Abstract
Simple SummaryThe diffuse type of gastric adenocarcinoma (dGAC) generally confers a poor prognosis compared to intestinal type. Some dGACs are not avid on fluorine-18 fluoro-2-deoxy-D-glucose PET (FDG-PET) while others seem to consume glucose avidly. We analyzed the outcomes based on the avidity of the primary on baseline FDG-PET. Our data suggest that if dGACs used glucose as an energy source then the prognosis was very poor while non-glucose sources improved prognosis. Multi-platform (including metabolomics) profiling of dGACs would yield useful biologic understanding.Diffuse type of gastric adenocarcinoma (dGAC) generally confers a poor prognosis compared to intestinal type. Some dGACs are not avid on fluorine-18 fluoro-2-deoxy-D-glucose PET (FDG-PET) while others seem to consume glucose avidly. We analyzed the outcomes based on the avidity (high with standardized uptake value (SUV) > 3.5 or low with SUV ≤ 3.5) of the primary on baseline FDG-PET. We retrospectively selected 111 localized dGAC patients who had baseline FDG-PET (all were treated with preoperative chemotherapy and chemoradiation). FDG-PET avidity was compared with overall survival (OS) and response to therapy. The mean age was 59.4 years and with many females (47.7%). The high-SUV group (58 (52.3%) patients) and the low-SUV group (53 (47.7%) patients) were equally divided. While the median OS for all patients was 49.5 months (95% CI: 38.5–98.8 months), it was 98.0 months (95% CI: 49.5–NE months) for the low-SUV group and 36.0 months for the high-SUV (p = 0.003). While the median DFS for all patients was 38.2 months (95% CI: 27.7–97.6 months), it was 98.0 (95% CI: 36.9–NE months) months for the low-SUV group was and only 27.0 months (95% CI: 15.2–63.2 months) for the high-SUV group (p = 0.005). Clinical responses before surgery were more common in the low-SUV group but overall we observed only 4 pathologic complete responses in 111 patients. Our unique data suggest that if dGACs used glucose as an energy source then the prognosis was very poor while non-glucose sources improved prognosis. Multi-platform (including metabolomics) profiling of dGACs would yield useful biologic understanding.
Highlights
Gastric adenocarcinoma (GAC) is the third leading cause of cancer-related deaths and ranks as the fifth most common cancer worldwide [1]
GAC represents 95% of all types of gastric cancers and is divided into two major subtypes: intestinal type and diffuse type with or without signet ring cells (SRCs) [2,3]. Diffuse type of gastric adenocarcinoma (dGAC) was relatively less frequently seen (32%) in the past compared to iGAC (54%) but its incidence has been rising alarmingly [4]
It is more frequently seen in females, younger individuals, and Blacks [4,5]. dGAC lacks the intercellular adhesion molecules and GAC cells do not form glands and often are dispersed as single cells or small clusters surrounded by fibrous stroma [4]
Summary
Gastric adenocarcinoma (GAC) is the third leading cause of cancer-related deaths and ranks as the fifth most common cancer worldwide [1]. GAC represents 95% of all types of gastric cancers and is divided into two major subtypes: intestinal type (iGAC) and diffuse type (dGAC) with or without signet ring cells (SRCs) [2,3]. FDG-PET/CT may be useful in differentiating dGAC subtypes [19] as the prognosis of dGAC patients is varied. The potentially low FDG avidity in dGAC is attributed to several factors, including the low-density diffuse infiltration of GAC cells, existence of extracellular or intracellular metabolically inert mucus content, use of glutamine as fuel rather than glucose, and low expression level of glucose transporter 1 (GLUT-1) [20,21]. We assessed the correlation between FDG-PET/CT avidity at baseline (prior to any treatment) and survival of preoperatively treated dGAC patients
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