Fast track — ArticlesPET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial
Introduction
After the publication of two randomised controlled trials,1, 2, 3 neoadjuvant chemotherapy has become an accepted choice for the treatment of locally advanced adenocarcinoma of the oesophagus and the oesophagogastric junction. However, for patients who do not respond, the prognosis after neoadjuvant chemotherapy might be worse than that of a primarily surgical approach.4 Additionally, inefficient neoadjuvant treatment leads to adverse events, allows tumour progression during chemotherapy, costs time, and increases health expenses. Therefore, the ability to predict response to chemotherapy is clearly desirable.
Measurement of early changes in tumour glucose uptake by use of 18-fluorodeoxyglucose-PET ([18F]FDG-PET) has yielded reproducible results that are useful for predicting clinical and histopathological response after multiple-course neoadjuvant chemotherapy.5, 6 Specifically, we have noted that when a quantitative threshold for metabolic response is used, PET identifies accurately non-responding tumours within 2 weeks of treatment initiation. This finding suggests that PET can be used to tailor treatment to individual patients.
Studies that show the use of PET results for modifying treatment are currently absent, despite the promising findings of studies evaluating PET for monitoring tumour response during treatment.7 By contrast to previous studies from our institution that assessed and validated the optimum cut-off values for the early prediction of response,5, 6 the study presented here (the Metabolic response evalUatioN for Individualisation of neoadjuvant Chemotherapy in oesOphageal and oesophagogastric adeNocarcinoma (MUNICON) trial prospectively evaluated the feasibility and potential effect on prognosis of administering PET-response-guided chemotherapy to patients with locally advanced adenocarcinoma of the oesophagus and the oesophagogastric junction.
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Patients
Patients with locally advanced adenocarcinoma of the oesophagogastric junction (AEG) type 1 (distal oesophageal adenocarcinoma) or type 2 (gastric cardia adenocarcinoma) according to Siewert's classification8) were eligible. Patients were staged as cT3 or cT4 based on CT and endoscopic ultrasonography. Haematogenous metastases were excluded by PET. Exclusion criteria were: medical contraindications against chemotherapy with platinum plus fluorouracil; or unacceptable risks for oesophagectomy,
Results
Between May 27, 2002, and Aug 4, 2005, 119 consecutive patients (eight women and 111 men) were enrolled in the study. Eight of these patients were excluded because they did not meet the inclusion criteria—protocol violations were identified by one of the leading investigators (FL, KO, or JRS) within 1 week and led to exclusion from further study treatment and analysis: three patients did not have AEG type 1 or 2, but had subcardiac gastric cancer; two had haematogenous metastases; two had an
Discussion
Our study confirms that early metabolic response measured by PET identifies patients with locally advanced adenocarcinomas of the distal oesophagus and gastric cardia (AEG type 1 and AEG type 2) who have a high chance of achieving major histological responses after neoadjuvant chemotherapy, and therefore, have a favourable prognosis. The study also shows the feasibility of a PET-response-guided treatment algorithm in the management of such tumours.
Individualised, response-guided treatment
References (43)
- et al.
Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis
Lancet Oncol
(2007) - et al.
Pathology of upper gastrointestinal malignancies
Semin Oncol
(2004) - et al.
Positron emission tomography for assessment of the response to induction radiochemotherapy in locally advanced oesophageal cancer
Ann Oncol
(2002) - et al.
Utility of PET, CT, and EUS to identify pathologic responders in esophageal cancer
Ann Thorac Surg
(2004) Cancer of the gastroesophageal junction: combined modality therapy
Surg Oncol Clin N Am
(2006)- et al.
Salvage esophagectomy for recurrent tumors after definitive chemotherapy and radiotherapy
J Thorac Cardiovasc Surg
(2002) - et al.
Therapeutic strategies in oesophageal carcinoma: role of surgery and other modalities
Lancet Oncol
(2007) - et al.
Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer
N Engl J Med
(2006) Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial
Lancet
(2002)- et al.
Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer
N Engl J Med
(1998)