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. 2023 Jun 30;14(3):1204-1217.
doi: 10.21037/jgo-22-874. Epub 2023 May 25.

Outcome analysis in patients with metastatic gastroenteropancreatic neuroendocrine tumors receiving peptide receptor radionuclide therapy with Lu-177-DOTATATE

Dominique Prétot  1 , Ivette Engel-Bicik  1 , David Kenkel  1 , Philipp A Kaufmann  1 , Valerie Treyer #  1   2 , Alexander R Siebenhüner #  3   4
Affiliations

Outcome analysis in patients with metastatic gastroenteropancreatic neuroendocrine tumors receiving peptide receptor radionuclide therapy with Lu-177-DOTATATE

Dominique Prétot et al. J Gastrointest Oncol. .

Abstract

Background: Patients with neuroendocrine tumors (NET) of the gastroenteropancreatic tract (GEP-NET) were effectively treated with peptide receptor radionuclide therapy (PRRT) with Lu-177-DOTATATE in the NETTER-1 trial. The aim of this study was to assess the outcome of metastatic GEP-NET patients within a European Neuroendocrine Tumor Society (ENETS) certified center of excellence after this treatment.

Methods: A total of 41 GEP-NET patients who received PRRT with Lu-177-DOTATATE between 2012 and 2017 at a single center were included in this analysis. Data on pre- and post-PRRT treatments [selective internal radiation therapy (SIRT), somatostatin analogue therapy (SSA), blood parameters, patient symptomatic burden and overall survival] was extracted from patient records.

Results: Overall, PRRT was well tolerated and did not increase patient symptomatic burden. Blood parameters were not significantly affected by PRRT (means before and after therapy: hemoglobin: 125.4 vs. 122.3 mg/L, P=0.201; creatinine: 73.8 vs. 77.7 µmol/L, P=0.146), while leukocytes (6.6 vs. 5.6 G/L, P<0.01) and platelets (269.9 vs. 216.7 G/L, P<0.001) were significantly decreased yet without clinical significance in our study. Seven of 9 patients with SIRT treatment prior to PRRT were deceased (mortality odds ratio =4.083). The mortality odds ratio of patients with a pancreatic tumor and SIRT was 1.33 compared to patients with a different tumor origin. 6 of 15 patients (40%) with post-PRRT SSA were deceased (mortality odds ratio =0.429 without SSA after PRRT).

Conclusions: Patients with advanced GEP-NET might benefit from PRRT with Lu-177-DOTATATE as it can provide a valuable treatment modality in advanced disease stages. Safety profiles of PRRT were manageable without increasing the symptomatic burden. SIRT before PRRT or lack of SSA after PRRT seem to impair the response and reduce survival.

Keywords: Lu-177-DOTATATE; Peptide receptor radionuclide therapy (PRRT); health-related quality of life (HRQoL); mortality; neuroendocrine tumors (NET); selective internal radiation therapy (SIRT); somatostatin analogue therapy (SSA).

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-874/coif). ARS has served at advisory boards and received consulting honoraria from AMGEN, AAA, Bayer, BMS, IPSEN, Lilly, Merck, MSD, Pfizer, Roche, Sanofi, and Servier, and has received travel grants from IPSEN and ROCHE, outside the submitted work. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Occurrence of patient symptomatic burden before and 8 weeks after PRRT cycle. 0/0: parameter did not occur before or after PRRT; 0/1: parameter did not occur before PRRT but after PRRT; 1/0: parameter occurred before PRRT but not after PRRT; 1/1: parameter occurred before and after PRRT. PRRT, peptide receptor radionuclide therapy.
Figure 2
Figure 2
Box-plot of blood parameters before (t0) and 8 weeks after (tx) PRRT. (A) Hemoglobin values (y-axis) plotted for each patient (x-axis) before (t0) and 8 weeks after PRRT (tx). (B) Creatinine values (y-axis) plotted for each patient (x-axis) before (t0) and 8 weeks after PRRT (tx). (C) Leukocyte counts (y-axis) plotted for each patient (x-axis) before (t0) and 8 weeks after PRRT (tx). (D) Platelet counts (y-axis) plotted for each patient (x-axis) before (t0) and 8 weeks after PRRT (tx). (E) Glomerular filtration rate levels (y-axis) plotted for each patient (x-axis) before (t0) and 8 weeks after PRRT (tx). (F) Chromogranin A levels (y-axis) plotted for each patient (x-axis) before (t0) and 8 weeks after PRRT (tx). PRRT, peptide receptor radionuclide therapy.
Figure 3
Figure 3
Blood parameters depending on tumor type. Hb, haemoglobin; Lc, leukocytes; Plt, platelets; GFR, glomerular filtration rate; Crea, creatine.
Figure 4
Figure 4
Time point of PRRT in the therapy sequence. Light gray: treatments before PRRT, duration in months [number]; dark gray: treatments after PRRT and duration in months. P-NET, pancreatic neuroendocrine tumors; GE-NET, gastric and enteric NET including large intestine, rectum, paraganglioma; PRRT, peptide receptor radionuclide therapy.
Figure 5
Figure 5
Mortality after SIRT before PRRT (A) and mortality by tumor type (B). SIRT, selective internal radiation therapy; PRRT, peptide receptor radionuclide therapy.
Figure 6
Figure 6
Mortality with or without SSA after PRRT. SSA, somatostatin analogue therapy; PRRT, peptide receptor radionuclide therapy.
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