Long-term tolerability of PRRT in 807 patients with neuroendocrine tumours: the value and limitations of clinical factors

Bodei, Lisa; Kidd, Mark; Paganelli, Giovanni; Grana, Chiara Maria; Drozdov, Ignat; Cremonesi, Marta; Lepensky, Christopher; Kwekkeboom, Dik J.; Baüm, Richard; Krenning, Eric P.; Modlin, Irvin M.

doi:10.1007/s00259-014-2893-5

Cited by 394 publications

(399 citation statements)

References 25 publications

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“…In large trials, grade 3 or 4 hematologic toxicity has been reported in 3%-14% of the patients (26)(27)(28). Long-term myelotoxicity in the form of myelodysplastic syndrome or acute leukemia is a rare and severe adverse event associated with PRRT, occurring in 1%-2% of patients (29).…”

Section: Safetymentioning

confidence: 99%

“…SSAs are partially reabsorbed in the proximal tubule cells; counteracting this reabsorption with the coinfusion of positively charged amino acids during treatment results in a mean dose reduction in the kidneys of 40% (32). Severe renal toxicity has been reported in 0%-9% of patients; high incidences have been reported in some trials with 90 Y because of its biologic and physical properties and treatment in an early era without amino acid renal protection (26,27). With renal protection being the standard of care in international protocols, some radiation nephropathy is still considered normal.…”

Section: Safetymentioning

confidence: 99%

“…However, although renal dosimetry is more reliable, bone marrow dosimetry is still in need of fine-tuning. Because threshold doses for renal toxicity are infrequently reached or are largely exceeded with standard 177 Lu-based PRRT, and because long-term followup of large patient cohorts has indicated a very low risk of severe renal toxicity, routine dosimetry stratification of PRRT candidates is worth exploring in nonstandard treatments, such as retreatments (or salvage treatments) (26,35,36). Given that the bone marrow is …”

Section: Safetymentioning

confidence: 99%

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Somatostatin Receptor 2–Targeting Compounds

Duijzentkunst

Bodei

2017

J Nucl Med

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The molecular imaging and treatment of neuroendocrine tumors (NETs) with radiolabeled somatostatin analogs represent a milestone in the development of theranostic compounds. Whole-body scintigraphy with 111 In-pentetreotide has revolutionized the diagnosis and staging of NETs and the evaluation of treatment outcomes. At present, diagnostic accuracy with positron-emitting radionuclides is greater than 90%. Peptide receptor radionuclide therapy (PRRT) has become a well-accepted treatment for patients with welldifferentiated inoperable or metastatic NETs and disease progression after first-line treatment. Disease control rates (complete or partial remission or stable disease in patients with formerly progressive disease) of up to 95%, with a low incidence of long-term hematologic and renal toxicity, have been reported. In a recently published randomized trial, compared with intensified treatment of midgut NETs with longacting and repeatable octreotide, PRRT reduced the hazard of disease progression and death by 79%. Upcoming developments in PRRT include the use of somatostatin receptor antagonists and a-emitting radionuclides, which may further enhance treatment outcomes.

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Section: Safetymentioning

confidence: 99%

Section: Safetymentioning

confidence: 99%

Section: Safetymentioning

confidence: 99%

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Somatostatin Receptor 2–Targeting Compounds

Duijzentkunst

Bodei

2017

J Nucl Med

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“…A dose in the range of 2.7-5.4 GBq is administered according to standard protocols proposed by European Association of Nuclear Medicine (EANM). In order to protect the renal function, positively charged amino acids are coadministered (lysine and arginine) [8,9]. It is known that this kind of peptide binds very quickly to tumor tissue, while the rest of the activity is excreted through the kidneys and bladder.…”

Section: Methodsmentioning

confidence: 99%

Compartment Biokinetic Model for 90y-Dotatoc

Jeremic¹,

Matović²,

Pantović³

et al. 2017

RAD Conference Proceedings

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Abstract. Biokinetic of 90 Y-DOTATOC in human body during treatment of neuroendocrine and medullary thyroid tumors is described in this work. For this purpose, the human body may be represented by 4 compartments: blood, kidneys, urinary bladder and tumor. System of differential equations was developed, whose solution is presented in this paper. The aim is the determination of transfer coefficients between individual compartments for a better estimation of the dose in the tumor and other organs of the human body. A computer program is written in standard Fortran90 programming language.

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“…The first reports of these complications were in association with high-administered activities of 111 Indiethylenetriaminepentaacetic acid (DTPA)-octreotide delivered therapeutically to cumulative activities in excess of 100 GBq [26] but have also been seen in patients receiving 177 Lu [8] and 90 Y SSAs [9]. In an article recently published in the European Journal of Nuclear Medicine and Molecular Imaging, Bodei et al [27] analyse the toxicity associated with PRRT in 807 patients with NET treated at their facility. This series provides further evidence of the low side effect profile of PRRT.…”

mentioning

confidence: 99%