High clinical and morphologic response using Y-DOTA-octreotate sequenced with Lu-DOTA-octreotate induction peptide receptor chemoradionuclide therapy (PRCRT) for bulky neuroendocrine tumours.

Purpose: Bulky disease is an adverse prognostic factor for Lu-DOTA-octreotate (Lu-DOTATATE) peptide receptor radionuclide therapy (PRRT). Y-DOTA-octreotate (Y-DOTATATE) has theoretical advantages in this setting but may less effectively treat co-existent smaller deposits and have higher toxicity than Lu-DOTATATE. The aim of this study was to assess the efficacy and safety of using these agents sequentially.

Methods: We reviewed patients (pts) with at least one lesion of a transaxial diameter >4 cm who completed 1-2 cycles of Y-DOTATATE followed by 2-3 cycles of Lu-DOTATATE, with treatment empirically adapted to disease size and burden in individual patients. Data collected included morphological and molecular imaging response, toxicity, and progression-free and overall survival.

Results: Twenty-six pts (17 men; aged 27-74 years) received a median cumulative activity of 6.5 GBq Y-DOTATATE, and 21 GBq Lu-DOTATATE. All but one received radiosensitising chemotherapy. Adverse prognostic factors included ENETS grade 2 or 3 in 58 %, and FDG-avid disease in 73 %. Nineteen pts treated for progressive disease had stabilisation (37 %) or regression on CT (42 % partial response, 21 % minor response), with a mean 59 % (8-99 %) reduction in disease burden. All seven pts treated for uncontrolled symptoms reported improvement during PRRT with 4/7 having complete symptom resolution at 3 months. Eight patients had grade 3/4 lymphopaenia, and two patients grade 3/4 thrombocytopaenia without significant hepatic or renal toxicity. Median survival was not reached after a median follow-up of 35 months. Median progression-free survival was 33 months.

Conclusion: PRCRT with Y -DOTATATE followed by Lu-DOTATATE in individualised regimens achieved high clinical and morphological response in patients with bulky tumours. Despite lack of a control arm, the efficacy of this treatment approach appears higher than reported results with either agent used alone or other approved treatments, particularly given the adverse prognostic features of this cohort.