Optimizing neoadjuvant chemotherapy through the use of early response evaluation by positron emission tomography.

Metabolic imaging and early response assessment by positron emission tomography (PET) may guide treatment of localized esophageal cancers. The most consistent and validated results have been obtained during neoadjuvant treatment of adenocarcinoma of the esophago-gastric junction (AEG). It was demonstrated that 18F-Fluorodeoxyglucoe (FDG)-PET is highly accurate for identifying non-responding tumors within 2 weeks after the initiation of neoadjuvant chemotherapy when a quantitative threshold for metabolic response is used. In consecutive phase II studies the metabolic activity, defined by the standardized uptake (SUV) of 18-FDG before and during chemotherapy, was measured. Significant decreases of the SUV after only two weeks of induction chemotherapy were observed. A drop of >35 % 2 weeks after the start of chemotherapy revealed as an accurate cut-off value to predict response after a 12-week course of preoperative chemotherapy. This cut-off was recently confirmed in a US study, where investigators did follow-up PET not 14 days but 6 weeks after initiation of chemotherapy. It was further noticed that the metabolic response to induction chemotherapy revealed as an independent prognostic factor in locally advanced AEG. Therefore, PET could be used to tailor treatment according to the sensitivity of an individual tumor. This concept was realized in the MUNICON-1 and -2 trials. These trials prospectively confirmed that responders to induction chemotherapy can be identified by early metabolic imaging using FDG-PET. Continuing neoadjuvant chemotherapy in the responding population resulted in a favorable outcome. Moreover, MUNICON-1 showed that chemotherapy can be discontinued at an early stage in metabolic non-responders without compromising the patients' prognosis, but saving time and reducing side effects and costs. MUNICON-2 showed that the addition of neoadjuvant radiation therapy in metabolic nonresponders did not lead to an improvement of their poor prognosis, thus showing that early metabolic nonresponse indicates dismal tumor biology. Future studies need to validate the prognostic and predictive value of PET in multicenter settings and in conjunction with different neoadjuvant chemotherapy and chemo-immunotherapy regimens.