title: Assessment of tumor heterogeneity in treatment-naïve adrenocortical cancer patients using (18)F-FDG positron emission tomography.
abstract: As an orphan malignancy, only limited treatment options are available in adrenocortical carcinoma (ACC). Non-invasive risk assessment has not been described but may be of value to stratify patients for treatment. We aimed to evaluate the potential value of intra-individual tumor heterogeneity as assessed by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) for outcome prediction in treatment-naïve ACC patients. Ten patients with primary diagnosis of ACC were included in this study. Prior to any treatment initiation, baseline (18)F-FDG PET scans were performed. Tumor staging was performed using the European Network for the Study of Adrenal Tumors (ENS@T). Intratumoral heterogeneity of the primary tumor was assessed by manual segmentation using conventional PET parameters (standardized uptake values and tumor-to-liver ratios) and textural features. The impact of tumoral heterogeneity based on pre-therapeutic (18)F-FDG PET to predict progression-free (PFS) and overall survival (OS) was evaluated by receiver operating characteristic analysis. On average, tumor recurrence or progression was detected after median of 561 days (range 71-1434 days) after the pre-therapeutic baseline PET scan. 50 % of the patients died of ACC within the follow-up period (mean 983 ± 404 days). Pre-therapeutic tumor volume was associated with PFS (r = -0.67, p = 0.05) and Ki67 index with OS (r = -0.66, p = 0.04). ENS@T tumor stage was the only parameter to correlate with both PFS and OS (r = -0.82, p = 0.001, and r = -0.72, p = 0.01, respectively). In the subgroup of patients without distant metastases (ENS@T stages II and III), age and pre-therapeutic tumor volume correlated significantly with PFS (r = 0.96, p = 0.01 and r = -0.93, p = 0.02, respectively) and OS (r = 0.95, p = 0.02 and r = -0.90, p = 0.04, respectively). None of the investigated classic or textural PET parameters predicted PFS or OS. In this pilot study in treatment-naïve ACC patients, conventional (18)F-FDG PET-derived parameters and textural tumor heterogeneity features were not suitable to identify high-risk patients.
authors.affiliation: Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.|Comprehensive Heart Failure Center, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: Werner
authors.affiliation: Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital Würzburg, Würzburg, Germany.|Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kroiss
authors.affiliation: Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.|Comprehensive Heart Failure Center, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Masatoyo
authors.initials: M
authors.lastname: Nakajo
authors.affiliation: University of Applied Science, Hamburg, Germany.
authors.forename: Dirk O
authors.initials: DO
authors.lastname: Mügge
authors.affiliation: Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hahner
authors.affiliation: Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital Würzburg, Würzburg, Germany.|Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Fassnacht
authors.affiliation: Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schirbel
authors.affiliation: Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Bluemel
authors.affiliation: Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.|Comprehensive Heart Failure Center, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Higuchi
authors.affiliation: Mediso Medical Imaging Systems Ltd., Budapest, Hungary.
authors.forename: Laszló
authors.initials: L
authors.lastname: Papp
authors.affiliation: Mediso Medical Imaging Systems Ltd., Budapest, Hungary.
authors.forename: Norbert
authors.initials: N
authors.lastname: Zsótér
authors.affiliation: Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.|Comprehensive Heart Failure Center, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Andreas K
authors.initials: AK
authors.lastname: Buck
authors.affiliation: Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany. ralph.bundschuh@ukb.uni-bonn.de.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Bundschuh
authors.affiliation: Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Constantin
authors.initials: C
authors.lastname: Lapa
mesh_terms: D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D018268:Adrenocortical Carcinoma / Q000000981:diagnostic imaging* / Q000473:pathology; D000328:Adult; D000368:Aged; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D011379:Prognosis; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: ACC; FDG PET; Textural features; Tumor heterogeneity