Characteristics and outcomes of therapy-related myeloid neoplasms after peptide receptor radionuclide/chemoradionuclide therapy (PRRT/PRCRT) for metastatic neuroendocrine neoplasia: a single-institution series

Purpose Peptide receptor radionuclide/chemoradionuclide therapy (PRRT/PRCRT) is an effective therapy for metastatic neuroendocrine neoplasia (NEN), but therapy-related myeloid neoplasms (t-MN) remain of concern. The study reviewed the clinicopathological features and outcomes of patients who develop...

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Published in:European journal of nuclear medicine and molecular imaging 2019-08, Vol.46 (9), p.1902-1910
Main Authors: Goncalves, Isaac, Burbury, Kate, Michael, Michael, Iravani, Amir, Ravi Kumar, Aravind S., Akhurst, Tim, Tiong, Ing S., Blombery, Piers, Hofman, Michael S., Westerman, David, Hicks, Rodney J., Kong, Grace
Format: Article
Language:English
Subjects:
Acute myeloid leukemia
Biomarkers
Cardiology
Chemotherapy
Diagnosis
Gene sequencing
Genetic analysis
Genetic factors
Hematology
Imaging
Leukemia
Medicine
Medicine & Public Health
Metastases
Metastasis
Mutation
Myelodysplastic syndrome
Myelodysplastic syndromes
Neoplasms
Next-generation sequencing
Nuclear Medicine
Oncology
Oncology – Digestive tract
Original Article
Orthopedics
p53 Protein
Pancreas
Pancreatic cancer
Peptides
Radioisotopes
Radiology
Small intestine
Survival
Thrombocytopenia
Tumors
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Summary:Purpose Peptide receptor radionuclide/chemoradionuclide therapy (PRRT/PRCRT) is an effective therapy for metastatic neuroendocrine neoplasia (NEN), but therapy-related myeloid neoplasms (t-MN) remain of concern. The study reviewed the clinicopathological features and outcomes of patients who developed t-MN. Methods Retrospective analysis of all patients diagnosed with t-MN by 2016 WHO classification, from a cohort of 521 patients who received PRRT/PRCRT over a 12-year period. Molecular next-generation sequencing using an in-house 26-gene panel was performed. Results Twenty-five of 521 (4.8%) patients were diagnosed with t-MN, including six acute myeloid leukaemia (AML) and 19 myelodysplastic syndrome (MDS). The median time from first cycle PRRT/PRCRT to diagnosis of t-MN was 26 months (range 4–91). Twenty-two of 25 (88%) patients had grade 1–2 pancreatic or small bowel NEN with moderate metastatic liver burden. Six patients (24%) had prior chemotherapy. Median number of PRRT cycles = 5 (22/25 (88%) with concomitant radiosensitising chemotherapy). All 25 patients achieved disease stabilisation (68%) or partial response (32%) on RECIST 1.1 at 3 months post-PRRT. At t-MN diagnosis, all patients presented with thrombocytopenia (median nadir 33 × 10 9 /L, range 3–75) and 17 (68%) remained NEN progression-free. Marrow genetic analysis revealed unfavourable karyotype in 16/25 (66%) patients with tumour protein 53 (TP53) mutation in nine (36%). Azacitidine therapy was utilised in ten eligible patients, while four received induction chemotherapy for AML. The median overall survival from first PRRT was 62 months (19–94), but from t-MN diagnosis was only 13 months (1–56), with death due primarily to haematological disease progression. Conclusions The diagnosis of t-MN after PRRT/PRCRT is an infrequent but serious complication with poor overall survival. Most patients present with thrombocytopenia; unfavourable genetic mutations have a poor response to t-MN treatment. Prospective data are needed to explore potential pre-existing genetic factors and predictive biomarkers to minimise the risk of t-MN.
ISSN:1619-7070
1619-7089
DOI:10.1007/s00259-019-04389-2