Salvage PRRT with 177Lu-DOTA-octreotate in extensively pretreated patients with metastatic neuroendocrine tumor (NET): dosimetry, toxicity, efficacy, and survival

Rudisile, Simon; Gosewisch, Astrid; Wenter, Vera; Unterrainer, Marcus; Böning, Guido; Gildehaus, Franz Josef; Fendler, Wolfgang P.; Auernhammer, Christoph J.; Spitzweg, Christine; Bartenstein, Peter; Todica, Andrei; Ilhan, Harun

doi:10.1186/s12885-019-6000-y

Cited by 73 publications

(80 citation statements)

References 27 publications

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“…It has also been demonstrated that absorbed doses delivered to healthy organs and tumours have large interpatient variability [5][6][7][8]. Moreover, many studies have provided evidence of dose-effect correlations in PRRT [9][10][11]. For these reasons groups from different hospitals and research institutes across Europe have proposed the use of dosimetry for PRRT in routine clinical practice [12].…”

Section: Introductionmentioning

confidence: 99%

Uncertainty analysis of tumour absorbed dose calculations in Molecular Radiotherapy

Finocchiaro

Gear

Fioroni³

et al. 2020

Preprint

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Background: Internal dosimetry evaluation consists of a multi-step process ranging from imaging acquisition to absorbed dose calculations. Assessment of uncertainty is complicated and, for that reason, it is commonly ignored in clinical routine. However, it is essential for adequate interpretation of the results. Recently, the EANM published a practical guidance on uncertainty analysis for molecular radiotherapy based on the application of the law of propagation of uncertainty. In this study, we investigated the overall uncertainty on a sample of patient following the EANM guidelines. The aim of this study was to provide an indication of the typical uncertainties that may be expected from performing dosimetry, to determine parameters that have the greatest effect on the accuracy of calculations and to consider the potential improvements that could be made if these effects were reduced.Results: Absorbed doses and the relative uncertainties were calculated for a sample of 49 patients and a total of 154 tumours. A wide range of relative absorbed dose uncertainty values was observed (14 - 102%). Uncertainties associated with each quantity along the absorbed dose calculation chain (i.e. Volume, Recovery Coefficient, Calibration Factor, Activity, Time-Activity Curve Fitting, Time-Integrated Activity and Absorbed Dose) were estimated. An equation was derived to describe relationship between the uncertainty in the absorbed dose and the volume. The largest source of error was the VOI delineation. By postulating different values of FWHM, the impact of the imaging system spatial resolution on the uncertainties was investigated.Discussion: To the best of our knowledge, this is the first analysis of uncertainty in molecular radiotherapy based on a cohort of clinical cases. Wide inter-lesion variability of absorbed dose uncertainty was observed. Hence, a proper assessment of the uncertainties associated with the calculations should be considered as a basic scientific standard. A model for a quick estimate of uncertainty without implementing the entire error propagation schema, which may be useful in clinical practice, was presented. Ameliorating spatial resolution may be in future the key factor for accurate absorbed dose assessment.

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Section: Introductionmentioning

confidence: 99%

Uncertainty analysis of tumour absorbed dose calculations in Molecular Radiotherapy

Finocchiaro

Gear

Fioroni³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…It has also been demonstrated that absorbed doses delivered to healthy organs and tumours have large inter-patient variability [5][6][7][8]. Moreover, many studies have provided evidence of dose-effect correlations in PRRT [9][10][11]. For these reasons, groups from different hospitals and research institutes across Europe have proposed the use of dosimetry for PRRT in routine clinical practice [12].…”

Section: Introductionmentioning

confidence: 99%

Uncertainty analysis of tumour absorbed dose calculations in molecular radiotherapy

et al. 2020

View full text Add to dashboard Cite

Background Internal dosimetry evaluation consists of a multi-step process ranging from imaging acquisition to absorbed dose calculations. Assessment of uncertainty is complicated and, for that reason, it is commonly ignored in clinical routine. However, it is essential for adequate interpretation of the results. Recently, the EANM published a practical guidance on uncertainty analysis for molecular radiotherapy based on the application of the law of propagation of uncertainty. In this study, we investigated the overall uncertainty on a sample of a patient following the EANM guidelines. The aim of this study was to provide an indication of the typical uncertainties that may be expected from performing dosimetry, to determine parameters that have the greatest effect on the accuracy of calculations and to consider the potential improvements that could be made if these effects were reduced. Results Absorbed doses and the relative uncertainties were calculated for a sample of 49 patients and a total of 154 tumours. A wide range of relative absorbed dose uncertainty values was observed (14–102%). Uncertainties associated with each quantity along the absorbed dose calculation chain (i.e. volume, recovery coefficient, calibration factor, activity, time-activity curve fitting, time-integrated activity and absorbed dose) were estimated. An equation was derived to describe the relationship between the uncertainty in the absorbed dose and the volume. The largest source of error was the VOI delineation. By postulating different values of FWHM, the impact of the imaging system spatial resolution on the uncertainties was investigated. Discussion To the best of our knowledge, this is the first analysis of uncertainty in molecular radiotherapy based on a cohort of clinical cases. Wide inter-lesion variability of absorbed dose uncertainty was observed. Hence, a proper assessment of the uncertainties associated with the calculations should be considered as a basic scientific standard. A model for a quick estimate of uncertainty without implementing the entire error propagation schema, which may be useful in clinical practice, was presented. Ameliorating spatial resolution may be in future the key factor for accurate absorbed dose assessment.

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“…In contrast a previous smaller study including 35 mainly GI and BP G2 NET showed the shortest PFS of six months. This is surprising as progression in that study was de ned according to RECIST (response evaluation criteria in solid tumors) which would statistically lead to a longer PFS compared to the studies using clinical progression [37].…”

Section: Discussionmentioning

confidence: 92%

Clinical Efficacy of First and Second Series of Peptide Receptor Radionuclide Therapy in Patients With Neuroendocrine Neoplasm: A Cohort Study

Zacho

Iversen

Villadsen

et al. 2020

Preprint

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Abstract Background Peptide receptor radionuclide therapy (PRRT) is an established treatment for metastatic neuroendocrine neoplasms (NEN) with positive effects on progression free (PFS) and overall survival (OS), but only limited data exists for the effect of multiple series of PRRT. The aim of this study was to investigate PFS and OS in NEN patients treated with multiple series of PRRT conforming to the ENETS treatment protocol. Methods We included all patients with gastrointestinal (GI), pancreatic and bronchopulmonary (BP) NEN treated with PRRT from 2008 to 2018. We used Kaplan-Meier estimation to evaluate PFS and OS with subgroup analysis of primary tumor, Ki67-index, type of radioisotope and number of PRRT series. Results Of 150 patients, 133 patients were included with female/male 61/72, median age 70 (interquartile range 64–76) years. GI-NEN comprised 62%, pancreatic 23% and BP 11%. Median Ki67-index was 5%. After first PRRT G1- and G2-tumors had PFS of 25 and 22 months, compared to 11 months in G3-NENs (p < 0.05) and PFS was longer in G1/G2 GI-NENs than BP-NEN (30 vs. 12 months, p < 0.05). After retreatment with a second series of PRRT, the overall PFS (G1-G3) was 19 months, with G1- and G2-tumors having the highest PFS of 19 and 22 months, respectively. Overall, the GI and BP tumors had an OS of 54 and 51 months. Conclusions PRRT is an effective therapy with long-term PFS and OS, especially in G1 and G2 NENs, and with better prognosis in GI-NEN compared with BP-NENs. OS and PFS was shorter after the second series of PRRT compared with the first, however results were still encouraging.

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Salvage PRRT with 177Lu-DOTA-octreotate in extensively pretreated patients with metastatic neuroendocrine tumor (NET): dosimetry, toxicity, efficacy, and survival

Cited by 73 publications

References 27 publications

Uncertainty analysis of tumour absorbed dose calculations in Molecular Radiotherapy

Uncertainty analysis of tumour absorbed dose calculations in Molecular Radiotherapy

Uncertainty analysis of tumour absorbed dose calculations in molecular radiotherapy

Clinical Efficacy of First and Second Series of Peptide Receptor Radionuclide Therapy in Patients With Neuroendocrine Neoplasm: A Cohort Study

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