Somatostatin receptor expression in small cell lung cancer as a prognostic marker and a target for peptide receptor radionuclide therapy

Oncotarget. 2016 Apr 12;7(15):20033-40. doi: 10.18632/oncotarget.7706.

Abstract

Despite initial responsiveness to both chemotherapy and radiotherapy, small cell lung cancer (SCLC) commonly relapses within months. Although neuroendocrine characteristics may be difficult to demonstrate in individual cases, a relevant expression of somatostatin receptors (SSTR) on the cell surface has been described. We aimed to evaluate the prognostic value of SSTR-expression in advanced SCLC. We further examined pre-requisites for successful peptide receptor radionuclide therapy (PRRT). 21 patients with extensive stage SCLC were enrolled. All patients underwent positron emission tomography/computed tomography (PET/CT) with 68Ga-DOTATATE to select patients for SSTR-directed therapy. PET scans were visually and semi-quantitatively assessed and compared to SSTR2a and SSTR5 expression in biopsy samples. Peak standardized uptake values (SUVpeak) of tumors as well as tumor-to-liver ratios were correlated to progression-free (PFS) and overall survival (OS). In 4/21 patients all SCLC lesions were PET-positive. 6/21 subjects were rated "intermediate" with the majority of lesions positive, the remaining 11/21 patients were PET-negative. PET-positivity correlated well with histologic SSTR2a, but not with SSTR5 expression. Neither PET-positivity nor SUVpeak were predictors of PFS or OS. In 4 patients with intensive SSTR2a-receptor expression, PRRT was performed with one partial response and one stable disease, respectively. SSTR-expression as detected by 68Ga-DOTATATE-PET and/or histology is not predictive of PFS or OS in patients with advanced SCLC. However, in patients exhibiting sufficient tracer uptake, PRRT might be a treatment option given its low toxicity and the absence of effective alternatives.

Keywords: PET; molecular imaging; positron emission tomography; small cell lung cancer; somatostatin receptor.

MeSH terms

  • Adult
  • Aged
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / radiotherapy
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Organometallic Compounds / metabolism*
  • Positron Emission Tomography Computed Tomography
  • Prognosis
  • Radiopharmaceuticals / metabolism*
  • Receptors, Somatostatin / metabolism*
  • Small Cell Lung Carcinoma / diagnostic imaging
  • Small Cell Lung Carcinoma / metabolism*
  • Small Cell Lung Carcinoma / radiotherapy
  • Small Cell Lung Carcinoma / secondary

Substances

  • Organometallic Compounds
  • Radiopharmaceuticals
  • Receptors, Somatostatin
  • SSTR2 protein, human
  • somatostatin receptor 5
  • gallium Ga 68 dotatate