Inferior outcome of neuroendocrine tumor patients negative on somatostatin receptor imaging

in Endocrine-Related Cancer
Authors:
Julie Refardt ENETS Center of Excellence, Department of Internal Medicine, Section of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands
ENETS Center of Excellence, Department of Endocrinology, University Hospital Basel, Basel, Switzerland
Department of Clinical Research, University of Basel, Basel, Switzerland

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Wouter T Zandee ENETS Center of Excellence, Department of Internal Medicine, Section of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands

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https://orcid.org/0000-0003-1463-5165
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Tessa Brabander ENETS Center of Excellence, Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

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Richard A Feelders ENETS Center of Excellence, Department of Internal Medicine, Section of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands

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Gaston J H Franssen Department of Surgery, Section of Surgical Oncology, Erasmus Medical Center, Rotterdam, The Netherlands

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Leo J Hofland ENETS Center of Excellence, Department of Internal Medicine, Section of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands

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Emanuel Christ ENETS Center of Excellence, Department of Endocrinology, University Hospital Basel, Basel, Switzerland
Department of Clinical Research, University of Basel, Basel, Switzerland

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Wouter W de Herder ENETS Center of Excellence, Department of Internal Medicine, Section of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands

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Johannes Hofland ENETS Center of Excellence, Department of Internal Medicine, Section of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands

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Correspondence should be addressed to J Refardt: julie.refardt@usb.ch
DOI:
https://doi.org/10.1530/ERC-20-0340
Volume/Issue:
Volume 27: Issue 11
Article Type:
Research Article
Page Range:
615–624
Online Publication Date:
Nov 2020
Copyright:
© 2020 Society for Endocrinology 2020
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Sufficient expression of somatostatin receptor (SSTR) in well-differentiated neuroendocrine tumors (NETs) is crucial for treatment with somatostatin analogs (SSAs) and peptide receptor radionuclide therapy (PRRT) using radiolabeled SSAs. Impaired prognosis has been described for SSTR-negative NET patients; however, studies comparing matched SSTR-positive and -negative subjects who have not received PRRT are missing. This retrospective analysis of two prospectively maintained NET databases aimed to compare matched metastatic grade 1 or 2 SSTR-positive and –negative NET patients. SSTR-negativity was defined as having insufficient tumor uptake on diagnostic SSTR imaging. Patients that underwent PRRT were excluded. Seventy-seven SSTR-negative and 248 SSTR-positive grade 1–2 NET patients were included. Median overall survival rates were significantly lower for SSTR-negative compared to SSTR-positive NET patients (53 months vs 131 months; P < 0.001). To adjust for possible confounding by age, gender, grade and site of origin, 69 SSTR-negative NET patients were propensity score matched to 69 SSTR-positive NET patients. Group characteristics were similar, with the exception of SSTR-negative patients receiving more often chemotherapy and targeted treatment. The inferior survival outcome of SSTR-negative compared to SSTR-positive NET patients persisted with a median overall survival of 38 months vs 131 months (P = 0.012). This relationship upheld when correcting for the main influencing factors of having a higher grade tumor or receiving surgery in a multivariate Cox regression analysis. In conclusion, we showed that propensity score-matched SSTR-negative NET patients continue to have a worse prognosis compared to SSTR-positive NET patients despite receiving more aggressive treatment. Differences in tumor biology likely underlie this survival deficit.

Supplementary Materials

    • Table S1 Patient characteristics of PS-matched cohort according to SSTR status. Values are shown as frequencies (%) or median (IQR). p-Value refer to differences between the groups. PS = Propensity score; SSTR = somatostatin receptor; n = number; IQR = interquartile range
    • Table S2: Cox Regression analysis of the propensity score matched cohort. Only variables reaching significance in the univariate analysis were included into the multivariate analysis.
    • Table S3 Patient characteristics of SSA-treated patients according to SSTR status. Values are shown as frequencies (%) or median (IQR). p-Value refers to differences between the groups. SSA = Somatostatin analoga; SSTR = somatostatin receptor; n = number; IQR = interquartile range
    • Table S4 Patient characteristics of PS-matched SSA-treated patients according to SSTR status. Values are shown as frequencies (%) or median (IQR). p-Value refers to differences between the groups. PS = Propensity score; SSA = Somatostatin analoga; SSTR = somatostatin receptor; n = number; IQR = interquartile range
    • Figure S1 Overall Survival Propensity Score-Matched Cohort according to covariates Kaplan Meier analysis showing overall survival of the PS-matched cohort, according to A) SSTR-status and tumour grade 1 (n=60) or 2 (n=78) and B) SSTR-status and having received a surgical intervention (n=82) or not (n=56). p-Value indicates difference in survival between the groups (Log Rank Test). PS = propensity score; SSTR = somatostatin receptor; G1 = grade 1;

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© 2020 Society for Endocrinology 2020
Page(s):
10
Received Date:
17 Aug 2020
Accepted Date:
03 Sep 2020
Print Publication Date:
01 Nov 2020
Online Publication Date:
Nov 2020
Keywords:
somatostatin receptor; neuroendocrine tumor; survival; propensity score

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