Long-term results and tolerability of tandem peptide receptor radionuclide therapy with90Y/177Lu-DOTATATE in neuroendocrine tumors with respect to the primary location: a 10-year study.
BACKGROUND
The peptide receptor radionuclide therapy (PRRT) with90Y and177Lu is a form of molecular targeted therapy for inoperable or disseminated neuroendocrine tumors (NET).


OBJECTIVE
The aim of the study was to evaluate clinical results and long-term side effects of tandem90Y /177Lu-DOTATATE therapy in patients with NET. Additionally, we evaluated clinical results with reference to the primary site.


METHODS
59 patients with disseminated NET were included in the study prospectively. 3-5 cycles of combined 1:190Y/177Lu-DOTATATE (total injected activity 11.1-16.65 GBq) with mixed amino acids for kidney protection were performed.


RESULTS
During a median follow-up of 75.8 months, the PFS was 32.2 months, and the OS was 82 months; 25 patients died. Depending on primary tumor's site, the PFS and the OS for pancreatic NET vs. small bowel, NET vs. large bowel, NET were 30.4 vs. 29.5 vs. 40.3 and 78.9 vs. 58.1 vs. 82.5, respectively. The observed 5-year overall survival was 63%, and a 2-year risk of progression was 39.4%. The following imaging response was observed: CR in 2%, PR in 22%, SD in 65%, and PD in 6% patients. The disease control rate was 89%. The objective response rate was 24%. The PRRT was well tolerated by all patients. One patient (2%) revealed MDS, and one patient (2%) grade 3 nephrotoxicity. No other grade 3 and 4 hematological or renal toxicity was observed.


CONCLUSIONS
These results indicated the tandem90Y/177Lu-DOTATATE therapy for patients with disseminated/inoperable NET as highly effective and safe, considering long-term side effects. In the majority of patients, clinical improvement was observed.
Nuclear Medicine Department, Medical University of Warsaw, ul. Banacha 1 a, 02-097, Warsaw, Poland. jolanta.kunikowska@wum.edu.pl.
Jolanta
J
Kunikowska
Radioisotope Centre POLATOM, National Centre for Nuclear Research, ul. Andrzeja Sołtana 7, 05-400, Otwock-Świerk, Poland.
Dariusz
D
Pawlak
Department of Internal Medicine and Diabetology, Medical University of Warsaw, ul. Banacha 1 a, 02-097, Warsaw, Poland.
Marianna I
MI
Bąk
Division of Endocrinology, Department of Pathophysiology and Endocrinology, Medical University of Silesia, ul. Ceglana 35, 40-514, Katowice, Poland.
Beata
B
Kos-Kudła
Radioisotope Centre POLATOM, National Centre for Nuclear Research, ul. Andrzeja Sołtana 7, 05-400, Otwock-Świerk, Poland.
Renata
R
Mikołajczak
Nuclear Medicine Department, Medical University of Warsaw, ul. Banacha 1 a, 02-097, Warsaw, Poland.
Leszek
L
Królicki
D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000009:adverse effects* / Q000627:therapeutic use*; D000072078:Positron Emission Tomography Computed Tomography; D018000:Receptors, Peptide / Q000378:metabolism*; D012449:Safety; D013997:Time Factors; D016896:Treatment Outcome
C539274:90Y-octreotate, DOTA(0)-Tyr(3)-Thr(8)-; D009942:Organometallic Compounds; D018000:Receptors, Peptide; C447941:lutetium Lu 177 dotatate; D015282:Octreotide
90Y/177Lu-DOTATATE; Neuroendocrine tumors.; PRRT; Somatostatin receptor; Tandem therapy