Publicação
Comparison of two 177Lu-DOTATATE quantification methods for patient personalized dosimetry in therapy of neuroendocrine tumors
| Resumo: | Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE is remarkably effective in the treatment of neuroendocrine tumors (NETs) over-expressing somatostatin receptors. Besides potential renal and/or hematological toxicity, the significant response inter-patient variability requires individual treatment planning. Several methods have been used to quantify tissue absorbed dose. The aim of this study was to compare the dosimetry calculated by two computational methods on a retrospective analysis of 177Lu-DOTATATE PRRT clinical cases. Furthermore, we investigated toxicity and the feasibility of pre-treatment dosimetry with 68Ga-DOTANOC PET/CT scans to estimate the optimal radiation activity to each patient. Twenty-four treatments from six patients with histologically confirmed inoperable and/or metastatic NETs over-expressing somatostatin receptors were analyzed (4 cycles/patient). A mean activity of 7.2 ± 0.5 GBq/cycle of 177Lu-DOTATATE was injected, after which patients underwent acquisition of serial whole-body planar images, and abdominal SPECT and CT scans. After processing, pre- and post-therapeutic scans were used for patient-specific voxel-wise absorbed dose quantification. Dosimetry with pre-calculated voxel S-values (VSVs) was performed with an in-house program. Monte Carlo (MC) dosimetry was performed with TOPAS (Geant4) MC tool. Cumulative dose-volume histograms (cDVHs) were generated and mean absorbed dose was compared using the intraclass correlation coefficient (ICC) and relative difference (RD). MC dosimetry entailed a simulation time of around 2 days/simulation while the VSV method took less than 1 minute/computation, in the same workstation. Good agreement (ICC > 0.80) was found for organ and NETs absorbed dose distribution obtained with both methods, with similar cDVHs. According to both post-treatment SPECT and pre-treatment PET data, the highest median RD of -3.6% (min = - 25.6%, max = 3.8%) and -8.3% (-30.8%, 2.5%) were seen, respectively, for the bone marrow (ICC = 0.999) and spleen (ICC = 0.846). Differences are presumably due to patient morphology considerations in MC simulations. Patient-specific dosimetry revealed that in half of the patients the bone marrow was the absorbed dose limiting organ. Lastly, significant deviations, from -83.1% up to 358.5%, were found between the absorbed dose data estimated with the pre- and post-therapeutic scans, which are possibly related with the different kinetics and binding profile of the two tracers. This study reveals identical patient-specific 3D absorbed dose distributions for both methods, in the abdominal region. Thus, the VSV approach appears to be a suitable option for routine clinical dosimetry in 177Lu-DOTATATE PRRT patients, considering the short computation time and accuracy. Data suggests that half of the patients had a bone marrow absorbed dose superior to the maximum value recommended, which could have been avoided if personalized dosimetry had been performed for each cycle/treatment. However, we cannot conclude about the treatment efficacy if that reduction had been implemented. Unfortunately, results do not support the possibility of treatment planning with a pretherapeutic 68Ga-DOTANOC PET/CT scan. Despite the small patient cohort, we hope that our results contribute to the development of a standard dosimetry protocol for PRRT. |
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| Autores principais: | Rodrigues, Cristiana Magalhães Correia |
| Assunto: | Tumores Neuroendócrinos 177Lu-DOTATATE PRRT Internal Dosimetry Monte Carlo Voxel S-values Teses de mestrado - 2021 |
| Ano: | 2021 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE is remarkably effective in the treatment of neuroendocrine tumors (NETs) over-expressing somatostatin receptors. Besides potential renal and/or hematological toxicity, the significant response inter-patient variability requires individual treatment planning. Several methods have been used to quantify tissue absorbed dose. The aim of this study was to compare the dosimetry calculated by two computational methods on a retrospective analysis of 177Lu-DOTATATE PRRT clinical cases. Furthermore, we investigated toxicity and the feasibility of pre-treatment dosimetry with 68Ga-DOTANOC PET/CT scans to estimate the optimal radiation activity to each patient. Twenty-four treatments from six patients with histologically confirmed inoperable and/or metastatic NETs over-expressing somatostatin receptors were analyzed (4 cycles/patient). A mean activity of 7.2 ± 0.5 GBq/cycle of 177Lu-DOTATATE was injected, after which patients underwent acquisition of serial whole-body planar images, and abdominal SPECT and CT scans. After processing, pre- and post-therapeutic scans were used for patient-specific voxel-wise absorbed dose quantification. Dosimetry with pre-calculated voxel S-values (VSVs) was performed with an in-house program. Monte Carlo (MC) dosimetry was performed with TOPAS (Geant4) MC tool. Cumulative dose-volume histograms (cDVHs) were generated and mean absorbed dose was compared using the intraclass correlation coefficient (ICC) and relative difference (RD). MC dosimetry entailed a simulation time of around 2 days/simulation while the VSV method took less than 1 minute/computation, in the same workstation. Good agreement (ICC > 0.80) was found for organ and NETs absorbed dose distribution obtained with both methods, with similar cDVHs. According to both post-treatment SPECT and pre-treatment PET data, the highest median RD of -3.6% (min = - 25.6%, max = 3.8%) and -8.3% (-30.8%, 2.5%) were seen, respectively, for the bone marrow (ICC = 0.999) and spleen (ICC = 0.846). Differences are presumably due to patient morphology considerations in MC simulations. Patient-specific dosimetry revealed that in half of the patients the bone marrow was the absorbed dose limiting organ. Lastly, significant deviations, from -83.1% up to 358.5%, were found between the absorbed dose data estimated with the pre- and post-therapeutic scans, which are possibly related with the different kinetics and binding profile of the two tracers. This study reveals identical patient-specific 3D absorbed dose distributions for both methods, in the abdominal region. Thus, the VSV approach appears to be a suitable option for routine clinical dosimetry in 177Lu-DOTATATE PRRT patients, considering the short computation time and accuracy. Data suggests that half of the patients had a bone marrow absorbed dose superior to the maximum value recommended, which could have been avoided if personalized dosimetry had been performed for each cycle/treatment. However, we cannot conclude about the treatment efficacy if that reduction had been implemented. Unfortunately, results do not support the possibility of treatment planning with a pretherapeutic 68Ga-DOTANOC PET/CT scan. Despite the small patient cohort, we hope that our results contribute to the development of a standard dosimetry protocol for PRRT. |
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