Nefrotoxicidad y hematotoxicidad un año después de cuatro ciclos de terapia con péptidos marcados con radionúclidos (PRRT) y su impacto en la planificación del tratamiento futuro. Un análisis retrospectivo / Nephrotoxicity and hematotoxicity one year after four cycles of peptide receptor radionuclide therapy (PRRT) and its impact on future treatment planning. A retrospective analysis

Introducción: La nefrotoxicidad y la hematotoxicidad después de la terapia con péptidos marcados con radionúclidos (PRRT) se han descrito en múltiples estudios usando diferentes actividades acumulativas, número de ciclos o péptidos marcados con radionúclidos. Aunque los tumores neuroendocrinos (NET) altamente diferenciados con metástasis tienen una larga supervivencia libre de progresión, pueden progresar. Analizamos los efectos secundarios a largo plazo en un esquema de tratamiento homogéneo en pacientes con PRRT y su impacto en el futuro tratamiento oncológico en caso de progresión. Métodos: De nuestra base de datos se analizaron 89 de 384 pacientes que recibieron la misma PRRT (Lu-177-DOTATATE o Y-90-DOTATOC) cuatro veces cada 10 a 12 semanas y un seguimiento a los 12 meses. Un paciente recibió tres y 11 pacientes recibieron dos veces cuatro ciclos de PRRT, lo que dio lugar a 102 casos. Se compararon el índice de filtrado glomerular estimado (FGe), la Hb, los glóbulos blancos y las plaquetas antes del primer ciclo de terapia y un año después del cuarto ciclo. La clasificación del FGe se realizó según la clasificación de la enfermedad renal crónica (ERC) y la clasificación de la hematotoxicidad según los Criterios Terminológicos Comunes para Eventos Adversos (CTCAE). También se evaluó el impacto de la edad, el sexo, la actividad acumulada y el tipo de PRRT en la toxicidad a largo plazo. Resultados: El grado 1-2 del FGe se redujo de 87/102 al inicio a 71 casos en el seguimiento (p < 0,001). Antes del tratamiento se encontró grado 3a en 13, grado 3b en 2, y en el seguimiento grado 3a en 25, grado 3b en cinco casos, y grado 4 en 1 caso. La anemia antes de la PRRT y en el seguimiento fue de grado 0 en 63 vs. 48 (p < 0,001), de grado 1 en 36 vs. 48, y de grado 2 en tres vs. seis casos. En el recuento de glóbulos blancos y plaquetas no se produjeron cambios significativos en la clasificación (AU)

Introduction: Nephro- and hematotoxicity after peptide receptor radionuclide therapy (PRRT) have been described in multiple studies with heterogeneous cumulative activities, number of cycles or radiolabelled peptides. Though highly differentiated metastasized neuroendocrine tumours (NET) have long progression free survival, they may progress. We analysed long-term side effects in a homogenous treatment schedule in PRRT-patients and their impact on future oncologic treatment in case of progression. Methods: From our database 89/384 patients receiving the same PRRT (Lu-177-DOTATATE or Y-90-DOTATOC) 4 times every 10 to 12 weeks and a follow-up at 12 months were analysed. One patient had three and 11 patients had two times four PRRT-cycles resulting in 102 cases. eGFR, Hb, WBC and platelets before the first and one year after the fourth therapy cycle were compared. eGFR-Grading was done according to chronic kidney disease classification (CKD) and grading of hematotoxicity according to Common Terminology Criteria for Adverse Events (CTCAE). Impact of age, gender, cumulative activity, type of PRRT on long-term-toxicity was also assessed. Results: eGFR grade 1-2 dropped from 87/102 at the baseline to 71 cases at follow-up (p<0.001). Before treatment grade 3a was found in 13, grade 3b in 2 cases, and at follow-up grade 3a in 25, grade 3b in 5, and grade 4 in 1 case. Anaemia prior to PRRT and at follow-up was grade 0 in 63 versus 48 (p<0.001), grade 1 in 36 versus 48, and grade 2 in three versus six cases. In white blood cell count and platelets, there were no significant changes in grading occurring. Subgroup analysis revealed that only in the age group 65 and older was there a higher incidence for anaemia (p=0.006) (AU)

Nephrotoxicity and hematotoxicity one year after four cycles of peptide receptor radionuclide therapy (PRRT) and its impact on future treatment planning. A retrospective analysis. / Nefrotoxicidad y hematotoxicidad un año después de cuatro ciclos de terapia con péptidos marcados con radionúclidos (PRRT) y su impacto en la planificación del tratamiento futuro. Un análisis retrospectivo.

INTRODUCTION: Nephro- and hematotoxicity after peptide receptor radionuclide therapy (PRRT) have been described in multiple studies with heterogeneous cumulative activities, number of cycles or radiolabelled peptides. Though highly differentiated metastasized neuroendocrine tumours (NET) have long progression free survival, they may progress. We analysed long-term side effects in a homogenous treatment schedule in PRRT-patients and their impact on future oncologic treatment in case of progression. METHODS: From our database 89/384 patients receiving the same PRRT (Lu-177-DOTATATE or Y-90-DOTATOC) 4 times every 10 to 12 weeks and a follow-up at 12 months were analysed. One patient had three and 11 patients had two times four PRRT-cycles resulting in 102 cases. eGFR, Hb, WBC and platelets before the first and one year after the fourth therapy cycle were compared. eGFR-Grading was done according to chronic kidney disease classification (CKD) and grading of hematotoxicity according to Common Terminology Criteria for Adverse Events (CTCAE). Impact of age, gender, cumulative activity, type of PRRT on long-term-toxicity was also assessed. RESULTS: eGFR grade 1-2 dropped from 87/102 at the baseline to 71 cases at follow-up (p<0.001). Before treatment grade 3a was found in 13, grade 3b in 2 cases, and at follow-up grade 3a in 25, grade 3b in 5, and grade 4 in 1 case. Anaemia prior to PRRT and at follow-up was grade 0 in 63 versus 48 (p<0.001), grade 1 in 36 versus 48, and grade 2 in three versus six cases. In white blood cell count and platelets, there were no significant changes in grading occurring. Subgroup analysis revealed that only in the age group 65 and older was there a higher incidence for anaemia (p=0.006). CONCLUSIóN: In roughly 20% of cases an increase in grading of nephro- or hematotoxicity is observed. In those patients, except in one, toxicity findings were mild or moderate one year after completion of four cycles of PRRT with either Y-90- or Lu-177-SST-analogues. In terms of safety, PRRT has no critical impact on further oncologic treatment options in the case of disease progression.

68Ga-DOTATOC PET/CT in the localization of metastatic extra-adrenal paraganglioma and pheochromocytoma compared with 18F-DOPA PET/CT. / Comparación entre la PET/TC con 18F-DOPA y la PET/TC con 68Ga-DOTATOC para la localización del paraganglioma maligno extra-adrenal y el feocromocitoma.

OBJECTIVE: 18F-Fluoro-L-dihydroxyphenylalanine (18F-DOPA) PET offers high sensitivity and specificity in the imaging of non-malignant extra-adrenal paraganglioma (PGL) and pheochromocytoma (PHEO) but lower sensitivity in metastatic disease. These tumours are of neuroendocrine origin and can be detected by 68Ga-DOTA-Tyr3-octreotide (68Ga-DOTA-TOC) PET. Therefore, we compared 68Ga-DOTA-TOC and 18F-DOPA as radiolabels for PET/CT imaging for the diagnosis of metastatic extra-adrenal PGL and PHEO. Combined cross-sectional imaging was the reference standard. METHODS: A total of 6 men and 4 women (age range 22-72 years) with anatomical and/or histologically proven metastatic PGL and PHEO were included in this study. Of these patients, 2 male patients suffered from PHEO, while the remaining 8 patients were diagnosed as metastatic extra-adrenal PGL disease. Comparative evaluation included morphological imaging with CT and functional imaging with 68Ga-DOTA-TOC and 18F-DOPA PET. The imaging results were analyzed on a per-lesion basis. The maximum standardized uptake value (SUVmax) of each functional imaging modality in concordant tumour lesions was measured. RESULTS: Compared with anatomical imaging, the per-lesion detection rate of 68Ga-DOTA-TOC was 100% (McNemar, P<0.01), and that of 18F-DOPA PET was 82.3% (McNemar, P<0.8) in metastatic extra-adrenal PGL and PHEO. Overall, 68Ga-DOTA-TOC PET identified 67 lesions; anatomical imaging identified 62 lesions, and 18F-DOPA PET identified 56 lesions. The SUVmax (mean±SD) of all concordant lesions was 29.3±19.9 for 68Ga-DOTA-TOC PET and 12.3±9.1 for 18F-DOPA PET (Mann-Whitney U test, P<0.0001). CONCLUSION: 68Ga-DOTA-TOC PET offers the highest detection rate in metastatic extra-adrenal PGL and PHEO compared to 18F-DOPA PET and even to diagnostic CT, particularly in bone lesions. Combined functional/anatomical imaging (68Ga-DOTA-TOC PET/CT) enables exact tumour extension to be detected in these rare tumour entities, especially in the case of unclear anatomical correlation.

A rare case of a 123I-MIBG SPECT/CT positive, but 68Ga-DOTA-TOC PET/CT negative pheochromocytoma of the bladder. / Caso infrecuente de feocromocitoma vesical positivo en la SPECT/TC con 123I-MIBG, pero negativo en la PET/TC con 68Ga-DOTA-TOC.

Pheochromocytoma (PHEO) is rare and belongs to the group of neuroendocrine tumours (NETs). These tumours can be found anywhere from the neck to the pelvis associated with sympathetic ganglia. Morphological imaging, for example CT, provides excellent anatomical detail and high sensitivity but lacks specificity as difficulties may occur when distinguishing between tumours derived from the sympathetic nervous system and other tumour entities. In contrast to anatomical imaging, functional imaging (123I-MIBG, 68Ga-DOTA-TOC PET) provides high sensitivity and specificity in detecting NETs. Early detection of PHEO is crucial and has a major effect on treatment and prognosis. This case report describes the important role of anatomical and functional imaging in a patient with a neuroendocrine tumour of unusual origin.