BACKGROUND: Occasionally incurable cancer is encountered after completion of the thoracic (first) phase of a three-phase esophagectomy. The outcome of aborting the operation at this stage, leaving the mobilized thoracic esophagus in situ, is unknown. METHODS: A multicenter retrospective analysis was performed of patients in whom a completely mobilized thoracic esophagus was left in situ when incurable disease was discovered intraoperatively. The occurrence of esophageal necrosis or perforation, mortality, and all other adverse events were recorded and graded by severity. RESULTS: Some 18 patients were included. The median admission time was 9 days. All patients had resumed oral intake at discharge, except for 1 patient who was fed through a nasojejunal tube. After the operation, the median overall survival was 2.9 months. Postoperatively, 7 patients (39%) experienced major surgical adverse events, and 11 patients (61%) had no or only minor adverse events. Major adverse events were associated with the patient's death in 6 patients (33%), within 5 to 34 days postoperatively. Esophageal perforation or ischemia developed in 4 patients (22%) and 1 patient (6%), respectively. No predictive factors could be identified. CONCLUSIONS: Leaving a completely mobilized thoracic esophagus in situ when incurable cancer was discovered intraoperatively was a successful strategy in more than half of the patients. However, one third experienced major adverse events leading to mortality.

New therapeutic strategies for squamous cell cancer and adenocarcinoma.

This paper presents commentaries on neoadjuvant treatment esophagectomy; the prognostic and predictive effects of single nucleotide polymorphisms (SNP) in the multimodality therapy of esophageal cancer; optimal preoperative treatment prior to surgery for esophageal cancer; a possible role for trastuzumab in treating esophageal adenocarcinoma or any esophageal dysplasia/intra-epithelial neoplasia; surgery after chemoradiation in resectable esophageal cancer; whether para-aortic lymph node dissection should be performed in esophagogastric junction (EGJ) tumors; and transhiatal esophagectomy in treatment of the esophageal cancer.