The asphericity of the metabolic tumour volume in NSCLC: correlation with histopathology and molecular markers

PURPOSE: Asphericity (ASP) is a tumour shape descriptor based on the PET image. It quantitates the deviation from spherical of the shape of the metabolic tumour volume (MTV). In order to identify its biological correlates, we investigated the relationship between ASP and clinically relevant histopathological and molecular signatures in non-small-cell lung cancer (NSCLC).

METHODS: The study included 83 consecutive patients (18 women, aged 66.4 ± 8.9 years) with newly diagnosed NSCLC in whom PET/CT with (18)F-FDG had been performed prior to therapy. Primary tumour 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 images of the primary tumours were delineated using an automatic algorithm based on adaptive thresholding taking into account local background. In addition to ASP, SUVmax, MTV and some further descriptors of shape and intratumour heterogeneity were assessed as semiquantitative PET measures.

RESULTS: SUVmax, MTV and ASP were associated with pathological T stage (Kruskal-Wallis, p = 0.001, p < 0.0005 and p < 0.0005, respectively) and N stage (p = 0.017, p = 0.003 and p = 0.002, respectively). Only ASP was associated with M stage (p = 0.026). SUVmax, MTV and ASP were correlated with Ki-67 index (Spearman's rho = 0.326/p = 0.003, rho = 0.302/p = 0.006 and rho = 0.271/p = 0.015, respectively). The latter correlations were considerably stronger in adenocarcinomas than in squamous cell carcinomas. ASP, but not SUVmax or MTV, showed a tendency for a significant association with the extent of VEGF expression (p = 0.058). In multivariate Cox regression analysis, ASP (p < 0.0005) and the presence of distant metastases (p = 0.023) were significantly associated with progression-free survival. ASP (p = 0.006), the presence of distant metastases (p = 0.010), and Ki-67 index (p = 0.062) were significantly associated with overall survival.

CONCLUSION: The ASP of primary NSCLCs on FDG PET images is associated with tumour dimensions and molecular markers of proliferation and angiogenesis.