Inferior outcome of neuroendocrine tumor patients negative on somatostatin receptor imaging

in Endocrine-Related Cancer
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  • 1 ENETS Center of Excellence, Department of Internal Medicine, Section of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands
  • 2 ENETS Center of Excellence, Department of Endocrinology, University Hospital Basel, Basel, Switzerland
  • 3 Department of Clinical Research, University of Basel, Basel, Switzerland
  • 4 ENETS Center of Excellence, Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
  • 5 Department of Surgery, Section of Surgical Oncology, Erasmus Medical Center, Rotterdam, The Netherlands

Correspondence should be addressed to J Refardt: julie.refardt@usb.ch
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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;

 

      Society for Endocrinology

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