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Nuklearmedizin 2021; 60(02): 99-105
DOI: 10.1055/a-1332-8230
Original Article

Cardiotoxicity and cardiac monitoring following the use of radiotheranostics agents including 177Lu-PSMA for prostate cancer and 177Lu-DOTATATE for neuroendocrine tumors

Kardiotoxizität und kardiale Überwachung nach dem Einsatz von Radiotheranostika einschließlich 177Lu-PSMA bei Prostatakrebs und 177Lu-DOTATATE bei neuroendokrinen Tumoren
Esmail Jafari
1   The Persian Gulf Nuclear Medicine Research Center, Department of Molecular Imaging and Radionuclide Therapy (MIRT), Bushehr Medical University Hospital, Bushehr University of Medical Sciences, Bushehr, Iran
,
Abdul Latif Amini
2   Bushehr Heart Medical center, Bushehr University of Medical Sciences, Bushehr, Iran
,
Hojjat Ahmadzadehfar
3   Department of Nuclear Medicine, Klinikum Westfalen, Dortmund, Germany
,
Dara Bagheri
4   Department of Fisheries, Faculty of Agriculture and Natural Resources, Persian Gulf University, Bushehr, Iran
,
Majid Assadi
1   The Persian Gulf Nuclear Medicine Research Center, Department of Molecular Imaging and Radionuclide Therapy (MIRT), Bushehr Medical University Hospital, Bushehr University of Medical Sciences, Bushehr, Iran
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Abstract

Background The aim of this study was to determine the probable cardiotoxicity following radionuclide therapy (RNT), specifically peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE and radioligand therapy (RLT) with 177Lu-PSMA by evaluation of serum troponin I and cardiac profile change during a follow-up time.

Materials and Methods Patients with prostate cancer and neuroendocrine tumours (NETs) referred for PRRT and RLT, respectively, were enrolled in this study. The cardiac profiles of the patients were evaluated by a cardiologist and a cardiac history was obtained from all patients. Also, troponin I was measured before and 48 hours after treatment.

Results In this retrospective study for assessment of RLT associated cardiotoxicity, 24 patients were evaluated with a median age of 64 years (27–99 years) including 13 NET patients and 11 prostate cancer patients. Patients were followed up for 4 to 31 months which no cardiovascular problem was observed. In evaluation of troponin I, 39 RNT cycles were evaluated. In all patients, the value of troponin I was in normal range. In all patients, the median values of serum troponin I before and after treatment were 0.2 ± 0.02 (range: 0.00–0.42) and 0.28 ± 0.02 (range: 0.00–0.46) ng/ml, respectively (p > 0.05). In the prostate cancer patients, the median values of serum troponin I before and after treatment were 0.26 ± 0.04 (0.04–0.42) and 0.30 ± 0.04 (0.00–0.41) ng/ml, respectively (p > 0.05). In the NET patients, the median values of serum troponin I before and after treatment were 0.18 ± 0.03 (0.00–0.42) and 0.17 ± 0.03 (0.00–0.46) ng/ml, respectively (p > 0.05).

Conclusion PRRT with 177Lu-DOTATATE and RLT with 177Lu-PSMA as emerging therapeutic modalities have no significant cardiotoxicity. However, further well-designed studies are recommended.

Zusammenfassung

Hintergrund Ziel dieser Studie war die Bestimmung der voraussichtlichen Kardiotoxizität nach Radionuklidtherapie (RNT), speziell der Peptidrezeptor-Radionuklidtherapie (PRRT) mit 177Lu-DOTATATE und der Radioligandentherapie (RLT) mit 177Lu-PSMA durch Bewertung von Serum-Troponin I und der kardialen Profilveränderung während einer Nachbeobachtungszeit.

Material und Methoden Patienten mit Prostatakrebs und neuroendokrinen Tumoren (NETs), die zur PRRT bzw. RLT überwiesen wurden, wurden in diese Studie eingeschlossen. Die kardialen Profile der Patienten wurden von einem Kardiologen beurteilt und von allen Patienten wurde eine kardiale Anamnese erhoben. Außerdem wurde Troponin I vor und 48 Stunden nach der Behandlung gemessen.

Ergebnisse In dieser retrospektiven Studie zur Beurteilung der RLT-assoziierten Kardiotoxizität wurden 24 Patienten mit einem medianen Alter von 64 Jahren (27–99 Jahre) untersucht, darunter 13 NET-Patienten und 11 Prostatakrebspatienten. Die Patienten wurden für 4–31 Monate nachbeobachtet, wobei keine Herz-Kreislauf-Probleme beobachtet wurden. Bei der Bewertung von Troponin I wurden 39 RNT-Zyklen ausgewertet. Bei allen Patienten lag der Wert von Troponin I im Normalbereich. Bei allen Patienten lagen die medianen Werte von Serum-Troponin I vor und nach der Behandlung bei 0,2 ± 0,02 (Bereich: 0,00–0,42) bzw. 0,28 ± 0,02 (Bereich: 0,00–0,46) ng/ml (p > 0,05). Bei den Prostatakrebspatienten betrugen die medianen Werte von Serum-Troponin I vor und nach der Behandlung 0,26 ± 0,04 (0,04–0,42) bzw. 0,30 ± 0,04 (0,00–0,41) ng/ml (p > 0,05). Bei den NET-Patienten betrugen die Medianwerte von Serum-Troponin I vor und nach der Behandlung 0,18 ± 0,03 (0,00–0,42) bzw. 0,17 ± 0,03 (0,00–0,46) ng/ml (p > 0,05).

Schlussfolgerung PRRT mit 177Lu-DOTATATE und RLT mit 177Lu-PSMA als neue therapeutische Modalitäten weisen keine signifikante Kardiotoxizität auf. Weitere gut konzipierte Studien werden jedoch empfohlen.

Key words

troponin - cardiovascular toxicity - peptide receptor radionuclide therapy (PRRT) - 177Lu-DOTATATE - radioligand therapy (RLT) - 177Lu-PSMA

Schlüsselwörter

Troponin - kardiovaskuläre Toxizität - Peptidrezeptor-Radionuklidtherapie (PRRT) - 177Lu-DOTATATE - Radioligandentherapie (RLT) - 177Lu-PSMA


Publication History

Received: 20 September 2020

Accepted: 08 December 2020

Article published online:
18 January 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Fuster V, Voûte J. MDGs: chronic diseases are not on the agenda. The Lancet 2005; 366: 1512-1514
    CrossrefPubMedGoogle Scholar
  • 2 Chen Z, Ai D. Cardiotoxicity associated with targeted cancer therapies. Molecular and clinical oncology 2016; 4 (05) 675-681
    CrossrefPubMedGoogle Scholar
  • 3 Herrmann J, Lerman A, Sandhu NP. et al. Evaluation and management of patients with heart disease and cancer: cardio-oncology. Elsevier; 2014
    Google Scholar
  • 4 Van Leeuwen FE, Ng AK. Long-term risk of second malignancy and cardiovascular disease after Hodgkin lymphoma treatment. Hematology 2016; 2016: 323-330
    CrossrefPubMedGoogle Scholar
  • 5 Caron J, Nohria A. Cardiac Toxicity from Breast Cancer Treatment: Can We Avoid This?. Current Oncology Reports 2018; 20: 1-8
    CrossrefPubMedGoogle Scholar
  • 6 Atkins KM, Rawal B, Chaunzwa TL. et al. Cardiac Radiation Dose, Cardiac Disease, and Mortality in Patients With Lung Cancer. J Am Coll Cardiol 2019; 73: 2976-2987
    CrossrefPubMedGoogle Scholar
  • 7 Fuchs CS, Tomasek J, Yong CJ. et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. The Lancet 2014; 383: 31-39
    CrossrefPubMedGoogle Scholar
  • 8 Marmagkiolis K, Finch W, Tsitlakidou D. et al. Radiation Toxicity to the Cardiovascular System. Current Oncology Reports 2016; 18: 1-8
    CrossrefPubMedGoogle Scholar
  • 9 Galper SL, Yu JB, Mauch PM. et al. Clinically significant cardiac disease in patients with Hodgkin lymphoma treated with mediastinal irradiation. Blood 2011; 117 (02) 412-418
    CrossrefPubMedGoogle Scholar
  • 10 Grönberg H. Prostate cancer epidemiology. The Lancet 2003; 361: 859-864
    CrossrefPubMedGoogle Scholar
  • 11 Warner RRP. Enteroendocrine tumors other than carcinoid: a review of clinically significant advances. Gastroenterology 2005; 128 (06) 1668-1684
    CrossrefPubMedGoogle Scholar
  • 12 Kulke MH, Anthony LB, Bushnell DL. et al. NANETS treatment guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas. Pancreas 2010; 39 (06) 735
    CrossrefPubMedGoogle Scholar
  • 13 Assadi M, Rezaei S, Jafari E. et al. Potential application of lutetium-177-labeled prostate-specific membrane antigen-617 radioligand therapy for metastatic castration-resistant prostate cancer in a limited resource environment: Initial clinical experience after 2 years. 2020 19(1). 15-20
    PubMedGoogle Scholar
  • 14 Ahmadzadehfar H, Eppard E, Kurpig S. et al. Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer. Oncotarget 2016; 7 (11) 12477-12488
    CrossrefPubMedGoogle Scholar
  • 15 Ballinger JRJTBjor. Theranostic radiopharmaceuticals: established agents in current use. 2018 91(1091). 20170969
    PubMedGoogle Scholar
  • 16 Yordanova A, Eppard E, Kürpig S. et al. Theranostics in nuclear medicine practice. 2017 10. 4821
    PubMedGoogle Scholar
  • 17 Assadi M, Ahmadzadehfar HJWJoNM. 177Lu-DOTATATE and 177Lu-prostate-specific membrane antigen therapy in a patient with advanced metastatic radioiodine-refractory differentiated thyroid cancer after failure of tyrosine kinase inhibitors treatment. 2019 18(4). 406
    PubMedGoogle Scholar
  • 18 Kendi AT, Halfdanarson TR, Packard A. et al. Therapy with 177Lu-DOTATATE: Clinical implementation and impact on care of patients with neuroendocrine tumors. 2019 213(2). 309-317
    PubMedGoogle Scholar
  • 19 Abou Jokh Casas E, Pubul Núñez V, Anido-Herranz U. et al. Evaluation of 177Lu-Dotatate treatment in patients with metastatic neuroendocrine tumors and prognostic factors. World journal of gastroenterology 2020; 26 (13) 1513-1524
    CrossrefPubMedGoogle Scholar
  • 20 Brabander T, Van der Zwan WA, Teunissen JJM. et al. Long-term efficacy, survival, and safety of [177Lu-DOTA0, Tyr3] octreotate in patients with gastroenteropancreatic and bronchial neuroendocrine tumors. Clinical Cancer Research 2017; 23 (16) 4617-4624
    CrossrefPubMedGoogle Scholar
  • 21 Abdel-Rahman O, Fouad M. Risk of cardiovascular toxicities in patients with solid tumors treated with sunitinib, axitinib, cediranib or regorafenib: an updated systematic review and comparative meta-analysis. Critical reviews in oncology/hematology 2014; 92 (03) 194-207
    CrossrefPubMedGoogle Scholar
  • 22 CHEN Z, AI D. Cardiotoxicity associated with targeted cancer therapies. Molecular and Clinical Oncology 2016; 4: 675-681
    CrossrefPubMedGoogle Scholar
  • 23 Des Guetz G, Uzzan B, Chouahnia K. et al. Cardiovascular toxicity of anti-angiogenic drugs. Targeted oncology 2011; 6 (04) 197-202
    CrossrefPubMedGoogle Scholar
  • 24 Donnellan E, Phelan D, Mccarthy CP. et al. Radiation-induced heart disease: A practical guide to diagnosis and management. Cleveland Clinic Journal of Medicine 2016; 83: 914-922
    CrossrefPubMedGoogle Scholar
  • 25 Groarke JD, Choueiri TK, Slosky D. et al. Recognizing and managing left ventricular dysfunction associated with therapeutic inhibition of the vascular endothelial growth factor signaling pathway. Current treatment options in cardiovascular medicine 2014; 16 (09) 335
    CrossrefPubMedGoogle Scholar
  • 26 Spetz J, Moslehi J, Sarosiek K. Radiation-Induced Cardiovascular Toxicity: Mechanisms, Prevention, and Treatment. Current Treatment Options in Cardiovascular Medicine 2018; 20 (04) 31
    CrossrefPubMedGoogle Scholar
  • 27 Zamorano JL, Lancellotti P, Rodriguez Muñoz D. et al. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines:  The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). European Heart Journal 2016; 37 (36) 2768-2801
    CrossrefPubMedGoogle Scholar
  • 28 Limat S, Daguindau E, Cahn JY. et al. Incidence and risk‐factors of CHOP/R‐CHOP‐related cardiotoxicity in patients with aggressive non‐Hodgkin’s lymphoma. Journal of clinical pharmacy and therapeutics 2014; 39 (02) 168-174
    CrossrefPubMedGoogle Scholar
  • 29 Oeffinger KC, Mertens AC, Sklar CA. et al. Chronic health conditions in adult survivors of childhood cancer. New England Journal of Medicine 2006; 355 (15) 1572-1582
    CrossrefPubMedGoogle Scholar
  • 30 Kimmick GG, Lenihan DJ, Sawyer DB. et al. Cardio-Oncology: The Clinical Overlap of Cancer and Heart Disease. Springer; 2017
    CrossrefGoogle Scholar
  • 31 Luminari S, Montanini A, Caballero D. et al. Nonpegylated liposomal doxorubicin (MyocetTM) combination (R-COMP) chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL): results from the phase II EUR018 trial. Annals of Oncology 2010; 21 (07) 1492-1499
    CrossrefPubMedGoogle Scholar
  • 32 Cardinale D, Sandri MT, Martinoni A. et al. Left ventricular dysfunction predicted by early troponin I release after high-dose chemotherapy. J Am Coll Cardiol 2000; 36 (02) 517-522
    CrossrefPubMedGoogle Scholar
  • 33 Bergsma H, van Lom K, Raaijmakers MH. et al. Persistent hematologic dysfunction after peptide receptor radionuclide therapy with 177Lu-DOTATATE: incidence, course, and predicting factors in patients with gastroenteropancreatic neuroendocrine tumors. Journal of Nuclear Medicine 2018; 59 (03) 452-458
    CrossrefPubMedGoogle Scholar
  • 34 Ramesh S, Kudachi S, Basu S. PRRT with 177Lu-DOTATATE in Carcinoid Heart Disease: a contraindication or a promising treatment approach bettering chances for corrective surgery?. Journal of Nuclear Medicine Technology 2018; DOI: jnmt.118.210179.
    CrossrefPubMedGoogle Scholar
  • 35 Iacovelli R, Ciccarese C, Bria E. et al. The cardiovascular toxicity of abiraterone and enzalutamide in prostate cancer. Clinical genitourinary cancer 2018; 16 (03) e645-e653
    CrossrefPubMedGoogle Scholar
  • 36 Moreira RB, Debiasi M, Francini E. et al. Differential side effects profile in patients with mCRPC treated with abiraterone or enzalutamide: a meta-analysis of randomized controlled trials. 2017 8(48). 84572
    PubMedGoogle Scholar
  • 37 Mackey JR, Martin M, Pienkowski T. et al. Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial. The Lancet Oncology 2013; 14 (01) 72-80
    CrossrefPubMedGoogle Scholar
  • 38 Papaetis GS, Syrigos KN. Sunitinib: a multitargeted receptor tyrosine kinase inhibitor in the era of molecular cancer therapies. BioDrugs: clinical immunotherapeutics, biopharmaceuticals and gene therapy 2009; 23 (06) 377-389
    CrossrefPubMedGoogle Scholar
  • 39 Kucharz J, Michalowska-Kaczmarczyk A, Zygulska AL. et al. Bradycardia as a rare symptom of cisplatin cardiotoxicity: a case report. 2016 11(3). 2297-2299
    PubMedGoogle Scholar
  • 40 Hendifar AE, Delpassand ES, Kittleson MM. et al. Cardiac Toxicity in a Patient Receiving Peptide Receptor Radionuclide Therapy. Pancreas 2018; 47 (08) e55-e56
    CrossrefPubMedGoogle Scholar