Pathologic Complete Response Is an Independent Predictor of Improved Survival Following Neoadjuvant Chemoradiation for Esophageal Adenocarcinoma.

INTRODUCTION: Reports of improved survival in patients with pathologic complete response (pCR) to neoadjuvant therapy for esophageal and gastroesophageal junction (GEJ) adenocarcinoma is extrapolated from heterogeneous studies that include squamous cell histology. We sought to determine if pCR is associated with a survival advantage in a homogenous group of patients with esophageal adenocarcinoma. METHODS: This is a single institution analysis of all patients with T2-T4 or node positive esophageal adenocarcinoma treated with neoadjuvant chemoradiotherapy and esophagectomy between 2004 and 2014. Patients were divided into two groups based on pathological response, pCR vs. incomplete pathological response (iPR). Survival outcomes were evaluated using standard Kaplan-Meier methods and multivariable Cox regression models. RESULTS: A total of 205 patients were included in the study: 38 (19 %) patients with pCR and 167 patients (81 %) with iPR. The two groups were similar with respect to clinical stage, age, gender, comorbid conditions, ECOG status, smoking, and alcohol use. Patients in the pCR group had a higher percentage of tumors located in middle third of esophagus (11 vs. 2 %, p = 0.04) while tumor grade was similar in both groups. Median follow-up was 50 months, range 2-109 months. The 3-year overall (OS) and recurrence-free survival (RFS) for iPR was 48 and 39 %, respectively, vs. 86 and 80 % for pCR group, respectively. CONCLUSION: This analysis of a cohort of homogeneous patients with esophageal adenocarcinoma undergoing multimodality therapy showed that pCR is an independent predictor of improved RFS and OS. This data contributes to a growing body of evidence highlighting the benefits of neoadjuvant therapy specific to esophageal adenocarcinoma particularly when pCR is achieved.

Association Between Clinically Staged Node-Negative Esophageal Adenocarcinoma and Overall Survival Benefit From Neoadjuvant Chemoradiation.

IMPORTANCE: While neoadjuvant chemoradiation for esophageal cancer improves oncologic outcomes for a broad group of patients with locally advanced and/or node-positive tumors, it is less clear which specific subset of patients derives most benefit in terms of overall survival (OS). OBJECTIVE: To determine whether neoadjuvant chemoradiation based on esophageal adenocarcinoma histology has similar oncologic outcomes for patients treated with surgery alone when stratified by clinical nodal status. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis using the American College of Surgeons National Cancer Database from 1998 to 2006. Patients with esophageal adenocarcinoma histology and clinical stage T1bN1-N3 or T2-T4aN-/+M0 were divided into 2 treatment groups: (1) neoadjuvant chemoradiation followed by surgery and (2) surgery alone. Subset analysis within each treatment group was performed for clinically node-negative patients (cN-) vs node-positive patients (cN+) in conjunction with pathological nodal status. A propensity score-adjusted analysis, which included patient demographics, comorbidity status, and clinical T stage, was also performed. MAIN OUTCOME AND MEASURES: The primary outcome was 3-year OS. Secondary outcomes included margin status, postoperative length of stay, unplanned readmission rate, and 30-day mortality. RESULTS: A total of 1309 patients were identified, of whom 539 received neoadjuvant chemoradiation followed by surgery and 770 received surgery alone. Of the 1309 patients, 41.2% (n = 539) received neoadjuvant chemoradiation and 47.2% (n = 618) were cN+. Median follow-up for the entire cohort was 73.3 months (interquartile range, 64.1-93.5 months). The 3-year OS was better for neoadjuvant chemoradiation followed by surgery compared with surgery alone (49% vs 38%, respectively; P < .001). Stratifying based on clinical nodal status, the propensity score-adjusted OS was significantly better for cN+ patients who received neoadjuvant chemoradiation (hazard ratio, 0.52; 95% CI, 0.42-0.66; P < .001). In contrast, there was no difference in OS for cN- patients based on treatment (hazard ratio, 0.84; 95% CI, 0.65-1.10; P = .22). CONCLUSIONS AND RELEVANCE: Patients with cN+ esophageal adenocarcinoma benefit significantly from neoadjuvant chemoradiation. However, patients with cN- tumors treated with neoadjuvant chemoradiation plus surgery do not derive a significant OS benefit compared with surgery alone. This finding may have significant implications on the use of neoadjuvant chemoradiation in patients with cN- disease.

Role of Repeat 18F-Fluorodeoxyglucose Positron Emission Tomography Examination in Predicting Pathologic Response Following Neoadjuvant Chemoradiotherapy for Esophageal Adenocarcinoma.

IMPORTANCE: Predicting complete pathologic response (CPR) preoperatively can significantly affect surgical decision making. There are conflicting data regarding positron emission tomography computed tomography (PET CT) characteristics and the ability of PET CT to predict pathologic response following neoadjuvant chemoradiotherapy in esophageal adenocarcinoma because most existing studies that include squamous histology have limited numbers and use nonstandardized PET CT imaging. OBJECTIVE: To determine if PET CT characteristics are associated with CPR in patients undergoing trimodality treatment for esophageal adenocarcinoma. DESIGN, SETTING, AND PARTICIPANTS: A retrospective medical record review was conducted at a large tertiary cancer center from a prospectively maintained database from January 1, 2005, to December 31, 2012. Inclusion criteria were patients undergoing esophagectomy for locally advanced esophageal adenocarcinoma post-neoadjuvant chemoradiotherapy with 2 standardized PET CT studies done at our institution (pre-neoadjuvant chemoradiotherapy and post-neoadjuvant chemoradiotherapy) for review. Data collected included clinical, pathologic, imaging, and treatment characteristics. MAIN OUTCOME AND MEASURE: The primary study outcome was the association of PET CT characteristics with histologic confirmed pathologic response. RESULTS: Of the total participants, 77 patients met the inclusion criteria. Twenty-two patients (28.6%) had CPR vs 55 patients (71.4%) who had incomplete pathologic response. The 2 groups were similar in age, sex, race/ethnicity, comorbid conditions, Eastern Cooperative Oncology Group status, tumor grade, chemotherapy, and radiation regimen and days between the 2 PET CTs. The mean prestandardized uptake variable (SUV; 14.5 vs 11.2; P = .05), δ SUV (10.3 vs 5.4; P = .02), and relative δ SUV (0.6 vs 0.4; P = .02) were significantly higher in those with CPR vs incomplete pathologic response. Using the Youden Index, a δ SUV value less than 45% was predictive of residual disease with a positive predictive value of 91.7% (95% CI, 73-99; P < .05). CONCLUSIONS AND RELEVANCE: To our knowledge, this is the largest study examining the role of PET CT characteristics in esophageal adenocarcinoma for patients undergoing neoadjuvant chemoradiotherapy that demonstrates that δ SUV of less than 45% is associated with patients with residual disease but not CPR. Based on the findings from our study, the current recommendation is still surgical resection regardless of the posttherapy PET SUV in the primary tumor. However, our study highlights the ability to detect patients with residual disease and the need to critically evaluate these patients for consideration of additional therapies.