Myelotoxicity of Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: A Decade of Experience

Kesavan, M.R.; Turner, J. Harvey

doi:10.1089/cbr.2016.2035

Cited by 56 publications

(56 citation statements)

References 37 publications

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“…A recent report from France, where alkylating agents are widely used in chemotherapy regimens, indicated that 20% of patients receiving PRRT as a salvage therapy developed MDS [54] but these data have been disputed by a more comprehensive review of the experience with PRRT from multiple international trials and reported case series [55]. The overall risks of MDS and leukaemia appear to be low (<2%) with PRRT, as described in a recent comprehensive review of the literature [56]. Accordingly, a small increase in the risk of MDS by combining PRRT with an alkylating agent like temozolomide could be best justified in patients with a poor prognosis and a high likelihood of disease progression.…”

Section: Netter-1: the First Randomized Controlled Trial Of Prrtmentioning

confidence: 99%

ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Peptide Receptor Radionuclide Therapy with Radiolabelled Somatostatin Analogues

et al. 2017

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The purpose of these guidelines is to assist physicians caring for patients with neuroendocrine neoplasia in considering eligibility criteria for peptide receptor radionuclide therapy (PRRT) and in defining the minimum requirements for PRRT. It is not these guidelines' aim to give recommendations on the use of specific radiolabelled somatostatin analogues for PRRT as different analogues are being used, and their availability is governed by varying international regulations. However, a recent randomized controlled trial, NETTER-1, has provided evidence that may establish ¹⁷⁷Lu-DOTA-octreotate (LutaThera®) as the first widely approved agent. It also makes recommendations on what minimal patient, tumour, and treatment outcome characteristics should be reported for PRRT to facilitate robust comparisons between studies.

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Section: Netter-1: the First Randomized Controlled Trial Of Prrtmentioning

confidence: 99%

ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Peptide Receptor Radionuclide Therapy with Radiolabelled Somatostatin Analogues

et al. 2017

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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). Incidence rates are higher in patients who have been heavily pretreated with alkalizing chemotherapeutics, probably reflecting the myelotoxic properties of these agents (30,31).…”

Section: Safetymentioning

confidence: 99%

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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“…At the same time the grade 3/4 hematotoxicity was observed in 10.2% (7/68) of NET patients treated with 177 Lu (Sabet et al 2013b) having bone metastases and no hematotoxicity apart from grade 1 anemia in one out of six NET patients treated with 177 Lu (Basu et al 2016) having extensive bone marrow involvement shows that PRRT is well tolerated in this group of patients. Furthermore, MDS or AL were reported to range from 1.4% (3/208) with 177 Lu (Sabet et al 2013a); 2.0% (22/148) with 90 Y or 177 Lu (Baum et al 2018); 2.2% (13/582) with 177 Lu (Brabander et al 2017); and to 1.4% (32/2225) in the meta-analysis comprising 16 studies (Kesavan & Turner 2016). The identified risk factors for hematotoxicity were impaired renal function, low white blood cell count, extensive tumor mass, high tumor uptake on the scans and/or advanced age, cumulative administered activity (>29.6 GBq) and initial cytopenias, prior number of therapies, prior chemotherapy (alkylating agents), and prior radiotherapy (Sabet et al 2013a, Bergsma et al 2016b, Kesavan & Turner 2016.…”

Section: Toxicity Profiles Of Prrtmentioning

confidence: 99%

“…The main predictors of poor OS outcome after PRRT are non-specific and include high Ki-67 index (greater than 10%), high uptake on 18 F-FDG, involvement of more than two organ systems, local vs distant metastases, low Karnofsky performance score (≤70%), high tumor burden, identified progressive disease after first PRRT, and when PRRT is delivered as salvage therapy after chemotherapy (Delpassand et al 2014, Bodei et al 2015b, Kesavan & Turner 2016, Gabriel et al 2019, Wolf et al 2019. In another study, highly elevated maximum standardized uptake values (SUV max ) on pre-therapeutic 68 Ga-DOTATOC were associated with tumor shrinkage, reduction of tumor markers, and improved overall clinical…”

Section: Prognostic Markers For Prrt In Netmentioning

confidence: 99%

Molecular imaging and radionuclide therapy of pheochromocytoma and paraganglioma in the era of genomic characterization of disease subgroups

Taïeb

Jha

Treglia

2019

Endocrine-Related Cancer

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In recent years, advancement in genetics has profoundly helped to gain a more comprehensive molecular, pathogenic, and prognostic picture of pheochromocytomas and paragangliomas (PPGLs). Newly discovered molecular targets, particularly those that target cell membranes or signaling pathways have helped move nuclear medicine in the forefront of PPGL precision medicine. This is mainly based on the introduction and increasing experience of various PET radiopharmaceuticals across PPGL genotypes quickly followed by implementation of novel radiotherapies and revised imaging algorithms. Particularly, 68Ga-labeled-SSAs have shown excellent results in the diagnosis and staging of PPGLs and in selecting patients for PRRT as a potential alternative to 123/131I-MIBG theranostics. PRRT using 90Y/177Lu-DOTA-SSAs has shown promise for treatment of PPGLs with improvement of clinical symptoms and/or disease control. However, more well-designed prospective studies are required to confirm these findings, in order to fully exploit PRRT’s antitumoral properties to obtain the final FDA approval. Such an approval has recently been obtained for high‐specific-activity 131I-MIBG for inoperable/metastatic PPGL. The increasing experience and encouraging preliminary results of these radiotherapeutic approaches in PPGLs now raises an important question of how to further integrate them into PPGL management (e.g. monotherapy or in combination with other systemic therapies), carefully taking into account the PPGLs locations, genotypes, and growth rate. Thus, targeted radionuclide therapy (TRT) should preferably be performed at specialized centers with an experienced interdisciplinary team. Future perspectives include the introduction of dosimetry and biomarkers for therapeutic responses for more individualized treatment plans, α-emitting isotopes, and the combination of TRT with other systemic therapies.

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Myelotoxicity of Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: A Decade of Experience

Abstract: Early therapy with PRRT-containing regimens improves outcomes, minimizes myelotoxicity, and renders the risk of MDS and AL negligible.

Cited by 56 publications

References 37 publications

ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Peptide Receptor Radionuclide Therapy with Radiolabelled Somatostatin Analogues

ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Peptide Receptor Radionuclide Therapy with Radiolabelled Somatostatin Analogues

Somatostatin Receptor 2–Targeting Compounds

Molecular imaging and radionuclide therapy of pheochromocytoma and paraganglioma in the era of genomic characterization of disease subgroups

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