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. 2014 Dec 15;5(1):46-55.
eCollection 2015.

Survival after somatostatin based radiopeptide therapy with (90)Y-DOTATOC vs. (90)Y-DOTATOC plus (177)Lu-DOTATOC in metastasized gastrinoma

Rebecca A Dumont  1 , Daniela Seiler  2 , Nicolas Marincek  3 , Philippe Brunner  2 , Piotr Radojewski  4 , Christoph Rochlitz  5 , Jan Müller-Brand  2 , Helmut R Maecke  6 , Matthias Briel  7 , Martin A Walter  3
Affiliations

Survival after somatostatin based radiopeptide therapy with (90)Y-DOTATOC vs. (90)Y-DOTATOC plus (177)Lu-DOTATOC in metastasized gastrinoma

Rebecca A Dumont et al. Am J Nucl Med Mol Imaging. .

Abstract

We aimed to explore the effects of (90)Y-DOTATOC and (90)Y-DOTATOC plus (177)Lu-DOTATOC on survival of patients with metastasized gastrinoma. Patients with progressive metastasized gastrinoma were treated with repeated cycles of (90)Y-DOTATOC or with cycles alternating between (90)Y-DOTATOC and (177)Lu-DOTATOC until tumor progression or permanent toxicity. Multivariable Cox regression analyses were used to study predictors of survival. A total of 36 patients were enrolled; 30 patients received (90)Y-DOTATOC (median activity per patient 11.8GBq; range: 6.1-62.2GBq) and 6 patients received (90)Y-DOTATOC plus (177)Lu-DOTATOC (median activity per patient: 14.8GBq; range: 7.4-14.8GBq). Response was found in 26 patients (72.2%), including morphological (n=12, 33.3%), biochemical (n=14, 38.9%) and/or clinical response (n=6, 16.2%). A total of 21 patients (58.3%) experienced hematotoxicity grade 1/2, while 1 patient (2.8%) experienced hematotoxicity grade 3; no grade 4 hematotoxicity occurred. Furthermore, 2 patients (5.6%) developed grade 4 renal toxicity; no grade 5 renal toxicity occurred. Responders had a significantly longer median survival from time of enrollment than non-responders (45.1 months, range: 37.1-53.1 months vs. 12.6 months, range: 11.0-14.2, hazard ratio: 0.12 (0.027-0.52), p=0.005). Additionally, there was a trend towards longer median survival with (90)Y-DOTATOC plus (177)Lu-DOTATOC as compared to (90)Y-DOTATOC alone (60.2 months, range: 19.8-100.6 months vs. 27.0 months, range: 4.0-50.0, hazard ratio: 0.21 (0.01-3.98), p=0.16). Response to (90)Y-DOTATOC and (90)Y-DOTATOC plus (177)Lu-DOTATOC therapy is associated with a longer survival in patients with metastasized gastrinoma. Both treatment regimens are promising tools for management of progressive gastrinoma.

Keywords: Yttrium; gastrinoma; lutetium; somatostatin; survival.

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Figures

Figure 1
Figure 1
Patient Flow.
Figure 2
Figure 2
Example of a 51-year old man with metastasized gastrinoma. The intratherapeutic 111In-DOTATOC-scan displays focal grade 4 tracer uptake in the liver, right lung, left scapula, spine, ribs, pelvis and left humerus (A). Co-registered SPECT-CT confirms specific uptake in liver metastases (B). The thoracic lesion is confirmed as a sternal metastasis via SPECT-CT (arrow, C). High uptake in viable tumor and absent uptake in necrotic parts of metastases is demonstrated (arrow, D). The serum gastrin did not drop after the first four treatment cycles; however, at later cycles a significant drop in serum gastrin levels occurred.
Figure 3
Figure 3
Pre- and post-therapeutic serum gastrin levels in all patients (A), biochemical responders (B) and biochemical non-responders (C).
Figure 4
Figure 4
Survival of responders vs. non-responders in the uni-variable (A) and multivariable analysis (B). Survival of patients treated with 90Y-DOTATOC vs. patients treated with 90Y-DOTATOC plus 177Lu-DOTATOC in the uni-variable (C) and multivariable analysis (D).
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