Functional imaging in neuroendocrine tumors: assessment of molecular heterogeneity using [68Ga]Ga-DOTA-TOC and [18F]FDG PET/CT.

OBJECTIVE: The aim of the study was evaluate the diagnostic performance of [68Ga]Ga-DOTA-TOC and [18F]FDG PET/CT in patients with histologically proven neuroendocrine tumors (NETs), as well as the correlation of the visualized findings with the tumor grade. MATERIAL AND METHODS: We included 50 patients with NETs who underwent both [68Ga]Ga-DOTA-TOC and [18F]FDG PET/TC. The pooled sensitivity of both scans was compared, as well as [68Ga]Ga-DOTA-TOC and [18F]FDG for each tumor grade (grade 1/G1, grade 2/G2 and grade 3/G3). Also, the sensitivity of [68Ga]Ga-DOTA-TOC and [18F]FDG as a function of the continuous variable Ki-67 was investigated. Finally, the number of lesions detected by both PET radiopharmaceuticals for each tumor grade was compared. RESULTS: The pooled sensitivity of both PET/CT (96%) was higher than [68Ga]Ga-DOTA-TOC (84%) and [18F]FDG (44%) separately, with statistically significant differences. The sensitivity of [68Ga]Ga-DOTA-TOC was higher than [18F]FDG in both G1 (p = 0.004) and G2 (p < 0.001). In G3 the performance of both scans detected disease in 100% of this subgroup. The sensitivity of [68Ga]Ga-DOTA-TOC and [18F]FDG PET/CT correlated significantly with the Ki-67 proliferative index. In G2 patients the number of lesions detected with [68Ga]Ga-DOTA-TOC was higher than [18F]FDG. CONCLUSIONS: The performance of both PET/CT, particularly in G2 and G3, demonstrates the molecular heterogeneity of metastatic NETs and contributes to the selection of a more appropriate treatment, particularly in those high-grade patients who may benefit from radionuclide therapy (PRRT).

Papel de los factores inflamatorios sistémicos en los tumores neuroendocrinos gastroenteropancreáticos (TNE-GEP) tratados con péptidos marcados con radionúclidos (PRRT): de la biología a la teragnosis / Role of systemic inflammatory factors in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with peptide receptor radionuclide therapy (PRRT): From biology to theragnosis

Objetivo Los índices inflamatorios sistémicos se han validado como indicadores de inflamación sistémica como marcadores predictivos de mal pronóstico para diversas enfermedades oncológicas. Sin embargo, se desconoce el impacto pronóstico de los marcadores de inflamación sistémica en pacientes con tumores neuroendocrinos gastroenteropancreáticos (TNE-GEP) tratados con péptidos marcados con radionúclidos (PRRT). Métodos Realizamos un estudio observacional, retrospectivo, multicéntrico de 40 pacientes con TNEs-GEP y TNE de origen desconocido tratados con PRRT entre el 2016 y el 2020. Los marcadores inflamatorios sistémicos se calcularon de la siguiente manera: relación neutrófilos a linfocitos (NLR)=recuento de neutrófilos/recuento de linfocitos, relación de monocitos a linfocitos (MLR)=recuento de monocitos/recuento de linfocitos, relación de plaquetas a linfocitos (PLR)=recuento de plaquetas/recuento de linfocitos, relación de albúmina a linfocitos (ALR)=niveles de albúmina/recuento de linfocitos y relación derivada de neutrófilos a linfocitos (dNLR)=recuento de neutrófilos/(recuento de leucocitos – recuento de neutrófilos). Se utilizaron datos analíticos basales pretratamiento y después de la segunda dosis para el cálculo de los distintos índices. Resultados La mediana de edad fue de 63 años (rango 41-85), el 55% eran hombres. Los valores de corte de referencia para NLR fueron 2,61, para MLR 0,31, para PLR 110,14, para ALR 2,39 y para dNLR 1,71. Los valores de corte después de la segunda dosis fueron, para NLR 2,3, para MLR 0,3, para PLR 131,61, ALR 4,16 y dNLR 1,48. La mediana de la sobrevivencia libre de progresión (SLP) fue de 21,7 meses (IC del 95%: 10,7-32,8 m) y la supervivencia global (SG) fue de 32,1 meses (IC del 95%: 19,6-44,7 m), la SLP fue más corta en pacientes con NLR elevado (p=0,001), ALR (0,03) y dNLR (p=0,001) en el análisis basal. La tasa de control de enfermedad (DCR) fue del 81% y la tasa de respuesta objetiva (ORR) del 18% (AU)

Aim Systemic inflammatory factors have been validated as indicators of ongoing systemic inflammation that could be predictive markers of poor prognosis for oncological outcomes. However, the prognostic impact of systemic inflammation markers is unknown in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with peptide receptor radionuclide therapy (PRRT). Methods We conducted an observational, retrospective, multicentric study of 40 patients with GEP or unknown origin NETs treated with PRRT between 2016 and 2020. The systemic inflammatory markers were calculated as follows: neutrophil to lymphocyte ratio (NLR)=neutrophil count/lymphocyte count, monocyte to lymphocyte ratio (MLR)=monocyte count/lymphocyte count, platelet to lymphocyte ratio (PLR)=platelet count/lymphocyte count, albumin to lymphocyte ratio (ALR)=albumin levels/lymphocyte count and derived Neutrophil to Lymphocyte ratio (dNLR)=neutrophil count/(leucocytes count – neutrophils count). Baseline analysis and after the second dose were used for the calculation of different ratios. Results The median age was 63 years (range 41–85), 55% were male. The baseline cut-off values for NLR were 2.61, for MLR 0.31, for PLR 110.14, for ALR 2.39 and for dNLR 1.71. The cut-off values after the 2° dose were, for NLR 2.3, for MLR 0.3, for PLR 131.61, ALR 4.16, and dNLR 1.48. Median progression-free survival (PFS) was 21.7 months (95% CI 10.7–32.8 months) and overall survival (OS) was 32.1 months (95% CI 19.6–44.7 months), PFS was shorter in patients with elevated NLR (P=0.001), ALR (0.03), and dNLR (P=0.001) in baseline analysis. DCR was 81% and ORR 18%. Conclusions In GEP or unknown origin NETs treated with PRRT, we have identified the predictive and prognostic impact of baseline systemic inflammatory factors (AU)

Role of systemic inflammatory factors in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with peptide receptor radionuclide therapy (PRRT): From biology to theragnosis.

AIM: Systemic inflammatory factors have been validated as indicators of ongoing systemic inflammation that could be predictive markers of poor prognosis for oncological outcomes. However, the prognostic impact of systemic inflammation markers is unknown in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with peptide receptor radionuclide therapy (PRRT). METHODS: We conducted an observational, retrospective, multicentric study of 40 patients with GEP or unknown origin NETs treated with PRRT between 2016 and 2020. The systemic inflammatory markers were calculated as follows: neutrophil to lymphocyte ratio (NLR)=neutrophil count/lymphocyte count, monocyte to lymphocyte ratio (MLR)=monocyte count/lymphocyte count, platelet to lymphocyte ratio (PLR)=platelet count/lymphocyte count, albumin to lymphocyte ratio (ALR)=albumin levels/lymphocyte count and derived Neutrophil to Lymphocyte ratio (dNLR)=neutrophil count/(leucocytes count - neutrophils count). Baseline analysis and after the second dose were used for the calculation of different ratios. RESULTS: The median age was 63 years (range 41-85), 55% were male. The baseline cut-off values for NLR were 2.61, for MLR 0.31, for PLR 110.14, for ALR 2.39 and for dNLR 1.71. The cut-off values after the 2° dose were, for NLR 2.3, for MLR 0.3, for PLR 131.61, ALR 4.16, and dNLR 1.48. Median progression-free survival (PFS) was 21.7 months (95% CI 10.7-32.8 months) and overall survival (OS) was 32.1 months (95% CI 19.6-44.7 months), PFS was shorter in patients with elevated NLR (p=0.001), ALR (0.03), and dNLR (p=0.001) in baseline analysis. DCR was 81% and ORR 18%. CONCLUSIONS: In GEP or unknown origin NETs treated with PRRT, we have identified the predictive and prognostic impact of baseline systemic inflammatory factors.