Immunonutrition supplementation for resectable gastric cancer during standard neoadjuvant chemotherapy of FLOT. A proof-of-concept protocol: I-SUPPLY

V. Pusceddu; C. Donisi; A. Pretta; F. Loi; R. Badas; P. Ziranu; M. Puzzoni; E. Lai; S. Mariani; E. Palmas; M. Pozzari; E. Cimbro; A.P. D’Agata; S. Pinto; F. Coghe; S. Bergamini; D. Fanni; G. Faa; T. Yoshino; M. Scartozzi

ESMO Gastrointestinal Oncology (Mar 2024)

Immunonutrition supplementation for resectable gastric cancer during standard neoadjuvant chemotherapy of FLOT. A proof-of-concept protocol: I-SUPPLY

V. Pusceddu,
C. Donisi,
A. Pretta,
F. Loi,
R. Badas,
P. Ziranu,
M. Puzzoni,
E. Lai,
S. Mariani,
E. Palmas,
M. Pozzari,
E. Cimbro,
A.P. D’Agata,
S. Pinto,
F. Coghe,
S. Bergamini,
D. Fanni,
G. Faa,
T. Yoshino,
M. Scartozzi

Affiliations

V. Pusceddu: Department of Medical Sciences and Public Health, Medical Oncology Unit, “Azienda Ospedaliero Universitaria” of Cagliari, University of Cagliari, Cagliari; Correspondence to: Dr Valeria Pusceddu, Department of Medical Science and Public Health, Medical Oncology Unit, Azienda Ospedaliero Universitaria of Cagliari, SS 554 bivio per Sestu, Monserrato (CA), Italy
C. Donisi: Department of Medical Sciences and Public Health, Medical Oncology Unit, “Azienda Ospedaliero Universitaria” of Cagliari, University of Cagliari, Cagliari
A. Pretta: Department of Medical Sciences and Public Health, Medical Oncology Unit, “Azienda Ospedaliero Universitaria” of Cagliari, University of Cagliari, Cagliari
F. Loi: Department of Medical Sciences and Public Health, Medical Oncology Unit, “Azienda Ospedaliero Universitaria” of Cagliari, University of Cagliari, Cagliari
R. Badas: Department of Surgery, Operative Unit of Diagnostic and Endoscopic Surgery, Cagliari University Hospital, Monserrato
P. Ziranu: Department of Medical Sciences and Public Health, Medical Oncology Unit, “Azienda Ospedaliero Universitaria” of Cagliari, University of Cagliari, Cagliari
M. Puzzoni: Department of Medical Sciences and Public Health, Medical Oncology Unit, “Azienda Ospedaliero Universitaria” of Cagliari, University of Cagliari, Cagliari
E. Lai: Department of Medical Sciences and Public Health, Medical Oncology Unit, “Azienda Ospedaliero Universitaria” of Cagliari, University of Cagliari, Cagliari
S. Mariani: Department of Medical Sciences and Public Health, Medical Oncology Unit, “Azienda Ospedaliero Universitaria” of Cagliari, University of Cagliari, Cagliari
E. Palmas: Department of Medical Sciences and Public Health, Medical Oncology Unit, “Azienda Ospedaliero Universitaria” of Cagliari, University of Cagliari, Cagliari
M. Pozzari: Department of Medical Sciences and Public Health, Medical Oncology Unit, “Azienda Ospedaliero Universitaria” of Cagliari, University of Cagliari, Cagliari
E. Cimbro: Department of Medical Sciences and Public Health, Medical Oncology Unit, “Azienda Ospedaliero Universitaria” of Cagliari, University of Cagliari, Cagliari
A.P. D’Agata: Department of Medical Sciences and Public Health, Medical Oncology Unit, “Azienda Ospedaliero Universitaria” of Cagliari, University of Cagliari, Cagliari
S. Pinto: Department of Surgery, Operative Unit of Diagnostic and Endoscopic Surgery, Cagliari University Hospital, Monserrato
F. Coghe: Clinical-Microbiological Laboratory, University Polyclinic, Cagliari
S. Bergamini: Department of Surgery, Operative Unit of Diagnostic and Endoscopic Surgery, Cagliari University Hospital, Monserrato
D. Fanni: Department of Medical Sciences and Public Health, Unit of Pathology, AOU Cagliari, University of Cagliari, Cagliari, Italy
G. Faa: Department of Medical Sciences and Public Health, Unit of Pathology, AOU Cagliari, University of Cagliari, Cagliari, Italy
T. Yoshino: Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa-shi, Chiba, Japan
M. Scartozzi: Department of Medical Sciences and Public Health, Medical Oncology Unit, “Azienda Ospedaliero Universitaria” of Cagliari, University of Cagliari, Cagliari

Journal volume & issue: Vol. 3
p. 100036

Abstract

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The ‘immune pattern’ of the esophagogastric junction and gastric cancer (GC) has been related to tumour progression and/or response to therapies. GC can be classified as immunogenic or immune-resistant based on the infiltration of the tumour microenvironment (TME) from different immune cells (ICs), the most significant of which are activated lymphocytes (a-Ly) CD8+ and CD4+. From the amount of a-Ly infiltration in TME, we can identify tumours with high Immunoscore (IS) which correlates with better prognosis in terms of disease-free survival and overall survival (OS). IC activation and consequent immunogenic TME requires high nutrient absorption and synthesis and accumulation of protein, lipid, and nucleotides. However, tumour cells (TCs) promote their own proliferation by stealing micronutrients to ICs, therefore leading to an immunosuppressive TME phenotype. This proof-of-concept protocol aims to assess whether a controlled enteral immune nutrition (EIN) supplementation can revert the TME in favour of ICs over TCs, in both auxotrophic and non-auxotrophic malignancies, witnessed by an increase in IS in surgical specimen over biopsy controls. Secondary endpoints are: (i) tumour regression grade assessment compared to historical data from FLOT4/AIO; (ii) combined proportion score ratio; (iii) relapse-free survival at 3 years and OS; and (iv) quality of life by the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire (EORTC QLQ)-30.

Published in ESMO Gastrointestinal Oncology

ISSN: 2949-8198 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.sciencedirect.com/journal/esmo-gastrointestinal-oncology

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