Can SSTR2 expression in previously resected SI-NETs predict overall survival after PRRT treatment of remaining lesions?

Purpose Small intestinal neuroendocrine tumours (SI-NET) often present with distant metastases at diagnosis. Peptide receptor radiotherapy (PRRT) with radiolabelled somatostatin analogues is a systemic treatment that increases overall survival (OS) in patients with SI-NET. However, PRRT treatment response is variable and predictive factors have not been established. PRRT predominantly targets somatostatin receptor 2 (SSTR2). This study evaluates if SSTR2 expression in SI-NET tumours predicts OS after PRRT treatment.Methods Using a previously constructed Tissue Micro Array (TMA) consisting of 412 SI-NET patients we identified a subgroup consisting of 44 patients (95 tissue samples) that had received PRRT treatment during 2006-2016 at Sahlgrenska University hospital. IHC expression of SSTR2, Ki-67 and neuroendocrine markers were assessed. A retrospective estimation of 177 Lu-DOTATATE uptake in 33 patients was performed. An additional subgroup of 34 patients with paired samples from 3 tumour sites was identified. SSTR2 expression was assessed in corresponding tissue samples (n=102). Data regarding OS and non-surgical treatment were collected for both groups.Results SSTR2 expression did not vary between tumour sites but correlated among the patients’ lesions. Patients were grouped into Low SSTR2 or High SSTR2 depending on levels of SSTR2 expression. OS based on SSTR2 expression was not significantly different. However, PRRT treated patients with low SSTR2 expression received less additional treatment compared to patients with high SSTR2 expression and had a tendency towards higher 177 Lu-DOTATATE uptake.Conclusion The results from the present study suggest that low SSTR2 expression should not exclude patients from PRRT.