AUTHOR=Trautwein Nils Florian , Schwenck Johannes , Jacoby Johann , Reischl Gerald , Fiz Francesco , Zender Lars , Dittmann Helmut , Hinterleitner Martina , la Fougère Christian 

TITLE=Long-term prognostic factors for PRRT in neuroendocrine tumors

JOURNAL=Frontiers in Medicine

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1169970

DOI=10.3389/fmed.2023.1169970

ISSN=2296-858X

ABSTRACT=Aim/Introduction: Peptide receptor radionuclide therapy (PRRT) is an effective and well-tolerated treatment option for patients with neuroendocrine tumors (NETs) that prolongs progression-free survival (PFS). However, the limited overall survival (OS) rates in the prospective phase III study (NETTER1) highlighted the need to identify patient-specific long-term prognostic markers. Therefore, we retrospectively analyzed prognostic risk factors in NET patients treated with PRRT.
Methods: 62 NET patients (G1: 33.9%, G2 62.9%, G3 3.2%) with at least 2 cycles of PRRT with [177Lu]Lu-HA-DOTATATE (mean 4 cycles) were analyzed. 53 patients had primary tumors in the gastroenteropancreatic (GEP) system, six had bronchopulmonary NET and three had NET of unknown origin. [68Ga]Ga-HA-DOTATATE PET/CT scans were performed before PRRT start and after the second treatment cycle. Different clinical laboratory parameters, as well as PET parameters such as SUVmean, SUVmax, PET-based molecular tumor volume (MTV) were collected and their impact on the OS were investigated. Patient data with a mean follow-up of 62 months (range 20 – 105) were analyzed.
Results: According to interim PET/CT, 16 patients (25.8%) presented with partial response (PR), 38 (61.2%) with stable disease (SD) and 7 (11.3%) with progressive disease (PD). The 5-year OS was 61.8% for all patients, while bronchopulmonary NETs showed a poorer OS than GEP-NETs. Multivariable Cox-Regression analysis showed that chromogranin A level and MTV together were highly significant predictors of therapeutic outcome (HR 2.67; 95% CI 1.41-4.91; p = 0.002). Treatment response was also influenced by the LDH level (HR 0.98; 95% CI 0.98-1.0; p = 0.007) and patient age (HR 1.15; 95% CI 1.08-1.23; p < 0.001). ROC-analysis revealed baseline MTV >112.5 ml (Sens. 91%; Spec. 50%; AUC 0.67 (95% CI 0.51-0.84, p=0.043)) and chromogranin A >1250.75 µg/l (Sens. 87%; Spec. 56%; AUC 0.73 (95% CI 0.57-0.88, p=0.009) as the best cut off value for identifying patients with a worse five-year survival.
Conclusion: Our retrospective analysis defined MTV and chromogranin A in combination as significant prognostic factors for long-term OS. Furthermore, an interim PET/CT after two cycles has the potential to identify non-responders who may benefit from a change in therapy at an early stage.