Myeloid neoplasms after chemotherapy and PRRT: myth and reality

Bodei, Lisa; Modlin, Irvin M.; Luster, Markus; Forrer, Flavio; Cremonesi, Marta; Hicks, Rodney J.; Ezziddin, Samer; Kidd, Mark; Chiti, Arturo

doi:10.1530/erc-16-0258

Cited by 37 publications

(25 citation statements)

References 48 publications

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“…The spectrum of permanent myelotoxicity ranges from reduction of bone marrow reserve to secondary myeloproliferative diseases (myelodysplastic syndrome and leukaemia) but these are rare (approximately 2%). They do not occur more frequently than with other myelotoxic treatments [232][233][234].…”

Section: Peptide Receptor Radionuclide Therapymentioning

confidence: 86%

“…Acute side effects include mild nausea (25% of patients) and vomiting related to the co-administered nephro-protective amino acid infusion (in up to 10%) [231]. Subacute effects include mild to moderate fatigue, mild alopecia and mild hematologic toxicity (WHO grades 1 or 2) transiently in 85-90% of patients [232]. Severe (grades 3 and 4) toxicity occurs in 10-15% irrespective of the type of radiopeptide used; this is usually reversible and very rarely requires transfusion or granulocyte support [231].…”

Section: Peptide Receptor Radionuclide Therapymentioning

confidence: 99%

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Neuroendocrine Neoplasms of the Small Bowel and Pancreas

et al. 2019

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The traditionally promulgated perspectives of neuroendocrine neoplasms (NEN) as rare, indolent tumours are blunt and have been outdated for the last 2 decades. Clear increments in their incidence over the past decades render them increasingly clinically relevant, and at initial diagnosis many present with nodal and/or distant metastases (notably hepatic). The molecular pathogenesis of these tumours is increasingly yet incompletely understood. Those arising from the small bowel (SB) or pancreas typically occur sporadically; the latter may occur within the context of hereditary tumour predisposition syndromes. NENs can also be associated with endocrinopathy of hormonal hypersecretion. Tangible advances in the development of novel biomarkers, functional imaging modalities and therapy are especially applicable to this sub-set of tumours. The management of SB and pancreatic neuroendocrine tumours (NET) may be challenging, and often comprises a multidisciplinary approach wherein surgical, medical, interventional radiological and radiotherapeu-tic modalities are implemented. This review provides a comprehensive overview of the epidemiology, pathophysiology, diagnosis and treatment of SB and pancreatic NETs. Moreover, we provide an outlook of the future in these tumour types which will include the development of precision oncology frameworks for individualised therapy, multi-analyte predictive biomarkers, artificial intelligence-derived clinical decision support tools and elucidation of the role of the microbiome in NEN development and clinical behaviour.According to SEER version 18, SBNEN and PanNEN incidences are currently estimated at 1.2 and 0.7 per 100,000, respectively [5]. The overall 20-year duration prevalence of all NEN is estimated at 171,321; SBNEN constituting 32,122 patients with 3-fold fewer PanNEN (10,707) [5]. Possible attributable factors for this increase evolving epidemiology include increased use of endoscopy and also improvements in the sensitivity of widely used imaging modalities, leading to increased detection of early-stage, asymptomatic disease [5].The median overall survival (OS) for NEN (irrespective of site and grade) is 9.3 years [5]. For SB (median OS: 14 years), this ranges from 70 months (advanced disease with distant metastases) to 170 months (localised disease) and from 30 months (Grade 3) to 160 months (Grade 1). For pancreas (median OS: 3.6 years): 21 months (advanced) to 235 months (localised disease) and from 15 months (Grade 3) to 140 months (Grade 1) [5].Multivariable analyses have identified that ethnicity, age, differentiation, stage and site all have statistically significant correlations with survival. In general, Caucasian ethnicity, age (< 50 years) and localised, well-differentiated NEN exhibit the best survival. SB tumour patients are approximately 1.5 times more likely to survive longer than those with PanNEN [19]. Many of these correlations are self-evident since they pertain to degree of malignancy, disease duration and patient performance status.OS (median 5-year) app...

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Section: Peptide Receptor Radionuclide Therapymentioning

confidence: 86%

Section: Peptide Receptor Radionuclide Therapymentioning

confidence: 99%

Neuroendocrine Neoplasms of the Small Bowel and Pancreas

et al. 2019

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“…In lower-grade NETs, which would be expected to have longer survival independent of therapeutic effects, the potential benefits of chemotherapy need to be balanced against the risks of inducing MDS or leukaemia, which may be more likely when an alkylating agent like temozolomide is used [53]. 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].…”

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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“…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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Myeloid neoplasms after chemotherapy and PRRT: myth and reality

Cited by 37 publications

References 48 publications

Neuroendocrine Neoplasms of the Small Bowel and Pancreas

Neuroendocrine Neoplasms of the Small Bowel and Pancreas

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

Somatostatin Receptor 2–Targeting Compounds

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