The relationship between tumour dosimetry, response, and overall survival in patients with unresectable Neuroendocrine Neoplasms (NEN) treated with (177)Lu DOTATATE (LuTate)

ABSTRACT: Peptide Receptor Radionuclide Therapy (PRRT) delivers targeted radiation to Somatostatin Receptor (SSR) expressing Neuroendocrine Neoplasms (NEN). We sought to assess the predictive and prognostic implications of tumour dosimetry with respect to response by (68) Ga DOTATATE (GaTate) PET/CT molecular imaging tumour volume of SSR (MITV(SSR)) change and RECIST 1.1, and overall survival (OS). METHODS: Patients with gastro-entero-pancreatic (GEP) NEN who received LuTate followed by quantitative SPECT/CT (Q-SPECT/CT) the next day (Jul 2010 to Jan 2019) were retrospectively reviewed. Single time-point (STP) lesional dosimetry was performed for each cycle using population-based pharmacokinetic modelling. MITV(SSR) and RECIST 1.1 were measured at 3-months post PRRT. RESULTS: Median of 4 PRRT cycles were administered to 90 patients (range 2–5 cycles; mean 27.4 GBq cumulative activity; mean 7.6 GBq per cycle). 68% received at least one cycle with radiosensitising chemotherapy (RSC). RECIST 1.1 partial response was 24%, with 70% stable and 7% progressive disease. Cycle 1 radiation dose in measurable lesions was associated with local response (odds ratio 1.5 per 50 Gy [95% CI: 1.1–2.0], p = 0.002) when adjusted by tumour grade and RSC. Median change in MITV(SSR) was -63% (interquartile range -84 to -29), with no correlation with radiation dose to the most avid lesion on univariable or multivariant analyses (5.6 per 10 Gy [95% CI: -1.6, 12.8], p = 0.133). OS at 5-years was 68% (95% CI: 56–78%). Neither baseline MITV(SSR) (hazard ratio 1.1 [95% CI: 1.0, 1.2], p = 0.128) nor change in baseline MITV(SSR) (hazard ratio 1.0 [95% CI: 1.0, 1.1], p = 0.223) were associated with OS when adjusted by tumour grade and RSC but RSC was (95% CI: 0.2, 0.8, p = 0.012). CONCLUSION: Radiation dose to tumour during PRRT was predictive of radiologic response but not survival. Survival outcomes may relate to other biological factors. There was no evidence that MITV(SSR) change was associated with OS, but a larger study is needed. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-023-06257-6.