Volumetric and texture analysis of pretherapeutic 18F-FDG PET can predict overall survival in medullary thyroid cancer patients treated with Vandetanib

Rudolf A Werner,Michael C Kreissl,Norbert Zsótér,Takahiro Higuchi,Constantin Lapa,Matthias Kroiss,Ralph A Bundschuh,Andreas K Buck,Mehrbod S Javadi,Martin Fassnacht,Steven P Rowe

doi:10.1007/s12020-018-1749-3

Abstract

PurposeThe metabolically most active lesion in 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) PET/CT can predict progression-free survival (PFS) in patients with medullary thyroid carcinoma (MTC) starting treatment with the tyrosine kinase inhibitor (TKI) vandetanib. However, this metric failed in overall survival (OS) prediction. In the present proof of concept study, we aimed to explore the prognostic value of intratumoral textural features (TF) as well as volumetric parameters (total lesion glycolysis, TLG) derived by pre-therapeutic 18F-FDG PET.MethodsEighteen patients with progressive MTC underwent baseline 18F-FDG PET/CT prior to and 3 months after vandetanib initiation. By manual segmentation of the tumor burden at baseline and follow-up PET, intratumoral TF and TLG were computed. The ability of TLG, imaging-based TF, and clinical parameters (including age, tumor marker doubling times, prior therapies and RET (rearranged during transfection) mutational status) for prediction of both PFS and OS were evaluated.ResultsThe TF Complexity and the volumetric parameter TLG obtained at baseline prior to TKI initiation successfully differentiated between low- and high-risk patients. Complexity allocated 10/18 patients to the high-risk group with an OS of 3.3 y (vs. low-risk group, OS = 5.3 y, 8/18, AUC = 0.78, P = 0.03). Baseline TLG designated 11/18 patients to the high-risk group (OS = 3.5 y vs. low-risk group, OS = 5 y, 7/18, AUC = 0.83, P = 0.005). The Hazard Ratio for cancer-related death was 6.1 for Complexity (TLG, 9.5). Among investigated clinical parameters, the age at initiation of TKI treatment reached significance for PFS prediction (P = 0.02, OS, n.s.).ConclusionsThe TF Complexity and the volumetric parameter TLG are both independent parameters for OS prediction.

Highlights

The tyrosine kinase inhibitor (TKI) vandetanib, a selective inhibitor of wild-type rearranged during transfection (RET) kinase as well as of vascular endothelial growth factor receptor (VEGFR) signaling [1,2,3], has demonstrated a favorable disease control in patients suffering from advanced medullary thyroid carcinoma (MTC) [4, 5]
In the present proof of concept study, we aimed to explore, if intratumoral heterogeneity textural features (TF) as well as volumetric parameters derived from 18FFDG positron emission tomography (PET) prior to and 3 months after vandetanib initiation succeeded in prognostication in patients with advanced MTC
In the non-hereditary cases with available somatic RET mutational status, a somatic RET mutation was found in 3/8 cases (37.5%). 18FFDG PET was positive in the entire cohort, with 17/18 (94.4%) patients presenting with lymph node involvement and 10/18 (55.6%) with lung metastases. 9/18 (50.0%) patients had liver lesions, 9/18 (50.0%) had bone lesions, 2/18 (11.1%) had soft tissue metastases, and a single subject (1/18, 5.6%) suffered from infiltration of the pancreas (Supplementary Table 1)

Summary

Introduction

The tyrosine kinase inhibitor (TKI) vandetanib, a selective inhibitor of wild-type rearranged during transfection (RET) kinase as well as of vascular endothelial growth factor receptor (VEGFR) signaling [1,2,3], has demonstrated a favorable disease control in patients suffering from advanced medullary thyroid carcinoma (MTC) [4, 5]. Volumetric assessment of tumor burden (i.e., metabolic tumor volume (MTV) or Total lesion glycolysis (TLG)) on 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography (PET) has been demonstrated as a useful tool for outcome prediction in various tumor entities, including salivary gland carcinoma, pancreatic cancer, and colorectal cancer [9,10,11]. Intratumoral heterogeneity (tumor texture) analysis is currently gaining ground to serve as a potential risk stratification tool in a variety of different cancer entities [14,15,16,17,18,19]. Not surprisingly, combined 18F-FDG PET-based approaches (i.e., volumetric plus tumor texture assessment) for outcome prediction have been investigated, e.g. in esophageal cancer [20]

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