Plasma Markers for Therapy Response Monitoring in Patients with Neuroendocrine Tumors Undergoing Peptide Receptor Radionuclide Therapy.

Simple Summary: Peptide receptor radionuclide therapy is a well-established therapy for the treatment of neuroendocrine tumors. Therapy typically consists of four cycles administered in 8–10 week intervals, resulting in an average treatment length of 8–10 months. Given the extensive treatment length, early identification of patients with disease progression could help to optimize disease management. Blood-based biomarkers such as chromogranin A, alkaline phosphatase (ALP), or the De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) are continually assessed during treatment and represent a noninvasive and easily accessible source for the intratherapeutic monitoring of patients. Our exploratory analysis indicates that a considerable intratherapeutic increase in ALP may serve as a tool to identify patients who are at a higher risk of early disease progression after PRRT. If our results can be confirmed by other studies, these patients might benefit from intensified follow-up. Background: Pretherapeutic chromogranin A, alkaline phosphatase (ALP), or De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) are prognostic factors in patients with metastatic neuroendocrine tumors (NET) undergoing peptide receptor radionuclide therapy (PRRT). However, their value for intratherapeutic monitoring remains unclear. We evaluated if changes in plasma markers during PRRT can help identify patients with unfavorable outcomes. Methods: A monocentric retrospective analysis of 141 patients with NET undergoing PRRT with [¹⁷⁷Lu]Lu-DOTATOC was conducted. Changes in laboratory parameters were calculated by dividing the values determined immediately before each cycle of PRRT by the pretherapeutic value. Patients with low vs. high PFS were compared with the Wilcoxon rank-sum test. Results: Progression, relapse, or death after PRRT was observed in 103/141 patients. Patients with low PFS showed a significant relative ALP increase before the third (p = 0.014) and fourth (p = 0.039) cycles of PRRT. Kaplan–Meier analysis revealed a median PFS of 24.3 months (95% CI, 20.7–27.8 months) in patients with decreasing ALP values (Δ > 10%) during treatment, 12.5 months (95% CI, 9.2–15.8 months) in patients with increasing ALP values (Δ > 10%), and 17.7 months (95% CI, 13.6–21.8 months) with stable ALP values (Δ ± 10%). Conclusions: Based on these exploratory data, a rise in plasma ALP might indicate disease progression and should be interpreted cautiously during therapy. [ABSTRACT FROM AUTHOR]