Retrospective evaluation of the predictive value of tumour burden at baseline [68 Ga]Ga-DOTA-TOC or -TATE PET/CT and tumour dosimetry in GEP-NET patients treated with PRRT.

Abstract

Purpose: There is a lack of validated imaging biomarkers for prediction of response to peptide receptor radionuclide therapy (PRRT). The primary objective was to evaluate if tumour burden at baseline PET/CT could predict treatment outcomes to PRRT with [¹⁷⁷Lu]Lu-DOTA-TATE. Secondary objectives were to evaluate if there was a correlation between tumour burden and mean tumour absorbed dose (AD) during first cycle, and if mean tumour AD or the relative change of tumour burden at first follow-up PET/CT could predict progression free survival (PFS) or overall survival (OS).

Methods: Patients with gastroenteropancreatic neuroendocrine tumour (GEP-NET) treated with [¹⁷⁷Lu]Lu-DOTA-TATE PRRT were retrospectively included. Tumour burden was quantified from [⁶⁸ Ga]Ga-DOTA-TOC/TATE PET/CT-images at baseline and first follow-up and expressed as; whole-body somatostatin receptor expressing tumour volume (SRETVwb), total lesion somatostatin receptor expression (TLSREwb), largest tumour lesion diameter and highest SUVmax. The relative change of tumour burden was evaluated in three categories. Mean tumour AD was estimated from the first cycle of PRRT. PFS was defined as time from start of PRRT to radiological or clinical progression. OS was evaluated as time to death. Kaplan Meier survival curves and log-rank test were used to compare PFS and OS between different groups.

Results: Thirty-one patients had a baseline PET/CT < 6 months before treatment and 25 had a follow-up examination. Median tumour burden was 132 ml (IQR 61-302) at baseline and 71 ml (IQR 36-278) at follow-up. Twenty-two patients had disease progression (median time to progression 17.2 months) and 9 patients had no disease progression (median follow-up 28.7 months). SRETVwb dichotomized by the median at baseline was not associated with longer PFS (p = 0.861) or OS (p = 0.937). Neither TLSREwb, largest tumour lesion or SUVmax showed significant predictive value. There was a moderately strong correlation, however, between SUVmax and mean tumour AD r = 0.705, p < 0.001, but no significant correlation between SRETVwb nor TLSREwb and mean tumour AD. An increase of SRETVwb, TLSREwb or largest tumour lesion at first follow-up PET/CT was significantly correlated with shorter PFS/OS.

Conclusion: Tumour burden at baseline showed no predictive value of PFS/OS after PRRT in this small retrospective study. An increase of tumour burden was predictive of worse outcome.