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

Isaac Goncalves, Kate Burbury, Michael Michael, Amir Iravani, Aravind S. Ravi Kumar, Tim Akhurst, Ing S. Tiong, Piers Blombery, Michael S. Hofman, David Westerman, Rodney J. Hicks, Grace Kong

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Abstract

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 × 109/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.

Original languageEnglish
Pages (from-to)1902-1910
Number of pages9
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume46
Issue number9
DOIs
StatePublished - Aug 1 2019

Keywords

  • Acute myeloid leukaemia
  • Lu-DOTATATE
  • Myelodysplasia
  • Neuroendocrine neoplasm
  • Pepetide receptor radionuclide therapy
  • Therapy-related myeloid neoplasm

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