Prognostic role of quantitative [18F]FDG PET/CT parameters in adrenocortical carcinoma

Abstract

Purpose: We aimed to evaluate the prognostic potential of baseline [¹⁸F]FDG PET/CT for overall survival (OS) in patients with adrenocortical carcinoma (ACC).

Methods: We performed a retrospective analysis of 67 treatment-naïve ACC patients with available [¹⁸F]FDG PET/CT at time of initial diagnosis. Pretherapeutic PETs of primary tumors were manually segmented and quantitative parameters (maximum/mean/peak standardized uptake value (SUV_{max/mean/peak}), metabolic tumor volume (MTV) and tumor lesion glycolysis (TLG, defined as TV*SUV_mean) were derived. Based on a visual read, absence (M0) or presence of metastatic disease (M1) were evaluated. Kaplan-Meier and Cox regression analyses were used to determine the prognostic value of the above mentioned markers on overall survival adjusted for established prognostic markers.

Results: 24/67 patients (36%) presented with M0 based on PET/CT, while the remaining 43/67 (64%) had M1-status. 32/67 patients died during follow-up and median OS was 48 months. In 12% of patients FDG-PET detected additional metastatic lesion not clearly visible by CT only. In univariable analysis, all quantitatively derived PET parameters failed to reach significance (P ≥ 0.1), and only PET/CT-based M1-status and Ki-67 were associated with increased mortality (M1: HR 13.89, 95% CI 4.15-86.32, P < 0.001; Ki-67 HR 1.29, 95% CI 1.16-1.42; P < 0.0001). Using multivariable Cox regression analyses, M1-status (HR 9.69, 95% CI 2.82-60.99) and Ki-67 index (HR 1.29, 95% CI 1.13-1.04; P < 0.05) remained significant associated with OS.

Conclusion: In treatment-naïve ACC patients, the quantitative PET parameter failed to predict OS, but presence of metastases detected by [¹⁸F]FDG PET/CT and Ki-67 index were independently associated with shorter OS. Therefore, a simple visual PET-based read-out is of prognostic value at initial diagnosis, while time-consuming PET-based quantification can be omitted.

Keywords: ACC; Endocrine; SUVmax; Survival; Treatment-naïve.

Fig. 1

Example of segmentation of the primary tumor. An isocontour volume of interest (VOI) using a threshold SUV of 3.0 was drawn using a three-dimensional segmentation method allowing for a semi-automatic volumetric assessment (measurement results of the patient example: SUV_max 12.3. SUV_peak 9.08. SUV_mean 5.24. TLG 1737.03. MTV 331.68)

Fig. 2

Kaplan–Meier plots for probability of progression free and overall survival (PFS/OS) using SUV_max, TBR and Ki-67 index, as well as presence of metastatic disease (M1) based on [¹⁸F]FDG PET/CT and number of organ compartments affected by metastases. In this regard, two or more affected organ compartments (M1-2) exhibited shortest survival relative to M1-1, defined as only one affected compartment. Regarding the localization of affected organ compartment, presence of liver metastases is linked to shorter survival (22 months) compared to presence of lung metastases (25 months)

Fig. 3

Pretherapeutic [¹⁸F]FDG PET/CT with maximum intensity projections in the middle, transaxial PET/CT and PET, along with immunohistochemistry revealing proliferation index (Ki-67). A 61 year-old male with primary located on the left side, but without metastatic spread. Ki-67 was 10%, i.e. under the median of 24.5%. As such, findings on PET/CT and proliferation index were indicative for prolonged survival. During follow-up, this patient was still alive 53 months after initial diagnosis. B 56 year-old female with primary located on the left side, along with metastases in lung, liver, lymph nodes and bone, i.e. four affected organ compartments derived from PET/CT. Histopathology revealed a Ki-67 of 50%, i.e. above the median of 27.5%. Taken together, immunohistochemistry and findings on pretherapeutic [¹⁸F]FDG PET/CT were indicative for shorter survival and relative to the patient presented in A, this subject succumbed to disease already 18 months after initial diagnosis