Survival predictors of 177Lu-Dotatate peptide receptor radionuclide therapy (PRRT) in patients with progressive well-differentiated neuroendocrine tumors (NETS)

Abstract

Purpose 177Lu-Dotatate is an emerging treatment modality for patients with unresectable or metastatic well-differentiated NETs. This study examines survival predictors in patients who received 177Lu-Dotatate. Methods A retrospective single-center review was conducted, examining 47 individuals with progressive well-differentiated NETs treated with 177Lu-Dotatate (four induction cycles of 5.5 GBq at 10-week intervals followed by eight maintenance cycles of 3.7 GBq at 6-month intervals). Results Median follow-up was 63.1 months with a median progression-free survival (PFS) of 34.1 months. However, median overall survival (OS) was not reached at the time of analysis. The presence of ≥ 5 bone metastases (hazard ratio HR 4.33; p = 0.015), non-gastroenteropancreatic (non-GEP) NETs (HR 3.22; p = 0.025) and development of interim ascites (HR 3.15; p = 0.047) independently predicted a worse OS. Patients with chromogranin A of ≥ 4 × upper limit of normal (ULN) had shorter OS (p < 0.001) and PFS (p = 0.004). Similarly, those with pre-existing ascites demonstrated a worse OS (p = 0.009) and PFS (p = 0.026). Liver metastases involving greater than 50% liver volume and the existence of unusual metastatic locations had a negative impact on OS (p = 0.033) and PFS (p = 0.026), respectively. Conclusion High burden of skeletal and hepatic metastases, non-GEP-NETs, chromogranin A of ≥ 4 × ULN, unusual metastatic sites, pre-existing and interim ascites are predictors of poor outcomes in patients treated with 177Lu-Dotatate. These common indicators can be used for the risk stratification and identification of patients most likely to benefit from PRRT. Trial registration ClinicalTrials.gov identifier: NCT02236910, Retrospectively registered on September, 2014.

New Insights in PRRT: Lessons From 2021

“…A study by Papantoniou et al. ( 34 ) demonstrated that changes in chromogranin A and 5-hydroxyindoleacetic acid during treatment were not predictors of PRRT response ( 34 ), although baseline values correlated to PFS ( 34 , 35 ).…”

“…Many clinical parameters have been proposed as prognostic markers. Factors associated with a reduction in PFS and OS in PRRT-treated patients were ascites ( 35 ), marked liver metastasis burden ( 18 , 25 , 35 ), unusual metastatic sites ( 35 ), and age >65 years at the time of PRRT ( 18 ). Other factors such as interim ascites, the presence of ≥5 bone metastases, and NETs other than GEP were predictors of worse OS ( 35 ).…”

“…Factors associated with a reduction in PFS and OS in PRRT-treated patients were ascites ( 35 ), marked liver metastasis burden ( 18 , 25 , 35 ), unusual metastatic sites ( 35 ), and age >65 years at the time of PRRT ( 18 ). Other factors such as interim ascites, the presence of ≥5 bone metastases, and NETs other than GEP were predictors of worse OS ( 35 ). The importance of bone metastasis is also confirmed by the evidence that an increase in baseline alkaline phosphatase is associated with poorer PFS and OS ( 25 , 26 ).…”

Predictive Factors for Resistant Disease with Medical/Radiologic/Liver-Directed Anti-Tumor Treatments in Patients with Advanced Pancreatic Neuroendocrine Neoplasms: Recent Advances and Controversies

“…Various biological markers predictive for outcomes of PRRT have been studied. An elevated baseline level of CgA is associated with both decreased post-PRRT PFS [ 114 , 184 , 189 , 190 ] and OS [ 114 , 184 , 190 , 191 , 192 ]. A biochemical response in CgA levels is significantly associated with longer post-PRRT survival [ 184 , 193 ], while increases in CgA levels after PRRT correlates with worse OS [ 191 ].…”

“…Patients with bone metastases [ 59 , 183 , 184 , 187 , 188 , 190 , 198 , 214 ] as well as with higher hepatic tumor load [ 59 , 62 , 183 , 184 , 186 , 190 , 213 ] are reported to have a worse clinical outcome of PRRT. In addition to the findings that poor performance status, as well as previous treatment correlate with worse outcomes, as mentioned above, early initiation of PRRT can maximize its anti-tumor activity [ 282 ], which needs to be validated by prospective, randomized studies with other therapeutic agents.…”