title: PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial.
abstract: BACKGROUND
  In patients with locally advanced adenocarcinoma of the oesophagogastric junction (AEG), early metabolic response defined by 18-fluorodeoxyglucose-PET ([(18)F]FDG-PET) during neoadjuvant chemotherapy is predictive of histopathological response and survival. We aimed to assess the feasibility of a PET-response-guided treatment algorithm and its potential effect on prognosis.
  
  
  METHODS
  Between May 27, 2002, and Aug 4, 2005, 119 patients with locally advanced adenocarcinoma of AEG type 1 (distal oesophageal adenocarcinoma) or type 2 (gastric cardia adenocarcinoma) were recruited into this prospective, single-centre study. All patients were assigned to 2 weeks of platinum and fluorouracil-based induction chemotherapy (evaluation period). Those with decreases in tumour glucose standard uptake values (SUVs), predefined as decreases of 35% or more at the end of the evaluation period and measured by PET, were defined as metabolic responders. Responders continued to receive neoadjuvant chemotherapy of folinic acid and fluorouracil plus cisplatin, or folinic acid and fluorouracil plus cisplatin and paclitaxel, or folinic acid and fluorouracil plus oxaliplatin for 12 weeks and then proceeded to surgery. Metabolic non-responders discontinued chemotherapy after the 2-week evaluation period and proceeded to surgery. The primary endpoint was median overall survival of metabolic responders and non-responders. Secondary endpoints were median event-free survival, postoperative complications and mortality, number of residual tumour-free (R0) resections, and histopathological responses. This study has been registered in the European Clinical Trials Database (EudraCT) as trial 2007-003356-11.
  
  
  RESULTS
  110 patients were evaluable for metabolic responses. 54 of these patients had metabolic responses (ie, decrease of 35% or more in tumour glucose SUV) after 2 weeks of induction chemotherapy, corresponding to a response of 49% (95% CI 39-59). 104 patients had tumour resection (50 in the responder group and 54 in the non-responder group). After a median follow-up of 2.3 years (IQR 1.7-3.0), median overall survival was not reached in metabolic responders, whereas median overall survival was 25.8 months (19.4-32.2) in non-responders (HR 2.13 [1.14-3.99, p=0.015). Median event-free survival was 29.7 months (95% CI 23.6-35.7) in metabolic responders and 14.1 months (7.5-20.6) in non-responders (hazard ratio [HR] 2.18 [1.32-3.62], p=0.002). Major histological remissions (<10% residual tumour) were noted in 29 of 50 metabolic responders (58% [95% CI 48-67]), but no histological response was noted in metabolic non-responders.
  
  
  CONCLUSIONS
  This study confirmed prospectively the usefulness of early metabolic response evaluation, and shows the feasibility of a PET-guided treatment algorithm. These findings might enable tailoring of multimodal treatment in accordance with individual tumour biology in future randomised trials.
authors: Department of Surgery, Clinic rechts der Isar, Technical University of Munich, Munich, Germany. florian.lordick@med.uni-heidelberg.de
authors: Florian
authors: F
authors: Lordick
authors: Katja
authors: K
authors: Ott
authors: Bernd-Joachim
authors: BJ
authors: Krause
authors: Wolfgang A
authors: WA
authors: Weber
authors: Karen
authors: K
authors: Becker
authors: Hubert J
authors: HJ
authors: Stein
authors: Sylvie
authors: S
authors: Lorenzen
authors: Tibor
authors: T
authors: Schuster
authors: Hinrich
authors: H
authors: Wieder
authors: Ken
authors: K
authors: Herrmann
authors: Rainer
authors: R
authors: Bredenkamp
authors: Heinz
authors: H
authors: Höfler
authors: Ulrich
authors: U
authors: Fink
authors: Christian
authors: C
authors: Peschel
authors: Markus
authors: M
authors: Schwaiger
authors: Jörg R
authors: JR
authors: Siewert
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000628:therapy*; D000368:Aged; D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000000981:diagnostic imaging* / Q000628:therapy*; D004943:Esophagogastric Junction; D005240:Feasibility Studies; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D049268:Positron-Emission Tomography; D011379:Prognosis; D015996:Survival Rate
chemical_list: D019788:Fluorodeoxyglucose F18