Induction FOLFOX and PET-Directed Chemoradiation for Locally Advanced Esophageal Adenocarcinoma

Abstract

Objective: To compare the efficacy and safety of induction FOLFOX followed by PET-directed nCRT, induction CP followed by PET-directed nCRT, and nCRT with CP alone in patients with EAC. Summary of Background Data: nCRT with CP is a standard treatment for locally advanced EAC. The results of cancer and leukemia group B 80803 support the use of induction chemotherapy followed by PET-directed chemo-radiation therapy. Methods: We retrospectively identified all patients with EAC who underwent the treatments above followed by esophagectomy. We assessed incidences of pathologic complete response (pCR), near-pCR (ypN0 with ≥90% response), and surgical complications between treatment groups using Fisher exact test and logistic regression; disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan–Meier method and evaluated using the log-rank test and extended Cox regression. Results: In total, 451 patients were included: 309 (69%) received induction chemotherapy before nCRT (FOLFOX, n = 70; CP, n = 239); 142 (31%) received nCRT with CP. Rates of pCR (33% vs. 16%, P = 0.004), near-pCR (57% vs. 33%, P < 0.001), and 2-year DFS (68% vs. 50%, P = 0.01) were higher in the induction FOLFOX group than in the induction CP group. Similarly, the rate of near-pCR (57% vs. 42%, P = 0.04) and 2-year DFS (68% vs. 44%, P < 0.001) were significantly higher in the FOLFOX group than in the no-induction group. Conclusions: Induction FOLFOX followed by PET-directed nCRT may result in better histopathologic response rates and DFS than either induction CP plus PET-directed nCRT or nCRT with CP alone.

Exploring FLOT- and FOLFOX-Based total neoadjuvant therapy for patients with locally advanced gastroesophageal cancers

“…Taken together, our results in combination with other recently reported, support the ongoing continued evaluation of TNT in patients with locally advanced GE/G cancer using either FLOT or FOLFOX [28][29][30]. Given that rates of pCR are correlated with recurrence-free survival outcomes, the sum of our experience with FOLFIRINOX, FLOT, and FOLFOX in combination with those from recently reported studies suggests an early indicator that the TNT approach may be effective [25,26,28,31]. However, studies have yet to conclusively determine if survival outcomes can be improved with increased treatment intensity by delivering all chemotherapy prior to CRT and surgery.…”

“…However, less than half of patients completed all post-operative FLOT. Although current clinical guidelines recommend post-and peri-operative chemotherapy and/or neoadjuvant CRT for resectable GE/G tumors, purely preoperative (including image guided) approaches combining both systemic chemotherapy and CRT may improve therapy completion rates and elicit tumor down-staging before surgery [24,25].…”

Commentary: Crossing off CROSS for treatment of esophageal adenocarcinoma

“…Data from CALGB 80803 and my institution further confirm that carboplatin-paclitaxel is a suboptimal regimen to achieve micrometastatic control in EAC. 7,8 Radiation may improve local control in cases of lower-quality surgical resections (almost half of patients in the CROSS trial underwent transhiatal esophagectomy! ), but the prospect of preserving the esophagus through the use of chemoradiation-which the authors argue is possible-appears to be a mirage as elusive as the meaning Although CROSS retains a role for esophageal squamous cell carcinoma, better systemic options exist for adenocarcinoma, for which high-quality surgical resection remains a mainstay of treatment.…”

Five decades of progress in surgical oncology: Tumors of the lung and esophagus

“…The OS benefit of neoadjuvant chemoRT before surgical resection was established in the CROSS trial which randomized patients with locally advanced ESC and EAC to ChemoRT (using carboplatin and paclitaxel) plus resection versus esophagectomy alone 36 . More recent studies have established oxaliplatin and 5‐fluorouracil (FOLFOX) in combination with radiotherapy as effective and better tolerated neoadjuvant treatment 37 . Overall though, neoadjuvant therapy for locally advanced esophageal cancer has remained static for the past decade.…”

“…36 More recent studies have established oxaliplatin and 5-fluorouracil (FOLFOX) in combination with radiotherapy as effective and better tolerated neoadjuvant treatment. 37 Overall though, neoadjuvant therapy for locally advanced esophageal cancer has remained static for the past decade. Though trastuzumab has proven and important addition to the treatment of HER2-positive metastatic esophageal cancers, it failed to improve DFS in a recent RCT when added to standard preoperative chemoRT.…”