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Am J Nucl Med Mol Imaging 2013;3(5):437-445
Original Article
Bone metastases in GEP-NET: response and long-term outcome after PRRT from a
follow-up analysis
Amir Sabet, Feras Khalaf, Torjan Haslerud, Abdullah Al-Zreiqat, Amin Sabet, Birgit Simon, Thorsten D Pöppel, Hans-Jürgen Biersack,
Samer Ezziddin
Department of Nuclear Medicine, University Hospital, Bonn, Germany; Department of Radiology, University Hospital, Bonn, Germany;
Department of Nuclear Medicine, University Hospital, Esssen, Germany
Received July 24, 2013; Accepted August 18, 2013; Epub September 19, 2013; Published September 30, 2013
Abstract: Bone metastases of gastroenteropancreatic neuroendocrine tumors (GEP NET) can be associated with pain and a poor
prognosis. Peptide receptor radionuclide therapy (PRRT) has been shown to be effective against this tumor manifestation. This
study represents an update of the therapeutic assessment of PRRT with 177Lu-octreotate in GEP NET patients with bone
metastases focusing on potential predictors for impaired outcome and overall survival. We retrospectively analyzed a consecutive
subgroup of n=68 patients with bone metastases (BM) of GEP NET treated with 177Lu-octreotate (4 intended cycles at 3 monthly
intervals; mean activity per cycle, 8.1 GBq). Baseline characteristics, including age, performance status, tumor origin, tumor load,
plasma chromogranin A (CgA), and neuron-specific enolase (NSE) were analyzed regarding the impact on tumor regression
(modified M.D. Anderson criteria) and survival of the patients. Survival analyses were performed using Kaplan–Meier curves, log-rank
test at a significance level of p <0.05, and Cox proportional hazards model for uni- and multivariate analyses. Median follow-up was
48 months. The observed response of BMs consisted of complete remission in 2 (2.9%), partial remission in 23 (33.8%), minor
response in 8 (11.8%), stable disease in 26 (38.2%), and progressive disease in 8 (13.2%) patients. Median time-to-progression
(TTP) of BMs and overall survival (OS) were 35 mo (95% CI: 25-45) and 51 mo (95% CI: 38-64), respectively. Patients with
responding BMs survived significantly longer than other patients (median 56 mo vs. 39 mo, p=0.034). NSE >15 ng/ml (p=0.002) and
Ki67 index >10% (p=0.008) were associated with shorter overall survival. BM of GEP NET are effectively controlled by PRRT with a
long median progression-free survival of approx. 3 years. Non-regression of BM, high proliferation rate and increased plasma NSE at
baseline are predictive of shorter survival. However, this study confirms that poor patient condition (Karnofsky-Index ≤70%) and
multifocality of BM (>10 lesions) do not affect outcome efficacy, further encouraging the use of PRRT in advanced bone metastatic
disease. (ajnmmi1307004).
Keywords: Bone metastases, gastroenteropancreatic neuroendocrine tumors (GEP NET), peptide receptor radionuclide therapy
(PRRT)
Address correspondence to: Dr. Samer Ezziddin, Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str.
25, D-53105 Bonn, Germany. Tel: +49 228 287–19174; Fax: +49 228 287–9019174; E-mail: samer.ezziddin@ukb.uni-bonn.de
Original Article
Bone metastases in GEP-NET: response and long-term outcome after PRRT from a
follow-up analysis
Amir Sabet, Feras Khalaf, Torjan Haslerud, Abdullah Al-Zreiqat, Amin Sabet, Birgit Simon, Thorsten D Pöppel, Hans-Jürgen Biersack,
Samer Ezziddin
Department of Nuclear Medicine, University Hospital, Bonn, Germany; Department of Radiology, University Hospital, Bonn, Germany;
Department of Nuclear Medicine, University Hospital, Esssen, Germany
Received July 24, 2013; Accepted August 18, 2013; Epub September 19, 2013; Published September 30, 2013
Abstract: Bone metastases of gastroenteropancreatic neuroendocrine tumors (GEP NET) can be associated with pain and a poor
prognosis. Peptide receptor radionuclide therapy (PRRT) has been shown to be effective against this tumor manifestation. This
study represents an update of the therapeutic assessment of PRRT with 177Lu-octreotate in GEP NET patients with bone
metastases focusing on potential predictors for impaired outcome and overall survival. We retrospectively analyzed a consecutive
subgroup of n=68 patients with bone metastases (BM) of GEP NET treated with 177Lu-octreotate (4 intended cycles at 3 monthly
intervals; mean activity per cycle, 8.1 GBq). Baseline characteristics, including age, performance status, tumor origin, tumor load,
plasma chromogranin A (CgA), and neuron-specific enolase (NSE) were analyzed regarding the impact on tumor regression
(modified M.D. Anderson criteria) and survival of the patients. Survival analyses were performed using Kaplan–Meier curves, log-rank
test at a significance level of p <0.05, and Cox proportional hazards model for uni- and multivariate analyses. Median follow-up was
48 months. The observed response of BMs consisted of complete remission in 2 (2.9%), partial remission in 23 (33.8%), minor
response in 8 (11.8%), stable disease in 26 (38.2%), and progressive disease in 8 (13.2%) patients. Median time-to-progression
(TTP) of BMs and overall survival (OS) were 35 mo (95% CI: 25-45) and 51 mo (95% CI: 38-64), respectively. Patients with
responding BMs survived significantly longer than other patients (median 56 mo vs. 39 mo, p=0.034). NSE >15 ng/ml (p=0.002) and
Ki67 index >10% (p=0.008) were associated with shorter overall survival. BM of GEP NET are effectively controlled by PRRT with a
long median progression-free survival of approx. 3 years. Non-regression of BM, high proliferation rate and increased plasma NSE at
baseline are predictive of shorter survival. However, this study confirms that poor patient condition (Karnofsky-Index ≤70%) and
multifocality of BM (>10 lesions) do not affect outcome efficacy, further encouraging the use of PRRT in advanced bone metastatic
disease. (ajnmmi1307004).
Keywords: Bone metastases, gastroenteropancreatic neuroendocrine tumors (GEP NET), peptide receptor radionuclide therapy
(PRRT)
Address correspondence to: Dr. Samer Ezziddin, Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str.
25, D-53105 Bonn, Germany. Tel: +49 228 287–19174; Fax: +49 228 287–9019174; E-mail: samer.ezziddin@ukb.uni-bonn.de
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