Abstract
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Introduction: Positron Emission Tomography (PET) using the somatostatin receptor 2 (SSTR2)-antagonist satoreotide trizoxetan (SSO120, previously OPS202) is a novel imaging modality for accurate staging of patients with small-cell lung cancer (SCLC). Here, we correlate uptake in PET imaging with SSTR2 expression in immunohistochemistry (IHC) and evaluate the prognostic value of 68Ga-SSO120 PET at initial staging of patients with SCLC.
Methods: We retrospectively included patients who underwent 68Ga-SSO120 PET/CT during initial diagnostic workup of SCLC. PET-positive tumor lesions were manually segmented using a 41-% threshold to delineate lesion boundaries. For patients with available tumor biopsies, SSTR2 expression in IHC was evaluated on a 4-level scale (0: negative, 1: 1-30%, 2: 30-70%, 3: ≥70%) and correlated with SUVmax/SUVpeak on a lesion level using Spearman’s rank correlation coefficient and ANOVA. Moreover, the whole-body SSTR2-expressing tumor volume (SSTR-TV) was calculated from all lesions per patient. SUVmax of the hottest lesion per patient, SSTR2 score in IHC, SSTR-TV, and Veterans Administration Lung Study Group (VALG) classification were analyzed for association with overall survival (OS) and progression-free survival (PFS) by univariate Cox regression (cut-off values were identified on data for best separation).
Results: We included 48 patients (26 female/22 male), mean age was 66 years. 44 patients had thoracic lymph node metastases (2 N1, 17 N3, and 25 N3 according to TNM classification), 18 patients had limited and 30 extensive disease according to VALG classification. Mean administered activity was 141 MBq and mean uptake time 63 min. In 34 patients with available pathological specimens, lesion SUVmax/SUVpeak showed a good correlation with histopathological SSTR2-expression (Spearman’s rho 0.73/0.70, p<0.001; ANOVA p<0.001). Significant association with shorter OS was shown for SSTR2 score ≥1 in IHC (median OS: 13.0 mos vs. not reached; HR: 0.25, 95%-CI: 0.07-0.85, p=0.016), extensive disease in VALG classification (13.0 vs. 16.2 mos; HR: 0.36, 95%-CI: 0.12-1.03, p=0.047) and SUVmax of the hottest lesion ≥28 (10.8 vs. 16.2 mos; HR: 0.35, 95%-CI: 0.13-0.89, p=0.022). For SSTR2-TV ≥250 mL, significance was not reached (10.8 vs. 16.2 mos; HR: 0.40, 95%-CI: 0.13-1.12, p=0.079). SSTR2 score ≥1 in IHC and SUVmax of the hottest lesion ≥33 showed significant correlation with shorter PFS (SSTR2 score ≥1 in IHC: median PFS 7.9 vs. 16.6 mos; HR: 0.28, 95%-CI: 0.10-0.75, p=0.007. SUVmax of the hottest lesion ≥33: 5.3 vs. 9.6 mos; HR: 0.40, 95%-CI: 0.16-1.03, p=0.048).
Conclusions: 68Ga-SSO120 PET is a tool for whole-body assessment of SSTR2-expression with SUVmax/SUVpeak correlating to histopathological SSTR2-expression. In patients with SCLC, SSTR2 expression assessed by 68Ga-SSO120 PET andby IHC as well as VALG classification were associated with shorter survival in univariate analyses. Investigation of a larger cohort with longer follow-up is warranted for multivariate analyses including other determinants of survival and to identify candidates for SSTR2-directed radionuclide therapy using 177Lu-SSO110.
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