Relationship between asphericity of FDG uptake in the primary tumor and prognostic molecular signatures in NSCLC

Ziel/Aim:

Asphericity (ASP) is a novel FDG-PET-based tumor heterogeneity measure which quantitatively characterizes the deviation of the tumor’s metabolic volume from sphere shape. In order to understand its biological correlates we investigated the relationship with molecular signatures known to be prognostic in NSCLC.

Methodik/Methods:

The study included 84 consecutive patients (18 females, 66.4±8.8 years) with newly diagnosed NSCLC in whom FDG-PET/CT had been performed prior to therapy. Primary tumor resection specimens and core biopsies were used for basic histopathology and determination of the Ki-67 proliferation index. EGFR status, VEGF, p53 and ALK expression were obtained in a subgroup of 44 patients. The FDG PET image of the primary tumor was delineated by an automatic algorithm based on adaptive thresholding accounting for local background. ASP and SUVmax were considered as quantitative PET measures.

Ergebnisse/Results:

Ki-67 correlated with SUVmax (Spearman rho=0.325, p=0.002) as well as with ASP (rho=0.232, p=0.018). Both correlations were considerably stronger in adenocarcinomas than in squamous cell carcinomas. Multivariate logistic regression of Ki-67 included only ASP. Neither SUVmax nor ASP correlated with p53. ASP but not SUVmax was associated with VEGF (AUC=0.789, p=0.024) and showed a tendency towards association with EGFR positivity (AUC=0.722, p=0.065). All tumors were ALK negative. Univariate Cox regression revealed progression free survival (PFS) to be associated with stage (p=0.004) and ASP (p<0.001). Overall survival (OS) was associated with stage (p=0.001), Ki-67 (p=0.008), and ASP (p<0.001). Multivariate Cox regression included ASP (p=0.001) and stage (p=0.044) for PFS, but only ASP (p=0.015) for OS.

Schlussfolgerungen/Conclusions:

Molecular signatures of proliferation and angiogenesis seem to contribute to asphericity of primary lung tumors.