In-Vivo Somatostatin-Receptor Expression in Small Cell Lung Cancer as a Prognostic Image Biomarker and Therapeutic Target

Simple Summary Despite novel targeted treatment options, small cell lung cancer (SCLC) still has a bad prognosis. However, as a relevant number of SCLC patients show a high expression of somatostatin receptors (SSTRs), SSTR-targeted radionuclide therapy (PRRT) may be a treatment option. Therefore, we investigated whether SSTR expression assessed in positron emission tomography (PET) has prognostic value. In patients with adequate PET uptake, PRRT was performed, and the outcome was investigated. We found that SSTR-targeted PET, although not a prognostic tool for outcome, is an important tool for treatment decision. In some patients, PRRT can be a promising treatment option as a second or third line treatment of SCLC. Background: Given the dismal prognosis of small cell lung cancer (SCLC), novel therapeutic targets are urgently needed. We aimed to evaluate whether SSTR expression, as assessed by positron emission tomography (PET), can be applied as a prognostic image biomarker and determined subjects eligible for peptide receptor radionuclide therapy (PRRT). Methods: A total of 67 patients (26 females; age, 41-80 years) with advanced SCLC underwent SSTR-directed PET/computed tomography (somatostatin receptor imaging, SRI). SRI-avid tumor burden was quantified by maximum standardized uptake values (SUVmax) and tumor-to-liver ratios (T/L) of the most intense SCLC lesion. Scan findings were correlated with progression-free (PFS) and overall survival (OS). In addition, subjects eligible for SSTR-directed radioligand therapy were identified, and treatment outcome and toxicity profile were recorded. Results: On a patient basis, 36/67 (53.7%) subjects presented with mainly SSTR-positive SCLC lesions (>50% lesions positive); in 10/67 patients (14.9%), all lesions were positive. The median SUVmax was found to be 8.5, while the median T/L was 1.12. SRI-uptake was not associated with PFS or OS, respectively (SUVmax vs. PFS, & rho; = 0.13 with p = 0.30 and vs. OS, & rho; = 0.00 with p = 0.97; T/L vs. PFS, & rho; = 0.07 with p = 0.58 and vs. OS, & rho; = -0.05 with p = 0.70). PRRT was performed in 14 patients. One patient succumbed to treatment-independent infectious complications immediately after PRRT. In the remaining 13 subjects, disease control was achieved in 5/13 (38.5%) with a single patient achieving a partial response (stable disease in the remainder). In the sub-group of responding patients, PFS and OS were 357 days and 480 days, respectively. Conclusions: SSTR expression as detected by SRI is not predictive of outcome in patients with advanced SCLC. However, it might serve as a therapeutic target in selected patients.

Automated summary

Despite the availability of novel targeted treatment options, small cell lung cancer (SCLC) still has a poor prognosis. This study aimed to evaluate the prognostic value of somatostatin receptor (SSTR) expression assessed by positron emission tomography (PET) and investigate the efficacy of SSTR-targeted radionuclide therapy (PRRT). The results showed that SSTR-targeted PET is not a prognostic tool for outcome in SCLC patients, but it can be an important tool for treatment decision. PRRT may be a promising treatment option for some patients with SCLC as a second or third line treatment.