Early prediction of tumour response to PRRT

Summary

[¹⁷⁷Lu-DOTA0, Tyr3]-octreotate (¹⁷⁷Lu-octreotate) in peptide receptor radionuclide therapy (PRRT) offers direct intra-therapeutic dosimetry. The aim of this study was to compare tumour and non-tumour parameters and assess intra-individual variations. Patients, methods: Retrospective analysis of 53 consecutive PRRT treatment cycles (mean activity of 7.53 ± 0.46 GBq ¹⁷⁷Lu-octreotate, intended four cycles at intervals of 10–14 weeks, standard nephroprotection) in 27 GEP NET patients. Extended planar dosimetry with serial wholebody imaging on selected, non-superimposed tumour and non-tumour regions; liver (LM), bone (BM), and other (OM) metastases. The per-cycle variation was compared with posttreatment response (CT/MRI three months post-treatment, modified SWOG criteria). Results: Residence time in tumor lesions (133–147 h) exceeded that in kidneys (93 h). Tumour-to-kidney absorbed dose ratios ranged from 14 to 28 (LM, BM, OM). Intra-individual per-cycle dose variation was insignificant for kidneys, but significant for metastases (LM, BM, and OM; p < 0.05). The mean per-cycle decrease of tumour absorbed dose (_D/A0[%]) was linked to morphologic response after PRRT. A mean decrease of >20% was predictive of a partial or minor remission in all 11 evaluable patients, while absent significant dose reduction indicated stable or progressive disease in 4/5 patients. The dose decrease was unrelated to volume effects and also observed for BM. Conclusion: Besides confirmation of a favourable tumour-to-kidney parameter relation for ¹⁷⁷Lu-octreotate, stepwise intra-lesional comparison seems to imply a prognostic impact of tumor dosimetry: The early per-cycle change _D/A0 between treatment cycles may predict the outcome after PRRT. Larger studies are needed to confirm this finding.

Zusammenfassung

[¹⁷⁷Lu-DOTA0, Tyr3]-Octreotat (¹⁷⁷Lu-octreotate) bei der Peptid-Radiorezeptortherapie (PRRT) bietet eine direkte Form der intra-therapeutischen Dosimetrie. Das Ziel der Studie war der Vergleich von Tumor- und Normal-gewebe-Parametern und die Untersuchung intra-individueller Variationen. Patienten, Methodik: Retrospektive Analyse von 53 konsekutiven PRRT-Behandlungszyklen (mottler Aktivität 7.53 ± 0.46 GBq ¹⁷⁷Lu-octreotate, intendierte vier Zyklen in 10- bis 14-wöchigen Intervallen, Standard-Nephroprotektion) in 27 GEP-NET-Patienten. Erweiterte planare Dosimetrie mittels serieller Ganzkörperbildgebung von selektierten, nicht-überlagerten Tumorund Nichttumor-Regionen: Leber- (LM), Knochen- (BM) und anderer (OM) Metastasen. Die Zyklus-bezogene Variation wurde mit dem Therapieansprechen (CT/MRT 3 Monate post-PRRT, modifizierte SWOG Kriterien) verglichen. Ergebnisse: Die Residenzzeit der Tumorläsionen (133–147 h) übertraf die der Nieren (93 h). Die Herddosis-Ratio Tumor-zu-Niere lag zwischen 14 und 28 (LM, BM, OM). Die intra-individuelle Variation der Herddosen zwischen den Zyklen war nicht signifikant für die Nieren, aber signifikant für die Metastasen (LM, BM und OM; p < 0.05). Die mittlere Zyklus-assoziierte Abnahme der Tumor-Herddosis (_D/A0[%]) korrelierte mit dem morphologischen Ansprechen nach PRRT. Eine mittlere Abnahme von >20% war prädiktiv für eine Teilremission in den 11 auswertbaren Patienten, während eine fehlende signifikante Herddosis-Reduktion einen stabilen oder progredienten Verlauf in 4/5 Patienten vorher sagte. Die Dosisabnahme war unabhängig von Volumeneffekten und auch bei Knochenmetastasen zu beobachten. Schlussfolgerung: Neben der Bestätigung einer günstigen Relation „Tumor-zu-Niere“ verschiedener Parameter für ¹⁷⁷Lu-octreotate zeigte der schrittweise intra-läsionale Vergleich in der Tumordosimetrie einen prädiktiven Einfluss: Die frühe Zyklus-bezogene Veränderung _D/A0 zwischen den Behandlungszyklen vermag das Ergebnis nach PRRT vorherzusagen. Größere Studien müssen diese Beobachtung bestätigen.

Keywords

Gastroenteropancreatic neuroendocrine tumours - dosimetry - peptide receptor radionuclide therapy - ¹⁷⁷Lu-DOTA octreotate - tumour response

Schlüsselwörter

Gastro-enteropankreatische Tumoren - Dosimetrie - Peptid-Radiorezeptortherapie - ¹⁷⁷Lu-DOTA-Octreotat - Therapie-Ansprechen

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