From the 141 patients operated in the study period, 89 had a baseline 18F- FDG PET/CT in their workup (63%). Three of them were excluded from analysis because of histology other than adenocarcinoma or squamous cell; thus, the current series consists of 86 patients. Baseline patient characteristics are outlined in Table 1. Adenocarcinoma represented 53% and squamous cell histology 47% of all lesions; 94% of all tumors were FDG-avid in 18F- FDG PET/CT.
Baseline 18F- FDG PET/CT -derived parameters and initial tumor staging
a) SUVmax (maximal Standardized Uptake Value)
Median baseline SUVmax was 12.1 g/mL (range 2.8-48.0) for all tumors. Middle third tumor location, advanced cT and cN stage as well as squamous cell histology were associated with higher SUVmax values on a univariate level, however only tumor location and cT stage remained significant on multiple regression (Table 2). cT3/4 tumors had an expected SUVmax 6.61 higher than a cT1-2 lesion (β coefficient 6.61, 95%CI 2.40, 10.81, p=0.002), and middle third tumors an expected SUVmax 7.01 higher than GEJ lesions (β coefficient 7.01, 95%CI 0.71-13.32, p=0.029). The multivariable model presented a good fit to the data (R2= 0.2804, F-statistic 4.676 on 6 and 72 DF, p<0.0001).
Baseline SUVmax presented a good prognostic value of a cT3/4 status in ROC curve analysis (Figure 1a). A SUVmax > 8.25g/mL predicted a cT3/4 lesion with a sensitivity of 84% and a specificity of 68%. Overall accuracy as indicated by the area under the curve (AUC) was 82% (AUC=0.816, 95%CI=0.704-0.928, p<0.001).
b) TLG (Total Lesion Glycolysis)
in multivariate analysis; expected TLG for cT3/4 tumors was 162.9 higher than cT1/2 tumors (β coefficient 162.95, 95% CI 31.39-294.51, p=0.016), and cN+ had a TLG 145.83 higher than cN0 lesions (β coefficient 145.83, 95% 34.47-256.19, p=0.010). (Table 3) The model presented a good fit to the data (R2= 0.1852, F-statistic 7.841 on 2 and 69DF, p<0.001).
ROC curve analysis identified a TLG >41.7 g as the optimal cutoff to detect a cT3/4 lesion, with a sensitivity of 86%, a specificity of 80% and an overall accuracy of 85% (AUC 0.852, 95%CI 0.744-0.960, p<0.001) (Figure 1b)
c) MTV (Metabolic Tumor Volume)
Median MTV for all FDG-avid tumors was 22.7 cm3 (range 1-519). Univariate analysis identified only active smoking being associated with higher baseline MTV (β coefficient 32.81, 95%CI 4.99-70.62, p=0.093) and thus, no multivariable analysis was possible for this parameter.
In ROC curve analysis a baseline MTV> 10.70 cm3 was identified as the optimal cutoff to predict cT3/4 status (sensitivity 83.1%; specificity 75%, AUC 0.799, 95%CI 0.640-0.959, p=0.01) (Figure 1c).
Prognostic value of 18F- FDG PET/CT -derived parameters for recurrence and patient survival
Among the three parameters studied, SUVmax at baseline was the only one with a significant predictive value for early tumor recurrence, within the 1st postoperative year (Figure 2). A SUVmax > 12.7g/mL predicted early recurrence with 70.4% sensitivity and 64.6% specificity (AUC 0.660, 95% CI 0.535-0.785, p=0.019) (Figure 2a). Patients with a SUVmax ≤ 12.7 g/mL at baseline had a median disease-free survival (DFS) of 56 months (95%CI 7.7-104), versus 13 (95%CI 10.4-15.7) for those with a SUVmax > 12.7g/mL (p=0.030) (Figure 3). Cox regression confirmed SUVmax > 12.7g/mL as an independent predictor of DFS (HR 2.54, 95%CI 1.26, 5.09, p=0.009), along with preoperative active smoking and pT3/4 status (Table 4).
When the two histological subtypes were analyzed separately, there was no significant association of SUVmax with DFS for adenocarcinoma. For squamous cell carcinoma, a baseline SUVmax > 12.7g/mL along with pT and pN stage independently predicted worse DFS (Table 4). The distinct metabolic profile of the two histological types is illustrated in Figure 4.
No association was found between baseline SUVmax and overall survival (OS), neither on the Kaplan-Meier (Figure 3) nor the Cox regression analysis. In the latter, only active smoking (HR 2.30, 95% CI 1.15-4.62, p=0.019) and pT4 stage (HR 21.42, 95%CI 5.00- 91.72, p<0.0001) independently predicted OS. None of the variables remained independent predictors of OS in adenocarcinoma or squamous cell subtypes.
Median follow-up of all patients, calculated with the reverse Kaplan-Meier method, was 50 months (95%CI 45.33-54.66).