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Introduction: Primary cardiac paragangliomas are rare tumors. Metastatic disease is even rarer. Surgical management is technically challenging, and sometimes even impossible. Available therapeutic modalities for metastatic disease include external beam radiation therapy as well as systemic treatments, namely 131I-MIBG and more recently, peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE. To our knowledge, this is the first case of progressive unresectable cardiac paraganglioma with intracardiac extension treated with dosimetry based personalized PRRT to be reported. This case is of particular interest since it documents for the first time the efficacy, and especially the safety of the 177Lu-DOTATATE PRRT in this precarious context for which therapeutic options are limited. Case Presentation: A 47-year-old man with no medical history consulted for rapidly decreasing exercise tolerance. The investigation demonstrated an unresectable progressing metastatic cardiac paraganglioma with intracardiac extension. The patient was treated with personalized 177Lu-DOTATATE PRRT and showed complete symptomatic and partial anatomical responses, with a progression-free survival of 13 months. Conclusions: PRRT with 177Lu-DOTATATE should be considered for inoperable cardiac paraganglioma. No major hemodynamic complications were experienced. Therapy resulted in safety and substantially improved quality of life. [ABSTRACT FROM AUTHOR]

Purpose: Peptide receptor radionuclide therapy (PRRT) is mostly administered using a fixed injected activity (IA) per cycle. This empiric regime results in highly variable absorbed doses to the critical organs and undertreatment of the majority of patients. We conceived a personalized PRRT protocol in which the IA is adjusted to deliver a prescribed absorbed dose to the kidney, with the aim to safely increase tumour irradiation. We herein report on the initial results of our prospective study of personalized PRRT, the P-PRRT Trial (NCT02754297).Methods: PRRT-naïve patients with progressive and/or symptomatic neuroendocrine tumour (NET) were scheduled to receive a four-cycle induction course of 177Lu-octreotate with quantitative SPECT/CT-based dosimetry. The IA was personalized according to the glomerular filtration rate and the body surface area for the first cycle, and according to the prior renal Gy/GBq for the subsequent cycles. The prescribed renal absorbed dose of 23 Gy was reduced by 25-50% in case of significant renal or haematological impairment. Responders were allowed to receive consolidation or maintenance cycles, for each of which 6 Gy to the kidney were prescribed. We simulated the empiric PRRT regime by fixing the IA at 7.4 GBq per cycle, with the same percentage reductions as above. Radiological, molecular imaging, biochemical, and quality of life responses, as well as safety, were assessed.Results: Fifty-two patients underwent 171 cycles. In 34 patients who completed the induction course, a median cumulative IA of 36.1 (range, 6.3-78.6) GBq was administered, and the median cumulative kidney and maximum tumour absorbed doses were 22.1 (range, 8.3-24.3) Gy and 185.7 (range: 15.2-443.1) Gy respectively. Compared with the simulated fixed-IA induction regime, there was a median 1.26-fold increase (range, 0.47-2.12 fold) in the cumulative maximum tumour absorbed dose, which was higher in 85.3% of patients. In 39 assessable patients, the best objective response was partial response in nine (23.1%), minor response in 14 (35.9%), stable disease in 13 (33.3%) and progressive disease in three patients (7.7%). In particular, 11 of 13 patients (84.6%) with pancreatic NET had partial or minor response. The global health status/quality of life score significantly increased in 50% of patients. Acute and subacute side-effects were all of grade 1 or 2, and the most common were nausea (in 32.7% of patients) and fatigue (in 30.8% of patients) respectively. Subacute grade 3 or 4 toxicities occurred in less than 10% of patients, with the exception of lymphocytopenia in 51.9% of patients, without any clinical consequences however. No patient experienced severe renal toxicity.Conclusions: Personalized PRRT makes it possible to safely increase tumour irradiation in the majority of patients. Our first results indicate a favourable tolerance profile, which appears similar to that of the empiric regime. The response rates are promising, in particular in patients with NET of pancreatic origin. [ABSTRACT FROM AUTHOR]

Purpose: Peptide receptor radionuclide therapy (PRRT) with Lu-octreotate is commonly administered at empiric, fixed amounts of injected radioactivity (IA). This results in highly variable absorbed doses to critical organs and suboptimal treatment of most patients. The primary aims of this study were to design a personalized PRRT (P-PRRT) protocol based on dosimetry, and to perform a simulation of this protocol in a retrospective cohort of patients with neuroendocrine tumours, in order to assess the potential of P-PRRT to safely increase the absorbed dose to the tumour during a four-cycle induction course. Methods: Thirty-six patients underwent 122 fixed-IA Lu-octreotate PRRT cycles with quantitative SPECT/CT-based dosimetry. Twenty-two patients completed a four-cycle induction course (29.6 ± 2.4 GBq cumulative IA), with kidney, bone marrow and maximum tumour absorbed doses of 16.2 ± 5.5, 1.3 ± 0.8, and 114 ± 66 Gy, respectively. We simulated a P-PRRT regime in which the renal absorbed dose per IA was predicted by the body surface area and glomerular filtration rate for the first cycle, and by renal dosimetry of the previous cycle(s) for the following cycles. Personalized IA was adjusted at each cycle in order to reach the prescribed renal absorbed dose of 23 Gy over four cycles (with a 25-50% reduction when renal or bone marrow function was impaired). Simulated IA and absorbed doses were based on actual patient characteristics, laboratory values and absorbed doses per IA delivered at each cycle. Results: In the P-PRRT regime, cumulative IA could have been increased to 43.7 ± 16.5 GBq over four induction cycles (10.9 ± 5.0 GBq per cycle), yielding cumulative kidney, bone marrow and maximum tumour absorbed doses of 21.5 ± 2.5, 1.63 ± 0.61, and 163.4 ± 85.9 Gy, respectively. This resulted in an average 1.48-fold increase in cumulative maximum tumour absorbed dose over empiric PRRT (range, 0.68-2.64-fold; P = 0.0013). Conclusion: By standardizing the renal absorbed dose delivered during the induction course, P-PRRT has the potential to significantly increase tumour absorbed dose, thus to augment the therapeutic benefit while limiting toxicity. [ABSTRACT FROM AUTHOR]

Background: Routine dosimetry is essential for personalized 177Lu-octreotate peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NETs), but practical and robust dosimetry methods are needed for wide clinical adoption. The aim of this study was to assess the accuracy and inter-observer reproducibility of simplified dosimetry protocols based on quantitative single-photon emission computed tomography (QSPECT) with a limited number of scanning time points. We also updated our personalized injected activity (IA) prescription scheme.Methods: Seventy-nine NET patients receiving 177Lu-octreotate therapy (with a total of 279 therapy cycles) were included in our study. Three-time-point (3TP; days 0, 1, and 3) QSPECT scanning was performed following each therapy administration. Dosimetry was obtained using small volumes of interest activity concentration sampling for the kidney, the bone marrow and the tumor having the most intense uptake. Accuracy of the simplified dosimetry based on two-time-point (2TP; days 1 and 3, monoexponential fit) or a single-time-point (1TPD3; day 3) scanning was assessed, as well as that of hybrid methods based on 2TP for the first cycle and 1TP (day 1 or 3; 2TP/1TPD1 and 2TP/1TPD3, respectively) or no imaging at all (based on IA only; 2TP/no imaging (NI)) for the subsequent induction cycles. The inter-observer agreement was evaluated for the 3TP, 2TP, and hybrid 2TP/1TPD3 methods using a subset of 60 induction cycles (15 patients). The estimated glomerular filtration rate (eGFR), body size descriptors (weight, body surface area (BSA), lean body weight (LBW)), and products of both were assessed for their ability to predict IA per renal absorbed dose at the first cycle.Results: The 2TP dosimetry estimates correlated highly with those from the 3TP data for all tissues (Spearman r > 0.99, P < 0.0001) with small relative errors between the methods, particularly for the kidney and the tumor, with median relative errors not exceeding 2% and interdecile ranges spanning over less than 6% and 4%, respectively, for the per-cycle and cumulative estimates. For the bone marrow, the errors were slightly greater (median errors < 6%, interdecile ranges < 14%). Overall, the strength of correlations of the absorbed dose estimates from the simplified methods with those from the 3TP scans tended to progressively decrease, and the relative errors to increase, in the following order: 2TP, 2TP/1TPD3, 1TPD3, 2TP/1TPD1, and 2TP/NI. For the tumor, the 2TP/NI scenario was highly inaccurate due to the interference of the therapeutic response. There was an excellent inter-observer agreement between the three observers, in particular for the renal absorbed dose estimated using the 3TP and 2TP methods, with mean errors lesser than 1% and standard deviations of 5% or lower. The eGFR · LBW and eGFR · BSA products best predicted the ratio of IA to the renal dose (GBq/Gy) for the first cycle (Spearman r = 0.41 and 0.39, respectively; P < 0.001). For the first cycle, the personalized IA proportional to eGFR · LBW or eGFR · BSA decreased the range of delivered renal absorbed dose between patients as compared with the fixed IA. For the subsequent cycles, the optimal personalized IA could be determined based on the prior cycle renal GBq/Gy with an error of less than 21% in 90% of patients.Conclusions: A simplified dosimetry protocol based on two-time-point QSPECT scanning on days 1 and 3 post-PRRT provides reproducible and more accurate dose estimates than the techniques relying on a single time point for non-initial or all cycles and results in limited patient inconvenience as compared to protocols involving scanning at later time points. Renal absorbed dose over the 4-cycle induction PRRT course can be standardized by personalizing IA based on the product of eGFR with LBW or BSA for the first cycle and on prior renal dosimetry for the subsequent cycles. [ABSTRACT FROM AUTHOR]

Introduction: In this study, we compared 18F-FDG-postron emission tomography/computed tomography (PET/CT) and bone scintigraphy accuracies for the detection of bone metastases for primary staging in high-grade prostate cancer (PCa) patients to determine if 18F-FDG-PET/CT could be used alone as a staging modality. Methods: Men with localized high-grade PCa (n=256, Gleason 8-10, International Society of Urological Pathology [ISUP] grades 4 or 5) were imaged with bone scintigraphy and 18F-FDGPET/CT. We compared on a per-patient basis the accuracy of the two imaging modalities, taking intermodality agreement as the standard of truth (SOT). Results: 18F-FDG-PET/CT detected at least one bone metastasis in 33 patients compared to only 26 with bone scan. Of the seven false-negative bone scintigraphies, four (57.1%) were solitary metastases (monometastatic), three (42.9%) were oligometastatic (2-4 lesions), and none were plurimetastatic (>4 lesions). Compared to SOT, 18F-FDG-PET/CT showed higher sensitivity and accuracy than bone scintigraphy (100% vs. 78.8%, and 98.7% vs. 98.2%) for the detection of skeletal lesions. Conclusions: 18F-FDG-PET/CT appears similar or better than conventional bone scans to assess for bone metastases in patients newly diagnosed with high-grade PCa. Since intraprostatic FDGuptake is also a biomarker of failure to radical prostatectomy and that FDG-PET/CT has been shown to be accurate in detecting PCa lymph node metastasis, FDG-PET/CT has the potential to be used as the sole preoperative staging modality in high-grade PCa. [ABSTRACT FROM AUTHOR]

Introduction: In this study, we compared 18 F-fluorodeoxyglucose ( 18 F-FDG)-positron emission tomography/computed tomography (PET/CT) and bone scintigraphy accuracies for the detection of bone metastases for primary staging in high-grade prostate cancer (PCa) patients to determine if 18 F-FDG-PET/CT could be used alone as a staging modality., Methods: Men with localized high-grade PCa (n=256, Gleason 8-10, International Society of Urological Pathology [ISUP] grades 4 or 5) were imaged with bone scintigraphy and 18 F-FDG-PET/CT. We compared, on a per-patient basis, the accuracy of the two imaging modalities, taking inter-modality agreement as the standard of truth (SOT)., Results: 18 F-FDG-PET/CT detected at least one bone metastasis in 33 patients compared to only 26 with bone scan. Of the seven false-negative bone scintigraphies, four (57.1%) were solitary metastases (monometastatic), three (42.9%) were oligometastatic (2-4 lesions), and none were plurimetastatic (>4 lesions). Compared to SOT, 18 F-FDG-PET/CT showed higher sensitivity and accuracy than bone scintigraphy (100% vs. 78.8%, and 98.7% vs. 98.2%) for the detection of skeletal lesions., Conclusions: 18 F-FDG-PET/CT appears similar or better than conventional bone scans to assess for bone metastases in patients newly diagnosed with high-grade PCa. Since intraprostatic FDG uptake is also a biomarker for failure of radical prostatectomy and that FDG-PET/CT has been shown to be accurate in detecting PCa lymph node metastasis, FDG-PET/CT has the potential to be used as the sole preoperative staging modality in high-grade PCa.