Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Study protocol

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

Authors: JV Reynolds, SR Preston, B O’Neill, L Baeksgaard, SM Griffin, C Mariette, S Cuffe, M Cunningham, T Crosby, I Parker, K Hofland, G Hanna, LB Svendsen, CL Donohoe, C Muldoon, D O’Toole, C Johnson, N Ravi, G Jones, AK Corkhill, M Illsley, J Mellor, K Lee, M Dib, V Marchesin, M Cunnane, K Scott, P Lawner, S Warren, S O’Reilly, G O’Dowd, G Leonard, B Hennessy, R Mc Dermott

Published in: BMC Cancer | Issue 1/2017

Login to get access

Abstract

Background

Neoadjuvant 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.

Methods

This 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.

Discussion

This 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.
Appendix
Available only for authorised users
Literature
1.
2.
3.
Pennathur A, Gibson MK, Jobe BA, Luketich JD. Oesophageal carcinoma. Lancet. 2013;381(9864):400–12.CrossRefPubMed
4.
Siewert JR, Feith M, Werner M, Stein HJ. Adenocarcinoma of the esophagogastric junction: results of surgical therapy based on anatomical/topographic classification in 1,002 consecutive patients. Ann Surg. 2000;232(3):353–61.CrossRef
5.
Van Vliet E, Heijenbrok-Kal M, Hunink M, Kuipers E, Siersema P. Staging investigations for oesophageal cancer: a meta-analysis. Br J Cancer. 2008;98(3):547–57.CrossRefPubMedPubMedCentral
6.
Wouters MW, Gooiker GA, van Sandick JW, Tollenaar RA. The volume‐outcome relation in the surgical treatment of esophageal cancer. Cancer. 2012;118(7):1754–63.CrossRefPubMed
7.
Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, Gebski V. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12(7):681–92.CrossRefPubMed
8.
Kelsen DP, Ginsberg R, Pajak TF, Sheahan DG, Gunderson L, Mortimer J, Estes N, Haller DG, Ajani J, Kocha W. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med. 1998;339(27):1979–84.CrossRefPubMed
9.
Kelsen DP, Winter KA, Gunderson LL, Mortimer J, Estes NC, Haller DG, Ajani JA, Kocha W, Minsky BD, Roth JA. Long-term results of RTOG trial 8911 (USA Intergroup 113): a random assignment trial comparison of chemotherapy followed by surgery compared with surgery alone for esophageal cancer. J Clin Oncol. 2007;25(24):3719–25.CrossRefPubMed
10.
Working MRCOC. Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet. 2002;359(9319):1727–33.CrossRef
11.
Allum WH, Stenning SP, Bancewicz J, Clark PI, Langley RE. Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. J Clin Oncol. 2009;27(30):5062–7.CrossRefPubMed
12.
Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11–20.CrossRefPubMed
13.
Ychou M, Boige V, Pignon J-P, Conroy T, Bouché O, Lebreton G, Ducourtieux M, Bedenne L, Fabre J-M, Saint-Aubert B. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011;29(13):1715–21.CrossRefPubMed
14.
Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358(1):36–46.CrossRefPubMed
15.
Van Hagen P, Hulshof MCCM, van Lanschot JJB, Steyerberg EW, Van Berge Henegouwen MI, Wijnhoven BPL, Richel DJ, Nieuwenhuijzen GAP, Hospers GAP, Bonenkamp JJ, et al. Preoperative Chemoradiotherapy for Esophageal or Junctional Cancer. N Engl J Med. 2012;366(22):2074–84.CrossRefPubMed
16.
Oppedijk V, van der Gaast A, van Lanschot JJ, van Hagen P, van Os R, van Rij CM, van der Sangen MJ, Beukema JC, Rütten H, Spruit PH. Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials. J Clin Oncol. 2014;32(5):385–91.CrossRefPubMed
17.
Shapiro J, van Lanschot JJB, Hulshof MC, van Hagen P, van Berge Henegouwen MI, Wijnhoven BP, van Laarhoven HW, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015;16(9):1090–8.CrossRefPubMed
18.
Urba SG, Orringer MB, Turrisi A, Iannettoni M, Forastiere A, Strawderman M. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol. 2001;19(2):305–13.CrossRefPubMed
19.
Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TPJ. A Comparison of Multimodal Therapy and Surgery for Esophageal Adenocarcinoma. N Engl J Med. 1996;335(7):462–7.CrossRefPubMed
20.
Burmeister BH, Smithers BM, Gebski V, Fitzgerald L, Simes RJ, Devitt P, Ackland S, Gotley DC, Joseph D, Millar J. Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomised controlled phase III trial. Lancet Oncol. 2005;6(9):659–68.CrossRefPubMed
21.
Tepper J, Krasna MJ, Niedzwiecki D, Hollis D, Reed CE, Goldberg R, Kiel K, Willett C, Sugarbaker D, Mayer R. Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol. 2008;26(7):1086–92.CrossRefPubMedPubMedCentral
22.
Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer H-J, Riera-Knorrenschild J, Langer P, Engenhart-Cabillic R, Bitzer M, Königsrainer A. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009;27(6):851–6.CrossRefPubMed
23.
Sobin LH, Gospodarowicz MK, Wittekind C: TNM classification of malignant tumours: John Wiley & Sons; 2011
24.
25.
Dindo D, Demartines N, Clavien P-A. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205.
26.
Low DE, Alderson D, Cecconello I, Chang AC, et al. International Consensus on Standardisation of Data Collection for Complications Associated with Esophagectomy: Esophagectomy Complications Consensus Group. Ann Surg. 2015;262:286–94.CrossRefPubMed
27.
Mandard A-M, Dalibard F, Mandard J-C, Marnay J, Henry-Amar M, Petiot J-F, Roussel A, Jacob J-H, Segol P, Samama G, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994;73(11):2680–6.CrossRefPubMed
28.
29.
30.
Freidlin B, Korn EL, Gray R. A general inefficiency interim monitoring rule for randomised clinical trials. Clin Trials. 2010;7:197–208.CrossRefPubMed
31.
Association WM: Declaration of Helsinki. Ethical principles for medical research involving human subjects. 2009
32.
Editors ICoMJ. Defining the role of authors and contributors. Philadelphia: ICMJE; 2014.
33.
De Steur WO, Henneman D, Allim WH, Dikker JL, et al. Common data items in seven European oesophagogastric ancer srugery registeries: towards a European upper GI audit (EURECCA upper GI). Eur J Surg Oncol. 2014;40:325–9.CrossRefPubMed
34.
Moher D, Chan AW: SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials). Guidelines for Reporting Health Research: A User’s Manual 2014:56-67
Metadata
Title
ICORG 10-14: NEOadjuvant trial in Adenocarcinoma of the oEsophagus and oesophagoGastric junction International Study (Neo-AEGIS)
Authors
JV Reynolds
SR Preston
B O’Neill
L Baeksgaard
SM Griffin
C Mariette
S Cuffe
M Cunningham
T Crosby
I Parker
K Hofland
G Hanna
LB Svendsen
CL Donohoe
C Muldoon
D O’Toole
C Johnson
N Ravi
G Jones
AK Corkhill
M Illsley
J Mellor
K Lee
M Dib
V Marchesin
M Cunnane
K Scott
P Lawner
S Warren
S O’Reilly
G O’Dowd
G Leonard
B Hennessy
R Mc Dermott
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3386-2

Other articles of this Issue 1/2017

BMC Cancer 1/2017 Go to the issue

Research article

Prostate cancer-specific survival among warfarin users in the Finnish Randomized Study of Screening for Prostate Cancer

Research article

Association between tumour infiltrating lymphocytes, histotype and clinical outcome in epithelial ovarian cancer

Research article

Disparities of time trends and birth cohort effects on invasive breast cancer incidence in Shanghai and Hong Kong pre- and post-menopausal women

Research article

Quantitation of DNA methylation in Epstein-Barr virus–associated nasopharyngeal carcinoma by bisulfite amplicon sequencing

Research article

Higher educational attainment associated with reduced likelihood of abnormal cervical lesions among Zambian women - a cross sectional study

Research article

Overview of cancer incidence and mortality among people living with HIV/AIDS in British Columbia, Canada: Implications for HAART use and NADM development
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits