Abstract
Simple SummaryPeptide 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.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 [177Lu]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.
Highlights
Neuroendocrine tumors (NET) of the bronchopulmonary or gastroenteropancreatic system (GEP-neuroendocrine tumors (NET)) represent a rare and heterogeneous class of tumors [1]
The primary aim of this study was to evaluate the prognostic value of the pretherapeutic De Ritis ratio on the progression-free survival (PFS) in patients with NET undergoing peptide receptor radionuclide therapy (PRRT)
In 64/125 patients (51%), the primary tumor was located in the gastrointestinal tract, 30/125 patients (24%) showed a pancreatic primary, 11/125 patients (9%) had a pulmonary primary, and 20/125 patients (16%) suffered from cancer of unknown primary (CUP)
Summary
Neuroendocrine tumors (NET) of the bronchopulmonary (lung-) or gastroenteropancreatic system (GEP-NET) represent a rare and heterogeneous class of tumors [1]. The NETTER-1 study, the first randomized controlled trial in patients with metastasized GEP-NET and treatment with. PRRT, showed an average therapy response rate of 18% in these patients [4]. Many retrospective studies found response rates between 9 and 39% [5,6]. A recent meta-analysis including 11 studies and 1268 patients reported an average response rate of 29.1% [7]. Better stratification criteria are highly desirable to identify patients who will show a favorable response and longer progression-free survival (PFS) after PRRT. We evaluated the prognostic capability of the De Ritis ratio in patients with metastatic neuroendocrine tumors (NET). 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).
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