The Value of PET Imaging in Patients with Localized Gastroesophageal Cancer

摘要

Preoperative induction therapy in stages II and III adenocarcinoma of the esophagogastric junction (AEG) and gastric cancer is now an accepted treatment choice in the Western world. Patients who respond to induction therapy have significantly improved survival compared to nonresponding patients. Until recently, however, no prospectively tested markers for predicting response and/or prognosis in this settingwere available. The MUNICON I study recently showed the utility of fluorodeoxyglucose-positron emission tomography (FDG-PET) in predicting response and prognosis in AEG and indicated the feasibility of a PET-guided treatment algorithm. These findings are an important step forward in tailoring multimodal treatment to tumor biology. In gastric cancer, the issue is more complicated, because approximately 30% of these cancers cannot be visualized with sufficient contrast for quantification. Insufficient FDG uptake is mostly associated with diffusetype gastric cancer with signet cells and mucinous content. In FDG avid patients, FDG-PET can be used for response evaluation. The prognosis of nonavid patients is similar to metabolic nonresponders. The addition of new tracers (eg, fluorothymidine) might increase the accuracy of these tests in the future. In AEG types I and II, PET-guided induction therapy is feasible and will undergo further evaluation in a randomized multicenter trial. In gastric cancer, there should be consideration of such treatment concepts as immediate resection after 2 weeks of induction therapy with or without adjuvant treatment in metabolic nonresponders or modified chemotherapy regimens possibly including biologically targeted drugs in FDG non-avid tumors. After the publication of three randomized controlled trials showing benefit, neoadjuvant chemotherapy has become an accepted choice for the treatment of locally advanced adenocarcinomas of the esophagus and the esophagogastric junction (AEG) and gastric cancer. 1 – 3 The use of neoadjuvant chemotherapy without the addition of radiotherapy is not generally accepted for AEG type I. In many institutions, concurrent or sequential radiotherapy is delivered, but a recent meta-analysis provides justification for both the neoadjuvant chemotherapy and chemoradiotherapy approach in the treatment of resectable adenocarcinomas of the esophagus. 4 However, there is also some evidence that the addition of radiation therapy might increase the risk of postoperative morbidity and mortality compared to chemotherapy alone, which may be due to immunosuppression associated with radiation therapy. 5 , 6 Due to these facts, neoadjuvant chemotherapy has been the treatment of choice for locally advanced esophageal adenocarcinomas in the authors’ and others’ institutions. The potential benefits of giving chemotherapy before surgery are downsizing and downstaging of the primary tumor and lymph node metastases, early treatment of micrometastases, increased rates of curative resections, and improved tumor-related symptoms. A newer potential advantage is the possibility of testing in vivo the chemosensitivity of the primary tumor, which may influence choice of chemotherapy in the adjuvant setting. The feasibility of neoadjuvant treatment in locally advanced gastric cancer has been shown in numerous phase II studies with different regimens. 7 – 10 Compared to historical controls, prognosis of patients receiving neoadjuvant treatment seems to be improved and toxicity has been moderate in most studies. 8 , 11 Treatment acceptance and compliance have been high and treatment has been well tolerated, with nearly all patients being able to receive the complete neoadjuvant dose. In adenocarcinomas of the distal esophagus, an abdominothoracic approach and reconstruction with a small gastric tube interposition in the posterior mediastinum with intrathoracic anastomosis (Ivor-Lewis operation) including a two-field lymphadenectomy has become the procedure of choice. 12 In Europe, an abdominal D2 lymphadenectomy is performed at most centers with extensive experience with gastric cancer and (in contrast to US centers) postoperative chemoradiotherapy is not a standard of care. 13 – 15