scholarly journals Development of hematologic toxicity with sequential treatment of Y90 followed by PRRT in five patients at single institution with metastatic neuroendocrine patients.

2019 ◽  
Vol 5 (suppl) ◽  
pp. 81-81
Author(s):  
Jaswinder Singh ◽  
GINA J Singh
Keyword(s):  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Peptide Receptor Radionuclide Therapy ◽  
Somatostatin Analogues ◽  
Sequential Treatment ◽  
Hematologic Toxicity ◽  
Severe Toxicity ◽  
Peptide Receptor ◽  
Radio Therapy ◽  
Radiolabeled Somatostatin Analogues

81 Background: In metastatic neuroendocrine tumors (NET) peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogues (Lu-177-DOTATATE) and selective intra-arterial radio-therapy (SIRT) with Y-90-microspheres are increasingly used promising treatment options. Rarely patients have been treated with sequential use of both treatment modalities . Severe adverse effects are rare and mainly concern hematologic changes and development of prolonged cytopenias . There is no data about possible cumulative side effects particularly regarding hematologic toxicity in the case of sequential use of both treatments. Methods: 5 Patients with hepatic metastasized NET treated both with SIRT and PRRT during 2010 - 2019 were included. Average time interval between treatment of y90 and PRRT was 2.5 years. All of them were treated with y90 before PRRT. Average treatment with Y90 was 3 doses. Results: In the follow up Platelets (159 to 89), leukocytes (7.5 to 3.7) and hemoglobin (13 to 11.6 ) decreased significantly, LFTs, bilirubin and creatinine did not change significantly. No severe toxicity (Grade 3 or 4) was experienced. 80 % of the patients showed decreasing blood counts after the therapies and was prolonged for average of 9 months. Conclusions: In metastatic neuroendocrine tumors (NET) sequential treatment with peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogues (Lu-177-DOTATATE) after selective intra-arterial radio-therapy (SIRT) with Y-90-microspheres is possible and well tolerated except for hematological toxicity.

Mutant PPM1D- and TP53-Driven Hematopoiesis Populates the Hematopoietic Compartment in Response to Peptide Receptor Radionuclide Therapy

2022 ◽  
Author(s):  
Abhay Singh ◽  
Nuria Mencia-Trinchant ◽  
Elizabeth A. Griffiths ◽  
Alaa Altahan ◽  
Mahesh Swaminathan ◽  
...  
Keyword(s):  
Allele Frequency ◽  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Risk Mitigation ◽  
Peptide Receptor Radionuclide Therapy ◽  
Variant Allele ◽  
Hematologic Toxicity ◽  
Variant Allele Frequency ◽  
Blood Samples ◽  
Peptide Receptor

PURPOSE Hematologic toxic effects of peptide receptor radionuclide therapy (PRRT) can be permanent. Patients with underlying clonal hematopoiesis (CH) may be more inclined to develop hematologic toxicity after PRRT. However, this association remains understudied. MATERIALS AND METHODS We evaluated pre- and post-PRRT blood samples of patients with neuroendocrine tumors. After initial screening, 13 cases of interest were selected. Serial blood samples were obtained on 4 of 13 patients. Genomic DNA was analyzed using a 100-gene panel. A variant allele frequency cutoff of 1% was used to call CH. RESULT Sixty-two percent of patients had CH at baseline. Persistent cytopenias were noted in 64% (7 of 11) of the patients. Serial sample analysis demonstrated that PRRT exposure resulted in clonal expansion of mutant DNA damage response genes ( TP53, CHEK2, and PPM1D) and accompanying cytopenias in 75% (3 of 4) of the patients. One patient who had a normal baseline hemogram and developed persistent cytopenias after PRRT exposure showed expansion of mutant PPM1D (variant allele frequency increased to 20% after exposure from < 1% at baseline). In the other two patients, expansion of mutant TP53, CHEK2, and PPM1D clones was also noted along with cytopenia development. CONCLUSION The shifts in hematopoietic clonal dynamics in our study were accompanied by emergence and persistence of cytopenias. These cytopenias likely represent premalignant state, as PPM1D-, CHEK2-, and TP53-mutant clones by themselves carry a high risk for transformation to therapy-related myeloid neoplasms. Future studies should consider CH screening and longitudinal monitoring as a key risk mitigation strategy for patients with neuroendocrine tumors receiving PRRT.

scholarly journals Somatostatin receptor endoradiotherapy of neuroendocrine tumors: experience in Hungarian patients

2011 ◽  
Vol 152 (10) ◽  
pp. 392-397 ◽  
Author(s):  
Péter Reismann ◽  
Zoltán Kender ◽  
Gabriella Dabasi ◽  
Lídia Sréter ◽  
Károly Rácz ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Peptide Receptor Radionuclide Therapy ◽  
Somatostatin Analogues ◽  
Theoretical Background ◽  
Neuroendocrine Cells ◽  
Peptide Receptor ◽  
The University

Beside conventional therapies for the treatment of neuroendocrine tumors, a new therapeutical approach, peptide receptor radionuclide therapy has been developed recently. There are two important features which make this therapy feasible: somatostatin receptors are strongly over-expressed in most neuroendocrine tumors resulting in a high tumor-to-background ratio and internalization of the somatostatin-receptor complex in neuroendocrine cells. Due to these features, neuroendocrine tumors can be treated with radiolabelled somatostatin analogues. For peptide receptor radionuclide therapy, somatostatin analogues are conjugated to a chelator that can bind a radionuclide. The most frequently used radionuclides for neuroendocrine tumor treatment are the β-emitter Yttrium-90 (90Y) and the β+γ emitter Lutetium-177 (177Lu). Candidates for somatostatin receptor endoradiotherapy are patients with progressive, metastatic, somatostatin-receptor positive neuroendocrine tumors. Many patients have been successively treated with this approach: according to international results major remission can be achieved in 25% of the cases. Although this therapy is still unavailable in Hungary, Hungarian patients can be treated with somatostatin receptor endoradiotherapy with financial support from the National Health Fund in a co-operation with the University of Basel since 2005. During the past 5 years, 51 Hungarian patients have been treated with this therapy. This review briefly summarizes the theoretical background, indications, effectiveness and side effects of somatostatin receptor endoradiotherapy and the authors present the first data obtained from Hungarian patients. Orv. Hetil., 2011, 152, 392–397.

scholarly journals Predictive and Prognostic Impact of Blood-Based Inflammatory Biomarkers in Patients with Gastroenteropancreatic Neuroendocrine Tumors Commencing Peptide Receptor Radionuclide Therapy

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 504
Author(s):  
Fiona Ohlendorf ◽  
Rudolf Werner ◽  
Christoph Henkenberens ◽  
Tobias Ross ◽  
Hans Christiansen ◽  
...  
Keyword(s):  
Treatment Response ◽  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Somatostatin Receptor ◽  
Peptide Receptor Radionuclide Therapy ◽  
Tumor Burden ◽  
Inflammatory Biomarkers ◽  
Whole Body ◽  
Prognostic Impact ◽  
Peptide Receptor

Tumor microenvironment inflammation contributes to the proliferation and survival of malignant cells, angiogenesis, metastasis, subversion of adaptive immunity, and reduced treatment response. We aimed to evaluate the early predictive and prognostic significance of markers of systemic inflammation in patients receiving somatostatin-receptor targeted peptide receptor radionuclide therapy (PRRT). This retrospective observational cohort study included 33 patients with advanced gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) treated with PRRT. Pretreatment blood-based inflammatory biomarkers, e.g., Creactive protein levels (CRP), white blood cell count (WBC), and absolute neutrophil count (ANC), were documented and inflammation indexes, e.g., neutrophil-lymphocyte ratio (NLR) and Platelet × CRP multiplier (PCM), were calculated. Tumor burden was determined using [68Ga]GaDOTATATE PET/CT before enrollment and every 2 cycles thereafter until progression. Therapy response was assessed using RECIST 1.1, including its volumetric modification. Inflammatory biomarkers and inflammatory indexes demonstrated marked heterogeneity among patients, and were significantly higher in non-responders (e.g., CRP (P < 0.001), ANC (P = 0.002), and PCM (P < 0.001)). Change in whole-body tumor burden after two cycles of PRRT was significantly associated with CRP (P = 0.0157) and NLR (P = 0.0040) in multivariate regression analysis. A cut-off of 2.5 mg/L for CRP (AUC = 0.84, P = 0.001) revealed a significant outcome difference between patients with adversely high vs. low CRP (median PFS 508 days vs. not yet reached (HR = 4.52; 95% CI, 1.27 to 16.18; P = 0.02)). Tumor-driven systemic inflammatory networks may be associated with treatment response, change in tumor burden, and prognosis in patients with GEPNETs receiving PRRT.

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