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.

Impact of risk factors on the efficacy and complications of ultrasound-guided percutaneous liver biopsy of space-occupying lesions.

INTRODUCTION: Ultrasound-guided percutaneous liver biopsy is considered the technique of choice for the histological diagnosis of space-occupying lesions, given its high level of safety and diagnostic performance. However, since it is an invasive diagnostic procedure, complications can occur. Various clinical and radiological parameters have been analysed as factors related with the efficacy of the technique or with its complications; however, the results have been contradictory. Thus, we aimed to evaluate the impact of various risk factors on the efficacy and complications of ultrasound-guided percutaneous liver biopsy in the diagnosis of space-occupying lesions in ordinary clinical practice. MATERIAL AND METHODS: This retrospective observational study included all patients who underwent real-time ultrasound-guided percutaneous biopsies of space-occupying liver lesions with the free-hand technique between December 2012 and February 2018 in the diagnostic imaging department at the Hospital Clínico Universitario de Santiago de Compostela. We analysed the following risk factors: location of the lesion in upper liver segments (II, IVa, VII, or VIII); proximity to the liver capsule, distance from the skin >100mm, interposition of osseus or vascular structures, inability to go through healthy parenchyma, and lack of patient cooperation during the procedure. Efficacy was analysed in terms of the number of cylinders obtained and the percentage of adequate biopsies; safety was analysed in terms of the percentage of complications, which were classified as major or minor. RESULTS: We included 295 biopsies in 278 patients (median age, 69 years; 64.1% male; 44.7% had prior neoplasms). In 61.4%, the biopsy was indicated for the initial diagnosis; 82.4% of biopsies were done in hospitalised patients, and 65% of the lesions were located in the right liver lobe. The median number of cylinders obtained was 3 (range 1-6); 91.2% of the biopsies were adequate and 92.2% were considered clinically useful. These percentages did not differ significantly according to the presence of risk factors. Complications occurred in 10 (3.4%) patients. Complications were considered major in 3 (0.9%) patients (2 (0.6%) bleeding complications and 1 (0.3%) infectious complication) and minor in 7 (2.4%). The percentage of complications was significantly higher in patients who did not cooperate during the procedure (P=.04). CONCLUSIONS: Ultrasound-guided percutaneous liver biopsy is an efficacious and safe technique for the histological diagnosis of space-occupying liver lesions. Our results confirm the increased rate of complications when patients fail to cooperate during the procedure.

Impacto de los factores de riesgo en la eficacia y complicaciones de la biopsia hepática percutánea ecoguiada de lesiones ocupantes de espacio / Impact of risk factors on the efficacy and complications of ultrasound-guided percutaneous liver biopsy of space-occupying lesions

Introducción: La biopsia hepática percutánea ecoguiada se considera la técnica de elección para el diagnóstico histológico de las lesiones ocupantes de espacio (LOE), dada su elevada seguridad y rentabilidad diagnóstica. Sin embargo, al tratarse de una técnica de diagnóstico invasiva, no se encuentra exenta de complicaciones. Diversos parámetros clínico-radiológicos han sido analizados como factores relacionados con la eficacia o complicaciones, con resultados contradictorios. Por todo ello, el objetivo de nuestro estudio es evaluar el impacto de diversos factores de riesgo en la eficacia y complicaciones de la biopsia hepática percutánea ecoguiada en el diagnóstico de LOE, en el ámbito de la práctica clínica habitual. Material y métodos: Llevamos a cabo un estudio observacional, retrospectivo, unicéntrico de pacientes sometidos a biopsia hepática percutánea ecoguiada en tiempo real con técnica de manos libres para el diagnóstico de LOE, realizadas en el Servicio de Radiodiagnóstico del Hospital Clínico Universitario de Santiago de Compostela entre diciembre 2012 y febrero 2018. Seleccionamos como factores de riesgo: la localización de la LOE en los segmentos hepáticos superiores (II, IVa, VII y VIII), la proximidad a la cápsula hepática, la distancia entre piel y LOE mayor de 100mm, la interposición de estructuras óseas o vasculares, la incapacidad para atravesar parénquima sano o la falta de colaboración del paciente durante el procedimiento. La eficacia fue analizada en términos de número de cilindros extraídos y porcentaje de biopsias satisfactorias; y la seguridad, en términos de porcentaje de complicaciones presentadas, clasificándolas, a su vez, en complicaciones mayores y menores. Resultados: Se incluyeron 295 biopsias de 278 pacientes. La mediana de edad fue de 69 años, el 64,1% eran varones y el 44,7% tenía una neoplasia previa.(AU)

Introduction: Ultrasound-guided percutaneous liver biopsy is considered the technique of choice for the histological diagnosis of space-occupying lesions, given its high level of safety and diagnostic performance. However, since it is an invasive diagnostic procedure, complications can occur. Various clinical and radiological parameters have been analyzed as factors related with the efficacy of the technique or with its complications; however, the results have been contradictory. Thus, we aimed to evaluate the impact of various risk factors on the efficacy and complications of ultrasound-guided percutaneous liver biopsy in the diagnosis of space-occupying lesions in ordinary clinical practice. Material and methods: This retrospective observational study included all patients who underwent real-time ultrasound-guided percutaneous biopsies of space-occupying liver lesions with the free-hand technique between December 2012 and February 2018 in the diagnostic imaging department at the Hospital Clínico Universitario de Santiago de Compostela. We analyzed the following risk factors: location of the lesion in upper liver segments (II, IVa, VII, or VIII); proximity to the liver capsule, distance from the skin > 100mm, interposition of osseus or vascular structures, inability to go through healthy parenchyma, and lack of patient cooperation during the procedure. Efficacy was analyzed in terms of the number of cylinders obtained and the percentage of adequate biopsies; safety was analyzed in terms of the percentage of complications, which were classified as major or minor. Results: We included 295 biopsies in 278 patients (median age, 69 years; 64.1% male; 44.7% had prior neoplasms). In 61.4%, the biopsy was indicated for the initial diagnosis; 82.4% of biopsies were done in hospitalized patients, and 65% of the lesions were located in the right liver lobe.(AU)

Impact of risk factors on the efficacy and complications of ultrasound-guided percutaneous liver biopsy of space-occupying lesions. / Impacto de los factores de riesgo en la eficacia y complicaciones de la biopsia hepática percutánea ecoguiada de lesiones ocupantes de espacio.

INTRODUCTION: Ultrasound-guided percutaneous liver biopsy is considered the technique of choice for the histological diagnosis of space-occupying lesions, given its high level of safety and diagnostic performance. However, since it is an invasive diagnostic procedure, complications can occur. Various clinical and radiological parameters have been analyzed as factors related with the efficacy of the technique or with its complications; however, the results have been contradictory. Thus, we aimed to evaluate the impact of various risk factors on the efficacy and complications of ultrasound-guided percutaneous liver biopsy in the diagnosis of space-occupying lesions in ordinary clinical practice. MATERIAL AND METHODS: This retrospective observational study included all patients who underwent real-time ultrasound-guided percutaneous biopsies of space-occupying liver lesions with the free-hand technique between December 2012 and February 2018 in the diagnostic imaging department at the Hospital Clínico Universitario de Santiago de Compostela. We analyzed the following risk factors: location of the lesion in upper liver segments (II, IVa, VII, or VIII); proximity to the liver capsule, distance from the skin > 100mm, interposition of osseus or vascular structures, inability to go through healthy parenchyma, and lack of patient cooperation during the procedure. Efficacy was analyzed in terms of the number of cylinders obtained and the percentage of adequate biopsies; safety was analyzed in terms of the percentage of complications, which were classified as major or minor. RESULTS: We included 295 biopsies in 278 patients (median age, 69 years; 64.1% male; 44.7% had prior neoplasms). In 61.4%, the biopsy was indicated for the initial diagnosis; 82.4% of biopsies were done in hospitalized patients, and 65% of the lesions were located in the right liver lobe. The median number of cylinders obtained was 3 (range 1-6); 91.2% of the biopsies were adequate and 92.2% were considered clinically useful. These percentages did not differ significantly according to the presence of risk factors. Complications occurred in 10 (3.4%) patients. Complications were considered major in 3 (0.9%) patients (2 (0.6%) bleeding complications and 1 (0.3%) infectious complication) and minor in 7 (2.4%). The percentage of complications was significantly higher in patients who did not cooperate during the procedure (p=0.04). CONCLUSIONS: Ultrasound-guided percutaneous liver biopsy is an efficacious and safe technique for the histological diagnosis of space-occupying liver lesions. Our results confirm the increased rate of complications when patients fail to cooperate during the procedure.

Efficacy and safety of trifluridine/tipiracil in third-line and beyond for the treatment of patients with metastatic colorectal cancer in routine clinical practice: patterns of use and prognostic nomogram.

INTRODUCTION: Trifluridine/tipiracil combination has shown a benefit over placebo in the treatment of patients with chemorefractory metastatic colorectal cancer (mCRC). We evaluated the efficacy and safety of this combination in the real-life setting at eight Galician centers in Spain. PATIENTS AND METHODS: This is a retrospective study of a cohort of patients with mCRC in treatment with trifluridine/tipiracil within usual clinical practice who have been previously treated or are not considered candidates for treatment with available therapies. RESULTS: A total of 160 mCRC patients were included. Our data showed that 11.9% of patients achieved disease control. Median progression-free survival was 2.75 months; at 5.66 months follow-up, median overall survival was 7.94 months. Asthenia and neutropenia (48.1% both) were the most frequent adverse events. Overall survival was lower in patients with ECOG 2, multiple metastatic sites, platelets count 350,000/µl, alkaline phosphatase > 500 IU/l, and carcinoembryonic antigen > 10 ng/ml. CONCLUSION: The results of this study confirm the efficacy and safety of trifluridine/tipiracil in chemorefractory mCRC patients. However, patients in clinical practice differ from patients in clinical trials. Due to this, prognostic factors have special importance to offer the best therapeutic approach.

Adjuvant treatment with infusional 5-fluorouracil in high risk adenocarcinoma of the stomach or gastroesophageal junction

Purpose. In high risk gastric and gastroesophageal adenocarcinoma, adjuvant radiochemotherapy with 5-fluorouracil bolus became a standard adjuvant treatment, showing significant improvement in overall survival after surgery, although with substantial toxicity. We explored the efficacy and toxicity of a modified 5-fluorouracil continuous infusion scheme. Methods. We conducted an observational retrospective study in our centre. Gastric/gastroesophageal junction adenocarcinoma patients were treated with a schedule consisting in four infusions of bolus 5-fluorouracil 400 mg/m2 iv with leucovorin 200 mg/m2 iv and 1200 mg/m2 in 46-hour infusion of 5-fluorouracil (D’Gramont scheme), followed by concomitant radiochemotherapy (45 Gy in 25 fractions of 1.8 Gy) with 5-fluorouracil continuously infusion 225 mg/m2/day and four additional infusions of chemotherapy one month after complete radiochemotherapy. Results. Between January 2007 and December 2013, 55 patients received a mean of 3.16 bi-weekly adjuvant infusions followed by 4.6 weeks of continuous treatment concurrent with radiotherapy and 3.72 bi-weekly infusions after radiotherapy treatment. During adjuvant treatment, grade III toxicity was mostly haematologic, while gastrointestinal and cutaneous toxicity was predominant during concurrent treatment. There were no grade IV- or treatment-related deaths during this study. Disease-free survival (DFS) was 79.2 months (56.3–102.1 months), and the 3-year survival rates were 52.7 %. Conclusions. This 5-fluorouracil infusional scheme has an excellent tolerability profile and favourable efficacy results (AU)

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Adjuvant treatment with infusional 5-fluorouracil in high risk adenocarcinoma of the stomach or gastroesophageal junction.

PURPOSE: In high risk gastric and gastroesophageal adenocarcinoma, adjuvant radiochemotherapy with 5-fluorouracil bolus became a standard adjuvant treatment, showing significant improvement in overall survival after surgery, although with substantial toxicity. We explored the efficacy and toxicity of a modified 5-fluorouracil continuous infusion scheme. METHODS: We conducted an observational retrospective study in our centre. Gastric/gastroesophageal junction adenocarcinoma patients were treated with a schedule consisting in four infusions of bolus 5-fluorouracil 400 mg/m(2) iv with leucovorin 200 mg/m(2) iv and 1200 mg/m(2) in 46-hour infusion of 5-fluorouracil (D'Gramont scheme), followed by concomitant radiochemotherapy (45 Gy in 25 fractions of 1.8 Gy) with 5-fluorouracil continuously infusion 225 mg/m(2)/day and four additional infusions of chemotherapy one month after complete radiochemotherapy. RESULTS: Between January 2007 and December 2013, 55 patients received a mean of 3.16 bi-weekly adjuvant infusions followed by 4.6 weeks of continuous treatment concurrent with radiotherapy and 3.72 bi-weekly infusions after radiotherapy treatment. During adjuvant treatment, grade III toxicity was mostly haematologic, while gastrointestinal and cutaneous toxicity was predominant during concurrent treatment. There were no grade IV- or treatment-related deaths during this study. Disease-free survival (DFS) was 79.2 months (56.3-102.1 months), and the 3-year survival rates were 52.7 %. CONCLUSIONS: This 5-fluorouracil infusional scheme has an excellent tolerability profile and favourable efficacy results.