1. Introduction
In vivo disease biomarkers are increasingly demanded by clinicians in order to characterize a disease, to make prognosis and to predict response to treatment non invasively.
Body-Weight Standardized Uptake Value (SUVBW), measured by Fluorodeoxyglucose and Positron Emission Tomography (18F-FDG PET), has been extensively used as semi-quantitative index accounting for altered glucose metabolism of an oncological lesion. In order to obtain an accurate measurement of 18F-FDG SUVBW, a Correction for Partial Volume Effect (PVC) has been proved mandatory, since this effect causes severe underestimation of SUVBW (up to 80% - 90% for small lesions) [1,2].
Aim of this work was to evaluate the metabolic impact of PVC on SUVBW as potential in vivo prognostic biomarker of gastric and gastro-oesophageal cancer, reflecting ex vivo histo-pathological characteristics.
2. Materials and Methods
Fourty-nine patients (31 men, 18 women; mean age 63 ± 13 years; age range: 33 - 83 years) with biopsy-proven gastric and gastro-oesophageal cancer underwent a basal 18F-FDG PET-CT study. 18F-FDG PET/CT sensitivity was assessed. Patient weight, and injected/residual dose were measured in order to calculate PVC-SUVBW on primitive gastric and gastro-oesophageal lesions detected on 18F-FDG PET images.
Patients fasted for twelve hours before the exams and were intravenous injected with 18F-FDG (1 mCi/10 kg). The PET-CT protocol began 60 minutes after the injection. All PET-CT studies were performed according to the oncological clinical protocol implemented on the discovery STE scanner, including a SCOUT scan at 40 mA, a CT scan at 140 keV and 150 mA (10 s) and 3D PET scans (2.5 min/scan) for adjacent bed positions. PET images were reconstructed by a 3D ordered subset expectation maximization algorithm (OSEM, 28 subsets, 2 iterations, 5.14 mm Gaussian post-smoothing) with corrections for random, scatter and attenuation incorporated into the iterative process.
An Operator Independent technique using an automatic threshold was used to define Regions of Interest (ROIs) on PET images [2] and quantitative analysis was performed by calculating mean SUVBW for each primitive gastric and gastro-oesophageal lesions. The RC-based correction methods developed in [2] was used to correct in order to account for Partial Volume Effect.
Both SUVBW and PVC-SUVBW were obtained by TouchSUV software [3,4].
Correlation tests (Mann-Whitney and Kruskal Wallis tests for univariate analysis and hierarchical clustering combined with a pre-processing k-means analysis for multivariate analysis) were performed in order to evaluate the relationships between 18F-FDG PVC-SUVBW and biopsy-evaluated histotype (signet ring cell carcinoma (SR), squamous cell carcinoma (S) and other adenocarcinoma (ADK) subtype) and grade (G1, G2, G3) (according to WHO and Lauren classifications).
3. Results
18F-FDG PET/CT was able to detect gastric and gastrooesophageal cancer with a sensitivity of 82%: 18F-FDG PET/CT images of 9 (18%) biopsy-proven gastric cancers were classified as negative, showing no 18F-FDG uptake in the primitive lesions. Negative PET images were not quantified and were excluded by correlation analysis.
Mean primitive lesion diameter (sphere-equivalent diameter) was 2.15 ± 1.17 cm, ranging from 0.99 cm to 6.25 cm. Lesion size confirmed the need of PVC for accurate PET quantification for more than 75% of lesions [2].
Signet ring cell carcinomas showed a lower 18F-FDG PVC-SUVBW compared to squamous cell carcinomas and to other adenocarcinoma subtypes (PVC-SUVBW: 5.57 ± 3.22 g/cc vs 9.90 ± 1.91 g/cc vs 9.32 ± 4.26 g/cc; Mann-Whitney test, p < 0.05). No correlation was found when PVC was not applied to SUVBW.
No correlations were found between grade and 18FFDG PVC-SUVBW or 18F-FDG SUVBW (Kruskal Wallis test, p > 0.05).
Figure 1 shows the results for univariate analysis.
The pre-processing k-means cluster analysis allowed to stratify patients in three different groups on the basis of PVC-SUVBW (PVC-SUVBW ≤ 6.25 g/cc; 6.25g/cc < PVC-SUVBW < 11.60 g/cc; PVC-SUVBW ≥ 11.60 g/cc). Using these groups, the hierarchical cluster analysis performed on PVC-SUVBW, histotype and grade showed that poorly differentiated (G3) signet ring cell carcinomas were significantly associated with 18F-FDG PVCSUVBW ≤ 6.25 g/cc (p < 0.05), while moderately differentiated (G2, G1) squamous cell carcinoma were significantly associated with 18F-FDG PVC-SUVBW > 11.6 g/cc; (p < 0.05).
Figure 2 shows the results of the hierarchical cluster analysis.