The Prognostic Value of the De Ritis Ratio for Progression-Free Survival in Patients with NET Undergoing [(177)Lu]Lu-DOTATOC-PRRT: A Retrospective Analysis

SIMPLE SUMMARY: Peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NET) has shown variable response rates between 9% and 39%. Therefore, better criteria are needed that help doctors to identify patients who will show a favorable outcome to PRRT, and which patients may not. The so-called De Ritis ratio, which is calculated using two basic laboratory parameters of liver function, has shown that it can help to predict the patient outcome in various tumor types. This retrospective study included 125 patients with NET who were treated with PRRT. We demonstrated that a high De Ritis ratio and high levels of the tumor marker Chromogranin A (CgA) each improved the prediction of the progression-free survival after treatment. A consequence for clinical care might be that patients with both high De Ritis ratio and high CgA levels may benefit from intensified follow-up imaging after PRRT because they have a higher risk of early progression. ABSTRACT: Background: The De Ritis ratio (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]) has demonstrated prognostic value in various cancer entities. We evaluated the prognostic capability of the De Ritis ratio in patients with metastatic neuroendocrine tumors (NET) undergoing peptide receptor radionuclide therapy (PRRT). Methods: Unicentric, retrospective analysis of 125 patients with NET undergoing PRRT with [(177)Lu]Lu-DOTATOC (female: 37%; median age: 66 years; G1+G2 NET: 95%). The prognostic value regarding progression-free survival (PFS) was analyzed with univariable and multivariable Cox regression. Prognostic accuracy was determined with Harrell’s C index and a likelihood ratio test. Results: Progression, relapse, or death after PRRT was observed in 102/125 patients. Median progression-free survival (PFS) was 15.8 months. Pancreatic or pulmonary origin, high De Ritis ratio, and high Chromogranin A (CgA) significantly predicted shorter PFS in univariable Cox. In multivariable Cox regression, only high De Ritis ratio >0.927 (HR: 1.7; p = 0.047) and high CgA >twice the upper normal limit (HR: 2.1; p = 0.005) remained independent predictors of shorter PFS. Adding the De Ritis ratio to the multivariable Cox model (age, Eastern Cooperative Oncology Group (ECOG) performance status, primary origin, CgA) significantly improved prognostic accuracy (p < 0.001). Conclusions: The De Ritis ratio is simple to obtain in clinical routine and can provide independent prognostic value for PFS in patients with NET undergoing PRRT.