ICORG 10-14: NEOadjuvant trial in Adenocarcinoma of the oEsophagus and oesophagoGastric junction International Study (Neo-AEGIS)

Abstract

BackgroundNeoadjuvant therapy is increasingly the standard of care in the management of locally advanced adenocarcinoma of the oesophagus and junction (AEG). In randomised controlled trials (RCTs), the MAGIC regimen of pre- and postoperative chemotherapy, and the CROSS regimen of preoperative chemotherapy combined with radiation, were superior to surgery only in RCTs that included AEG but were not powered on this cohort. No completed RCT has directly compared neoadjuvant or perioperative chemotherapy and neoadjuvant chemoradiation. The Neo-AEGIS trial, uniquely powered on AEG, and including comprehensive modern staging, compares both these regimens.MethodsThis open label, multicentre, phase III RCT randomises patients (cT2-3, N0-3, M0) in a 1:1 fashion to receive CROSS protocol (Carboplatin and Paclitaxel with concurrent radiotherapy, 41.4Gy/23Fr, over 5 weeks). The power calculation is a 10% difference in favour of CROSS, powered at 80%, two-sided alpha level of 0.05, requiring 540 patients to be evaluable, 594 to be recruited if a 10% dropout is included (297 in each group). The primary endpoint is overall survival, with a minimum 3-year follow up. Secondary endpoints include: disease free survival, recurrence rates, clinical and pathological response rates, toxicities of induction regimens, post-operative pathology and tumour regression grade, operative in-hospital complications, and health-related quality of life. The trial also affords opportunities for establishing a bio-resource of pre-treatment and resected tumour, and translational research.DiscussionThis RCT directly compares two established treatment regimens, and addresses whether radiation therapy positively impacts on overall survival compared with a standard perioperative chemotherapy regimen Sponsor: Irish Clinical Research Group (ICORG).Trial registration NCT01726452. Protocol 10-14. Date of registration 06/11/2012.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3386-2) contains supplementary material, which is available to authorized users.

Radiomics in esophageal and gastric cancer

“…Trimodality therapy for esophageal and esophago-gastric cancer combining neoadjuvant chemo-and radiation-therapy in addition to surgery may also be superior to neoadjuvant chemotherapy alone in a selected patient population [8]. The CROSS trial [6] comparing neoadjuvant chemoradiotherapy plus surgery with surgery alone in patients with esophageal and esophago-gastric cancer showed a superior overall-survival of 49 vs. 24 months, hazard ratio 0.657, p = 0.003, and a pathological complete response rate of 29%, for patients with multi-modality treatment with no increase in surgical mortality (4% in surgery and trimodality groups, respectively).…”

Surgical treatment of esophageal cancer in the era of multimodality management

“…The MAGIC study and the French FNCLCC/FFCD 9703 study were the first to show an overall survival benefit for perioperative chemotherapy in patients with lower esophageal, gastroesophageal junction (GEJ), and gastric adenocarcinoma. After these results, the CROSS study combined carboplatin/paclitaxel with 41.4 Gy radiation and demonstrated a 14% increase in 5‐year overall survival for patients with esophageal cancer (both squamous cell carcinoma and adenocarcinoma) treated with neoadjuvant chemoradiotherapy followed by surgery compared with surgery alone . However, the recently presented phase III FLOT 4 trial has shown that the FLOT regimen (docetaxel, oxaliplatin, leucovorin, and 5‐fluorouracil (5‐FU)) improves the outcome of patients with esophageal adenocarcinoma and locoregional disease as compared with the ECF/ECX triplet (epirubicin, cisplatin, and 5‐FU or capecitabine) .…”

“…Currently, several randomized trials comparing perioperative chemotherapy and neoadjuvant chemoradiotherapy are being undertaken. The NeoAegis study compares CROSS versus MAGIC and the German ESOPEC study compares FLOT versus CROSS in patients with esophageal adenocarcinoma . The Chinese CMISG1701 study compares overall survival between neoadjuvant chemotherapy (cisplatin/paclitaxel) with neoadjuvant chemoradiotherapy (cisplatin/paclitaxel with 40 Gy radiation), both followed by esophagectomy for locally advanced resectable esophageal squamous cell carcinoma .…”

Neoadjuvant Radiochemotherapy for Patients with Locally Advanced Esophagogastric Junction Adenocarcinoma

“…Currently, there is no consensus regarding the management of patients with advanced local esophagogastric junction adenocarcinomas. If there is unanimity for Siewert I tumors regarding surgical technique, for Siewert II and III tumors there is still a matter of debate regarding surgical approach, operative risks that may occur and the postoperative complications (1).…”