CXCR4-directed imaging and therapy of desmoplastic small round cell tumors

Ziel/Aim Desmoplastic small round cell tumor (DSRCT) is a rare, but highly aggressive malignancy, which most commonly occurs in young male adolescents and primarily involves the abdominal cavity. A specific gene fusion (EWSR1-WT1) is characterizing this disease. Despite the presence of multiple druggable targets in the downstream of the EWSR1-WT1 fusion (e.g. VEGF, EGFR, IGF-1), prognosis is still poor. The aim of this study was to compare the diagnostic accuracy of [⁶⁸Ga]CXCR4 PET/CT and [¹⁸F]FDG PET/CT and to evaluate the feasibility of a CXCR4-based endoradiotherapy.

Methodik/Methods This retrospective analysis included nine patients with dual tracer imaging ([¹⁸F]FDG and [⁶⁸Ga]Ga-CXCR4). In all patients, the pattern of uptake in both tracers was assessed visually and the uptake in DSRCT lesions (SUV_max, SUV_peak) was quantified and compared. In five patients with progressive disease, CXCR4-based endoradiotherapy was applied after individual dosimetry. One patient additionally received high dose chemotherapy with stem cell rescue. Response was assessed using RECIST 1.1 criteria. In addition, overall survival and side effects were assessed.

Ergebnisse/Results On a lesion basis, both tracers showed a moderate (SUV_max: r = 0.29, p ≤ 0.05; SUV_peak: r = 0.55, p ≤ 0.001) correlation. Mean SUV_max and SUV_peak were significantly higher for ¹⁸F-FDG than for ⁶⁸Ga-CXCR4 (SUV_max: 9.9 ± 4.3 vs. 8.1 ± 3.4, p ≤ 0.01; SUV_peak: 6.4 ± 3.4 vs. 5.0 ± 2.1, p ≤ 0.01). After therapy, mean SUV_max and SUV_peak in ⁶⁸Ga-CXCR4 PET/CT significantly declined (SUV_max: 7.4 ± 3.1 vs. 8.7 ± 2.2, p ≤ 0.05; SUV_peak: 4.7 ± 1.9 vs. 5.7 ± 1.7, p ≤ 0.05). At FDG PET/CT, mean SUV_max and SUV_peak of DSRCT lesions significantly dropped (SUV_max: 7.1 ± 4.2 vs. 11.6 ± 4.3, p ≤ 0.001; SUV_peak: 5.2 ± 2.9 vs. 7.6 ± 3.7, p ≤ 0.001). No severe side effects occurred after CXCR4-based endoradiotherapy. One patient achieved a disease stabilization for 143 days, while four patients showed progressive disease. Median OS was 143 days (range 53-282).

Schlussfolgerungen/Conclusions DSRCT exhibits strong CXCR4-expression. CXCR4-based imaging seems to deliver comparable diagnostic information as compared to FDG PET/CT. CXCR4-based endoradiotherapy seems feasible with few acute side effects and warrants further investigation.

Publikationsverlauf

Artikel online veröffentlicht:
08. April 2021