Somatostatin Receptor-Directed Theranostics in Esthesioneuroblastoma

Abstract

Background: We aim to report on somatostatin receptor (SSTR)-targeted molecular imaging and therapy in patients with advanced esthesioneuroblastoma (ENB).

Patients and methods: Five patients with ENB [Kadish stage D in 5/5 (100%); Hyams grade 2 in 2/5 (40%), grade 3 in 2/5 (40%), undetermined in 1/5 (20%)] underwent SSTR-directed PET/CT. We quantified SSTR-avid tumor volume (TV), maximum SUV (SUV max ), and target-to-background ratios (TBR). Based on imaging, peptide receptor radionuclide therapy (PRRT) along with dosimetry was also conducted. We recorded nephrotoxicity and hematotoxicity, including estimated glomerular filtration rate (eGFR), hemoglobin, leukocytes, and thrombocytes at baseline and after the last treatment cycle. We determined adverse events following Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Response and progression-free survival (PFS) was also evaluated.

Results: All 5 patients were rated positive on SSTR-PET/CT. On a lesion-based level, we identified 32 SSTR-avid tumor sites with a median TV of 11.7±10.8 and SUV max of 24.3±12.8. TBR was 19.8±9.7, indicating excellent image contrast. After median 4 (range, 2-6) cycles with a median of 7.7 GBq per cycle per patient, we observed no CTCAE grade 3 or 4 toxicity for leukocytes and thrombocytes and no significant CTCAE events for renal function. One patient (20%), however, developed reversible grade 3 anemia. Up to 11.8 Gy in tumor lesions were achieved. Partial response was recorded in 3/5 (60%), stable disease in 1/5 (20%), and progressive disease in 1/5 (20%). The median PFS was 29 weeks.

Conclusions: SSTR-directed PET provided high image contrast in ENB, suggesting good read-out capabilities in this tumor type. PRRT was also feasible, along with an acceptable safety profile, thereby rendering SSTR-targeted theranostics a potential treatment option in advanced disease.

Keywords: ENB; PET; PET/CT; SSTR; [68Ga]Ga-DOTATOC; esthesioneuroblastoma; somatostatin receptor.

FIGURE 1

A 59-year-old man with esthesioneuroblastoma, classified as Kadish grade D and Hyams grade 3 with partial response upon first restaging (after 2 cycles of PRRT) and second restaging (after 2 more treatment cycles). Maximum intensity projections of SSTR-directed PET/CT and transaxial views are displayed on the left (at baseline before therapy), middle (restaging after 2 cycles of PRRT) and right (restaging after 2 more cycles). Posttherapeutic whole-body (WB) planar scintigraphy between restagings in the anterior views are also displayed (inserts). Left: at baseline, the patient presented with SSTR-positive pulmonal and lymph node lesions (arrows). Middle: after 2 cycles of PRRT, the patient showed partial response with a decrease in the size of lesions on SSTR-targeted PET/CT (arrows). Right: after 2 more cycles, the subject presented with a further decline of target lesions upon restaging with PET/CT (arrows). WB planar views right after the first and second cycles (insert, left) showed intense uptake after injection of the ¹⁷⁷Lu-labeled, SSTR-positive radiotherapeutic, which further decline of uptake after the third and fourth cycle (insert, right), which was most likely due to a decrease in tumor size under treatment.