BACKGROUND: Perioperative chemotherapy is a recommended treatment approach for localised oesophago-gastric junction adenocarcinoma, but not all patients respond to neoadjuvant chemotherapy. Early identification of non-responders and treatment adaptation in the preoperative period could improve outcomes. GastroPET is a national, multicentre phase II trial evaluating a 18FDG-PET/CT-guided preoperative treatment strategy with the R0 resection rate as a primary endpoint. Here, we report on the accuracy of the methodology, the feasibility of the study design and patient safety data after enrolment of the first 63 patients. METHODS: Patients with locally advanced oesophago-gastric junction adenocarcinoma (Siewert I - III) stage Ib-IIIc underwent baseline 18FDG-PET/CT scanning and re-evaluation after 14 days of oxaliplatinum-5FU-(docetaxel) chemotherapy. Responders were defined by a ⩾ 35% decrease in tumour FDG standardised uptake value (SUV)average from baseline. Responders continued with the same chemotherapy for 2 to 3 months prior to surgery. PET-non-responders switched to preoperative chemoradiotherapy [weekly carboplatin and paclitaxel with concurrent radiotherapy (45 Gy in 25 fractions)]. Here, we aim to confirm the feasibility of FDG-PET-based response assessment in a multicenter setting and to compare local versus central reading. In addition, we report on the feasibility of the study conduct and patient safety data. RESULTS: A total of 64 patients received baseline and sequential 14-day 18FDG-PET/CT scanning. And, 63 were allocated to the respective treatment arm according to PET-response [35 (56%) responders and 28 (44%) non-responders]. The concordance of local versus central reading of SUV changes was 100%. Until the date of this analysis, 47 patients (28 responders and 19 non-responders) completed surgery. Postoperative complications of grade ⩾ 3 (Common Terminology Criteria for Adverse Events, CTCAE Version 5.0) were reported in five responders (18%; 95% CI: 7.9-36%) and two non-responders (11%; 95% CI: 2.9-31%), with no statistical difference (p = 0.685). One patient in each arm died after surgery, leading to a postoperative in-hospital mortality rate of 4.3% (2/47 patients; 95% CI: 1.2-14%). CONCLUSION: Local and central FDG-SUV quantification and PET-response assessment showed high concordance. This confirms the accuracy of a PET-response-guided treatment algorithm for locally advanced oesophago-gastric junction cancer in a multicenter setting. Preoperative treatment adaptation revealed feasible and safe for patients.

3rd Department of Surgery 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute Zluty kopec 7 656 53 Brno Czech Republic

Department of Gastroenterology Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Laboratory Medicine Clinical Microbiology and Immunology University Hospital Brno Brno Czech Republic

Department of Nuclear Medicine Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Oncology 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Department of Oncology University Hospital Olomouc Olomouc Czech Republic

Department of Pathology Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Pharmacology Faculty of Medicine Masaryk University Brno Czech Republic

Department of Radiation Oncology Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Surgery Masaryk Memorial Cancer Institute Brno Czech Republic

Faculty of Medicine Masaryk University Brno Czech Republic

Research Centre for Applied Molecular Oncology Masaryk Memorial Cancer Institute Brno Czech Republic

Zobrazit více v PubMed

Bray F, Ferlay J, Soerjomataram I, et al.. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394–424. PubMed

Lordick F, Mariette C, Haustermans K, et al.. Oesophageal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2016; 27: v50–v57. PubMed

Cunningham D, Allum WH, Stenning SP, et al.. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006; 355: 11–20. PubMed

Ychou M, Boige V, Pignon JP, et al.. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 2011; 29: 1715–1721. PubMed

Al-Batran SE, Homann N, Pauligk C, et al.. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet 2019; 393: 1948–1957. PubMed

van Hagen P, Hulshof MCCM, van Lanschot JJB, et al.. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 2012; 366: 2074–2084. PubMed

Ott K, Weber WA, Lordick F, et al.. Metabolic imaging predicts response, survival, and recurrence in adenocarcinomas of the esophagogastric junction. J Clin Oncol 2006; 24: 4692–4698. PubMed

Lordick F, Ott K, Krause BJ, et al.. PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial. Lancet Oncol 2007; 8: 797–805. PubMed

Zum Büschenfelde CM, Herrmann K, Schuster T, et al.. 18F-FDG PET-guided salvage neoadjuvant radiochemotherapy of adenocarcinoma of the esophagogastric junction: the MUNICON II trial. J Nucl Med 2011; 52: 1189–1196. PubMed

Goodman KA, Hall N, Bekaii-Saab TS, et al.. Survival outcomes from CALGB 80803 (Alliance): a randomized phase II trial of PET scan-directed combined modality therapy for esophageal cancer. J Clin Oncol 2018; 36: 4012–4012. PubMed PMC

Barbour AP, Walpole ET, Mai GT, et al.. Preoperative cisplatin, fluorouracil, and docetaxel with or without radiotherapy after poor early response to cisplatin and fluorouracil for resectable oesophageal adenocarcinoma (AGITG DOCTOR): results from a multicentre, randomised controlled phase II trial. Ann Oncol 2020; 31: 236–245. PubMed

Harustiak T, Zemanova M, Fencl P, et al.. [18 F]Fluorodeoxyglucose PET/CT and prediction of histopathological response to neoadjuvant chemotherapy for adenocarcinoma of the oesophagus and oesophagogastric junction. Br J Surg 2018; 105: 419–428. PubMed

Goodman KA, Ou F-S, Hall NC, et al.. Randomized phase II study of pet response–adapted combined modality therapy for esophageal cancer: mature results of the CALGB 80803 (Alliance) trial. J Clin Oncol 2021; 39: 2803–2815. PubMed PMC

Boellaard R, O’Doherty MJ, Weber WA, et al.. FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0. Eur J Nucl Med Mol Imaging 2010; 37: 181–200. PubMed PMC

Karstens KF, Izbicki JR, Reeh M. Does the margin matter in esophageal cancer. Dig Surg 2018; 35: 196–203. PubMed

Mandard A-M, Dalibard F, Mandard J-C, et al.. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer 1994; 73: 2680–2686. PubMed

R Core Team. A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing, 2020, https://www.r-project.org

Kelly RJ, Ajani JA, Kuzdzal J, et al.. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. N Engl J Med 2021; 384: 1191–1203. PubMed

Tepper J, Krasna MJ, Niedzwiecki D, et al.. 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: 1086–1092. PubMed PMC

Urba SG, Orringer MB, Turrisi A, et al.. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol 2001; 19: 305–313. PubMed

Leichman LP, Goldman BH, Bohanes PO, et al.. S0356: a phase II clinical and prospective molecular trial with oxaliplatin, fluorouracil, and external-beam radiation therapy before surgery for patients with esophageal adenocarcinoma. J Clin Oncol 2011; 29: 4555–4560. PubMed PMC

Smyth E, Knödler M, Giraut A, et al.. VESTIGE: adjuvant immunotherapy in patients with resected esophageal, gastroesophageal junction and gastric cancer following preoperative chemotherapy with high risk for recurrence (N+ and/or R1): an open label randomized controlled phase-2-study. Front Oncol 2020; 9: 1320. PubMed PMC

Atay-Rosenthal S, Wahl RL, Fishman EK. PET/CT findings in gastric cancer: potential advantages and current limitations. Imaging Med 2012; 4: 241–250.

Mochiki E, Kuwano H, Katoh H, et al.. Evaluation of 18F-2-deoxy-2-fluoro-d-glucose positron emission tomography for gastric cancer. World J Surg 2004; 28: 247–253. PubMed

De Potter T, Flamen P, Van Cutsem E, et al.. Whole-body PET with FDG for the diagnosis of recurrent gastric cancer. Eur J Nucl Med Mol Imaging 2002; 29: 525–529. PubMed

Stahl A, Ott K, Weber W, et al.. FDG PET imaging of locally advanced gastric carcinomas: correlation with endoscopic and histopathological findings. Eur J Nucl Med Mol Imaging 2003; 30: 288–295. PubMed

Herrmann K, Ott K, Buck AK, et al.. Imaging gastric cancer with PET and the radiotracers 18F-FLT and 18F-FDG: a comparative analysis. J Nucl Med 2007; 48: 1945–1950. PubMed

Ott K, Herrmann K, Lordick F, et al.. Early metabolic response evaluation by fluorine-18 fluorodeoxyglucose positron emission tomography allows in vivo testing of chemosensitivity in gastric cancer: long-term results of a prospective study. Clin Cancer Res 2008; 14: 2012–2018. PubMed

Smyth EC, Verheij M, Allum W, et al.. Gastric cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2016; 27: v38–v49. PubMed

Reynolds JV, Preston SR, O’Neill B, et al.. Neo-AEGIS (Neoadjuvant trial in Adenocarcinoma of the Esophagus and Esophago-Gastric Junction International Study): preliminary results of phase III RCT of CROSS versus perioperative chemotherapy (modified MAGIC or FLOT protocol). (NCT01726452). J Clin Oncol 2021; 39: 4004–4004. PubMed

Hoeppner J, Lordick F, Brunner T, et al.. ESOPEC: prospective randomized controlled multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (NCT02509286). BMC Cancer 2016; 16: 503. PubMed PMC

Leong T, Smithers BM, Haustermans K, et al.. TOPGEAR: a randomized, phase III trial of perioperative ECF chemotherapy with or without preoperative chemoradiation for resectable gastric cancer: interim results from an international, intergroup trial of the AGITG, TROG, EORTC and CCTG. Ann Surg Oncol 2017; 24: 2252–2258. PubMed

Klevebro F, Alexandersson von Döbeln G, Wang N, et al.. A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction. Ann Oncol 2016; 27: 660–667. PubMed

Kwee RM, Marcus C, Sheikhbahaei S, et al.. PET with fluorodeoxyglucose F 18/computed tomography in the clinical management and patient outcomes of esophageal cancer. PET Clin 2015; 10: 197–205. PubMed

Lorenzen S, Quante M, Rauscher I, et al.. PET-directed combined modality therapy for gastroesophageal junction cancer: first results of the prospective MEMORI trial. J Clin Oncol 2019; 37: 4018–4018. PubMed