Immunonutrition to improve the quality of life of upper gastrointestinal cancer patients undergoing neoadjuvant treatment prior to surgery (NEOIMMUNE): double-blind randomized controlled multicenter clinical trial. - 2025
Immunonutrition to improve the quality of life of upper gastrointestinal cancer patients undergoing neoadjuvant treatment prior to surgery (NEOIMMUNE): double-blind randomized controlled multicenter clinical trial.
[en] BACKGROUND: Malnutrition is common with esophagogastric cancers and is associated with negative outcomes. We aimed to evaluate if immunonutrition during neoadjuvant treatment improves patient's health-related quality of life (HRQOL) and reduces postoperative morbidity and toxicities during neoadjuvant treatment.
METHODS: A multicenter double-blind randomized controlled trial (RCT) was undertaken. Included patients had untreated nonmetastatic esophagogastric tumor, aged 18 ≥ years with a life expectancy of >3 months. The study was powered for 80% power to detect a clinically relevant difference in EORTC-QLQC30 with standard deviation of 15 between groups. Primary end point was the quality of life as measured by the global health status at 30 days after surgery. An intention-to-treat analysis was employed.
RESULTS: The study was terminated at the interim analysis stage. About 300 patients were randomized: 149 to the IMPACT group and 151 to the control-formula group. Patient groups were well-balanced in terms of age, sex, body mass index, WHO performance status, and clinical tumor stage. Analysis of the primary end point for the study of global health status at 30-day postoperatively failed to show any significant differences between the groups (55.4 ± 18.6 [IMPACT] vs. 55.9 ± 19.8 [control]; P = 0.345). No significant differences between the groups were detected in the majority of domains from EORTC QLQC30 and OG25 tools after neoadjuvant therapy and 30 days postoperatively. Finally, no significant differences were seen between groups in neoadjuvant therapy or postoperative complications, or tumor response.
CONCLUSION: The results of this multicenter double-blind RCT fail to demonstrate any HRQOL benefits to the utilization of immunonutrition during neoadjuvant therapy in patients with esophagogastric cancer.
Disciplines :
Oncology
Author, co-author :
Markar, Sheraz ; Nuffield Department of Surgery, University of Oxford, Oxford, UK
Mariette, Christophe; Department of Digestive and Oncological Surgery, Claude Huriez Hospital, Chu Lille, Lille, France
Bonnetain, Frank; Methodology and Quality of Life Unit in Cancer, INSERM UMR 1098, University Hospital of Besançon, Besançon, France
Lundell, Lars; Department of Clinical Sciences Intervention and Technology, Karolinska institutet, Stockholm, Sweden
Rosati, Riccardo; Department of Gastrointestinal Surgery, San Raffaele Scientific Institute, Vita e Salute University, Milan, Italy
de Manzoni, Giovanni; General and Upper GI Surgery Division, University of Verona, Verona, Italy
Bonavina, Luigi; Division of General Surgery IRCCS Policlinico San Donato, Department of Biomedical Science for Health, University of Milan, Milan, Italy
Tucker, Olga; Department of Surgery, University of Birmingham, Birmingham, UK
Plum, Patrick; Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne, Germany
D'Journo, Xavier Benoit; Department of Thoracic Surgery, Hôpital Nord, Aix-Marseille Université, Assistance Publique Hôpitaux de Marseille, Marseille, France
Van Daele, Daniel ; Université de Liège - ULiège > Département des sciences cliniques
Cogill, Geoff; Department of Oncology, University Hospitals Plymouth NHS Trust, Plymouth, UK
Santi, Stefano; Esophageal Surgery Unit, Gastroenterology Department, Regional Referral Center for Diagnosis and Treatment of Diseases of Esophagus, "Nuovos. Chiara" Hospital, Pisa, Italy
Farran, Leandres; Digestive Surgery Department, Hospital Universitari de Bellvitge, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
Iranzo, Vega; Medical Oncology Department, Hospital General Universitario de Valencia, Valencia, Spain
Pera, Manuel; Sección de Cirugía Gastrointestinal, Servicio de Cirugía, Hospital Universitario del Mar, Institut Hospital del Mar d'Investigacións Mèdiques (IMIM), Universitat Autònoma de Barcelona, Barcelona, Spain
Veziant, Julie; Department of Digestive and Oncological Surgery, Claude Huriez Hospital, Chu Lille, Lille, France ; Univ. Lille, CNRS, Inserm, Chu Lille, UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, Lille, France
Piessen, Guillaume ; Department of Digestive and Oncological Surgery, Claude Huriez Hospital, Chu Lille, Lille, France ; Univ. Lille, CNRS, Inserm, Chu Lille, UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, Lille, France
Immunonutrition to improve the quality of life of upper gastrointestinal cancer patients undergoing neoadjuvant treatment prior to surgery (NEOIMMUNE): double-blind randomized controlled multicenter clinical trial.
Bodger K, Eastwood P G, Manning S I et al. Dyspepsia workload in urban general practice and implications of the British Society of Gastroenterology Dyspepsia guidelines (1996). Aliment Pharmacol Ther 2000; 14: 413–20.
Shawihdi M, Thompson E, Kapoor N et al. Variation in gastroscopy rate in English general practice and outcome for oesophagogastric cancer: retrospective analysis of hospital episode statistics. Gut 2014; 63: 250–61.
Cederholm T, Jensen G L, Correia M et al. GLIM criteria for the diagnosis of malnutrition - a consensus report from the global clinical nutrition community. Clin Nutr 2019; 38: 1480–1.
Elliott J A, Casey S, Murphy C F et al. Risk factors for loss of bone mineral density after curative esophagectomy. Arch Osteoporos 2019; 14: 6.
Rietveld S C M, Witvliet-van Nierop J E, Ottens-Oussoren K et al. The prediction of deterioration of nutritional status during chemoradiation therapy in patients with esophageal cancer. Nutr Cancer 2018; 70: 229–35.
Jarvinen T, Ilonen I, Kauppi J et al. Loss of skeletal muscle mass during neoadjuvant treatments correlates with worse prognosis in esophageal cancer: a retrospective cohort study. World J Surg Oncol 2018; 16: 27.
Muscaritoli M, Anker S D, Argiles J et al. Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elabo- rated by special interest groups (SIG) “cachexia-anorexia in chronic wasting diseases” and “nutrition in geriatrics”. Clin Nutr 2010; 29: 154–9.
Anandavadivelan P, Lagergren P. Cachexia in patients with esophageal cancer. Nat Rev Clin Oncol 2016; 13: 185–98.
Hynes O, Anandavadivelan P, Gossage J et al. The impact of pre- and post-operative weight loss and body mass index on prognosis in patients with esophageal cancer. Eur J Surg Oncol 2017; 43: 1559–65.
Fujiya K, Kawamura T, Omae K et al. Impact of malnutrition after gastrectomy for gastric cancer on long-term survival. Ann Surg Oncol 2018; 25: 974–83.
Markar S, Gronnier C, Duhamel A et al. The impact of severe anastomotic leak on long-term survival and cancer recurrence after surgical resection for esophageal malignancy. Ann Surg 2015; 262: 972–80.
Rutegard M, Lagergren P, Rouvelas I et al. Surgical complications and long-term survival after esophagectomy for cancer in a nationwide Swedish cohort study. Eur J Surg Oncol 2012; 38: 555–61.
Lagergren P, Schandl A, Aaronson N K et al. Cancer survivor-ship: an integral part of Europe’s research agenda. Mol Oncol 2019; 13: 624–35.
Wikman A, Johar A, Lagergren P. Presence of symptom clusters in surgically treated patients with esophageal cancer: implications for survival. Cancer 2014; 120: 286–93.
Mariette C. Immunonutrition. J Visc Surg 2015; 152: S14–7.
Aiko S, Kumano I, Yamanaka N et al. Effects of an immune-enhanced diet containing antioxidants in esophageal cancer surgery following neoadjuvant therapy. Dis Esophagus 2012; 25: 137–45.
Cerantola Y, Hubner M, Grass F et al. Immunonutrition in gastrointestinal surgery. Br J Surg 2011; 98: 37–48.
Mazaki T, Ishii Y, Murai I. Immunoenhancing enteral and parenteral nutrition for gastrointestinal surgery. Ann Surg 2015; 261: 662–9.
Marano L, Porfidia R, Pezzella M et al. Clinical and immunological impact of early postoperative enteral immnunonutrition after total gastrectomy in gastric cancer patients: a prospective randomized study. Ann Surg Oncol 2013; 20: 3912–8.
Braga M, Gianotti L, Radaelli G et al. Perioperative immunonutrition in patients undergoing cancer surgery: results of a randomized double blind phase 3 trial. Arch Surg 1999; 134: 428–33.
Van Hagen P, Hulshof M C, van Lanschot J J et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 2012; 366(22): 2074–84.
Detsky A S, McLaughlin J R, Baker J P et al. What is subjective global assessment of nutritional status? JEPN J Parenter Enteral Nutr 1987; 11: 8–13.
Arends J, Bachmann P, Baracos V et al. ESPEN expert group recommendations for action against cancer-related malnutrition. Clin Nutr 2017; 36: 1187–96.
Weimann A, Braga M, Carli F et al. ESPEN guideline: clinical nutrition in surgery. Clin Nutr 2017; 36: 623–50.
Brenkman H J F, Tegels J J W, Ruurda J P et al. Factors influencing health-related quality of life after gastrectomy for cancer. Gastric Cancer 2018; 21: 524–32.
Kauppila J H, Ringborg C, Johar A, Lagergren J, Lagergren P. Health-related quality of life after gastrectomy, esophagectomy, and combined esophagogastrectomy for gas-troesophageal junction adenocarcinoma. Gastric Cancer 2018; 21: 533–41.
Mudge L A, Watson D I, Smithers B M et al. Multicentre factorial randomized clinical trial of perioperative immunonutrition versus standard nutrition for patients undergoing surgical resection of oesophageal cancer. Br J Surg 2018; 105: 1262–72.
Sultan J, Griffin S M, Di Franco F et al. Randomized clinical trial of omega-3 fatty acid-supplemented enteral nutrition versus standard enteral nutrition in patients undergoing oesophagogastric cancer surgery. Br J Surg 2012; 99: 346–55.
Hubner M, Cerantola Y, Grass F et al. Preoperative immunonutrition in patients at nutritional risk: results of a double-blinded randomized clinical trial. Eur J Clin Nutr 2012; 66: 850–5.
Kanekiyo S, Takeda S, Iida M et al. Efficacy of perioperative immunonutrition in esophageal cancer patients undergoing esophagectomy. Nutrition 2019; 59: 96–102.
Low D E, Allum W, De Manzoni G et al. Guidelines for perioperative care in esophagectomy: enhanced recovery after surgery (ERAS®) society recommendations. World J Surg 2019; 43: 299–330.
Mortensen K, Nilsson M, Slim K et al. Enhanced recovery after surgery (ERAS®) group. Consensus guidelines for enhanced recovery after gastrectomy: enhanced recovery after surgery (ERAS®) society recommendations. Br J Surg 2014; 101: 1209–29.
Avery K N, Metcalfe C, Berrisford R et al. The feasibility of a randomized controlled trial of esophagectomy for esophageal cancer – the ROMIO (randomized oesophagectomy: minimally invasive or open) study: protocol for a randomized controlled trial. Trials 2014; 15: 200.
Fearon K C H. Cancer cachexia: developing multimodal therapy for a multidimensional problem. Eur J Cancer 2008; 44(8): 1124–32.
Brown C, Laird B J A, Wigmore S J, Skipworth R J E. Understanding cancer cachexia and its implications in upper gastrointestinal cancers. Treat Options Oncol 2022; 23: 1732–47.
Weimann A, Braga M, Carli F et al. ESPEN practical guideline: clinical nutrition in surgery. Clin Nutr 2021; 40(7): 4745–61.
