Abstract
The NETTER-1 trial demonstrated significantly improved progression-free survival (PFS) for peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors (NET) emphasizing the high demand for response prediction in appropriate candidates. In this multicenter study, we aimed to elucidate the prognostic value of tumor heterogeneity as assessed by somatostatin receptor (SSTR)-PET/CT. 141 patients with SSTR-expressing tumors were analyzed obtaining SSTR-PET/CT before PRRT (1-6 cycles, 177Lu somatostatin analog). Using the Interview Fusion Workstation (Mediso), a total of 872 metastases were manually segmented. Conventional PET parameters as well as textural features representing intratumoral heterogeneity were computed. The prognostic ability for PFS and overall survival (OS) were examined. After performing Cox regression, independent parameters were determined by ROC analysis to obtain cut-off values to be used for Kaplan-Meier analysis. Within follow-up (median, 43.1 months), 75 patients showed disease progression (median, 22.2 m) and 54 patients died (median, 27.6 m). Cox analysis identified 8 statistically independent heterogeneity parameters for time-to-progression and time-to-death. Among them, the textural feature Entropy predicted both PFS and OS. Conventional PET parameters failed in response prediction. Imaging-based heterogeneity assessment provides prognostic information in PRRT candidates and outperformed conventional PET parameters. Its implementation in clinical practice can pave the way for individualized patient management.
Highlights
Over the past decades, a rising incidence of neuroendocrine tumors (NET) has been reported [1]
Baseline positron emission tomography (PET) was positive in all patients as a prerequisite for treatment initiation. 120/141 (85.1%) subjects suffered from liver metastases, more than half of the cohort demonstrated lymph node metastases (78/141, 55.3%), one third suffered from bone lesions (53/141, 37.6%) and 16/141 (11.3%) demonstrated pulmonary metastases (Table 1)
We investigated the prognostic value of PET-assessed tumor heterogeneity in patients scheduled for peptide receptor radionuclide therapy (PRRT)
Summary
A rising incidence of neuroendocrine tumors (NET) has been reported [1]. Non-invasive, whole-body assessment of tumor heterogeneity www.impactjournals.com/oncotarget. * = median and range is given, # = including meningeoma, hemangioendothelioma, pheochromocytoma, medullary thyroid carcinoma and pituitary tumor. GBq = Gigabecquerel, GEP-NET = gastroenteropancreatic neuroendocrine tumors, MBq = Megabecquerel, PRRT = Peptide Receptor Radionuclide Therapy, SSTR-PET/CT = somatostatin receptor positron emission tomography/computed tomography. Due to its ability to visualize functional alterations on a molecular level instead of pure morphological characteristics, positron emission tomography (PET) has proven its prognostic value in risk stratification for several types of cancer [4,5,6]
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