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

Abstract

Purpose:We prospectively evaluated the predictive value of positron emission tomography using fluorine-18 fluorodeoxyglucose (FDG-PET) for in vivo testing of chemosensitivity in locally advanced gastric cancer using an a priori definition of metabolic response (a decrease of >35% of the standarduptake value).The goalof the study was the definitionof biologically differentgroups of patients prior to or early during induction therapy, with special emphasis on FDGnon^avid tumors. Experimental Design: Based on our data, which was published in 2003, at least 36 patients with metabolic response or FDG non^avid tumors had to be recruited for an analysis of the group of FDG non^avid tumors with sufficient statistical power. Seventy-one patients (32 metabolic nonresponders, 17 metabolic responders, and 22 patients with FDG non^avid tumors) underwent FDG-PET at baseline. In FDG-avid tumors, FDG-PET was repeated 14 days after the initiation of chemotherapy. Results: Metabolic responders (17 of 49) showed a high histopathologic response rate (69%) and a favorable prognosis (median survival not reached), whereas metabolic nonresponders (32 of 49) had a poor prognosis (median survival, 24.1 months) and showed a histopathologic response in 17%. The histopathologic response rate (24%) for FDG-PET non^avid patients showed no significant difference compared with FDG-avid nonresponders (P = 0.72). Survival of FDG non^avid patients was 36.7 months (not significantly different from FDG-avid nonresponders, 24.1months, P = 0.46). Conclusion: In locally advanced gastric cancer, three different metabolic groups exist. Response and survival was predicted by PET in FDG-avid tumors. Metabolic response assessment was not possible in FDG non^avid tumors; however, due to unfavorable outcome, therapy modification might also be considered in FDG non^avid tumors.Recently, a randomized phase III study in patients with operable gastric or lower esophageal adenocarcinoma was published by Cunningham et al., demonstrating improved overall and progression-free survival following perioperative chemotherapy compared with surgery alone (1).However, only 30% to 40% of patients showed a measurable clinical or histopathologic response after neoadjuvant treatment (2 -6). Therefore, it would be important to identify patients who do not respond to chemotherapy early in the course of treatment, or even prior to treatment, in order to avoid ineffective therapy with its associated side effects and costs.Current imaging modalities or molecular markers cannot reliably predict therapy response prior to or early in the course of the treatment-the time when this information is most important (7,8). In contrast, positron emission tomography (PET) imaging after 2 weeks of chemotherapy is significantly correlated with histopathologic regression and prognosis in patients with adenocarcinoma of the esophagogastric junction (AEG) I and II (5, 6). Interestingly, approximately one third of patients with gastric cancer, even with locally advanced tumors, initially hav...

Japanese Gastric Cancer Association Task Force for Research Promotion: clinical utility of 18F-fluoro-2-deoxyglucose positron emission tomography in gastric cancer. A systematic review of the literature

“…They classified the tumors that demonstrated more than 35% reduction of FDG uptake as a responder group and the tumors that demonstrated less than 35% reduction of FDG uptake as non-responders. For these PET responders, ''metabolic responders'', the treatment should be continued, and for non-responders another treatment strategy should be employed [44]. On the other hand, PET reassessment after the completion of neoadjuvant chemotherapy did not detect significant correlations between the SUVs of the major and minor responder groups [45].…”

“…However, FDG also accumulates in inflammatory cells, and false-positive findings are found in the inflammatory stage after treatment. Considering these characteristics of PET, the usefulness of early response evaluation after the initiation of the treatment has been reported by several institutions [40][41][42][43][44]. The ideal examination times and criteria have not been determined [41].…”

“…The ideal examination times and criteria have not been determined [41]. Ott et al [43,44] reported that the best evaluation time was 2 weeks after the initiation of treatment. They classified the tumors that demonstrated more than 35% reduction of FDG uptake as a responder group and the tumors that demonstrated less than 35% reduction of FDG uptake as non-responders.…”

Gastric cancers with microsatellite instability exhibit high fluorodeoxyglucose uptake on positron emission tomography

“…FDG-PET/CT imaging is expected to provide more precise anatomical data in addition to metabolic information. For gastric cancers, FDG-PET imaging provides important additional information concerning the prognosis of recurrent cancer, including lymph node metastases, peritoneal carcinomatosis, distant metastasis, tumor response to treatment, and overall survival [3][4][5][6][7][8][9][10]. However, some subtypes of gastric cancer exhibit reduced FDG uptake [3,[11][12][13][14], which significantly limits the use of PET in gastric cancer.…”

The higher the decrease in the standardized uptake value of positron emission tomography after chemoradiation, the better the survival of patients with gastroesophageal adenocarcinoma

“…[15][16][17][18] However, the initial results and subsequent changes in positron emission tomography (PET) show promise. [19][20][21][22][23][24][25] Many investigators have demonstrated that decrease in metabolic activity as measured by the standardized uptake value (SUV) on PET/computed tomography (CT) as a result of therapy is of prognostic value. [25][26][27][28] In addition, PET/CT images obtained during therapy have been studied in a limited number of patients and seem to provide useful information regarding the response to therapy and prognosis of patients.…”