Abstract
Purpose
This study was performed to evaluate the efficacy of 177Lu-labelled peptide receptor radionuclide therapy (PRRT) in patients with inoperable or metastatic neuroendocrine tumours (NETs).
Methods
Systematic searches of MEDLINE and EMBASE databases were performed using the keywords of “neuroendocrine”, “177Lu” and “prognosis”. All published studies of neuroendocrine tumours treated with 177Lu-labelled radiopharmaceuticals and evaluated with either Response Evaluation Criteria in Solid Tumours (RECIST) 1.0 or Southwest Oncology Group (SWOG) criteria or both were included. If there was more than one published study from the same institution, only one report with the information most relevant to this study was included. Each response criteria group was analysed for disease response rates and disease control rates, defined as the percentages of patients with complete response (CR) + partial response (PR), and CR + PR + stable disease (SD), respectively, to a therapeutic intervention in clinical trials of anticancer agents. The pooled proportions are presented with both a fixed-effects model and random-effects model.
Results
Six studies with 473 patients (4 in RECIST criteria group with 356 patients, 3 in SWOG criteria group with 375 patients and 1 in both groups) were included. The RECIST criteria group demonstrated disease response rates ranging between 17.6 and 43.8 % with a pooled effect of 29 % [95 % confidence interval (CI) 24–34 %]. Disease control rates ranged from 71.8 to 100 %. The random-effects model showed an average disease control rate of 81 % (95 % CI 71–91 %). The SWOG criteria group demonstrated disease response rates ranging between 7.0 and 36.5 % with a pooled effect of 23 % (95 % CI 11–38 %). Disease control rates ranged from 73.9 to 89.1 %. The random-effects model showed an average disease control rate of 82 % (95 % CI 71–91 %).
Conclusion
177Lu-labelled PRRT is an effective treatment option for patients with inoperable or metastatic NETs.
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References
Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 2008;26:3063–72. doi:10.1200/JCO.2007.15.4377.
Bodei L, Mueller-Brand J, Baum RP, Pavel ME, Hörsch D, O’Dorisio MS, et al. The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2013;40:800–16. doi:10.1007/s00259-012-2330-6.
Krenning EP, Kooij PP, Bakker WH, Breeman WA, Postema PT, Kwekkeboom DJ, et al. Radiotherapy with a radiolabeled somatostatin analogue, [111In-DTPA-D-Phe1]-octreotide. A case history. Ann N Y Acad Sci 1994;733:496–506.
Otte A, Jermann E, Behe M, Goetze M, Bucher HC, Roser HW, et al. DOTATOC: a powerful new tool for receptor-mediated radionuclide therapy. Eur J Nucl Med 1997;24:792–5.
Kwekkeboom DJ, Bakker WH, Kam BL, Teunissen JJ, Kooij PP, de Herder WW, et al. Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA(0), Tyr3]octreotate. Eur J Nucl Med Mol Imaging 2003;30:417–22. doi:10.1007/s00259-002-1050-8.
Romer A, Seiler D, Marincek N, Brunner P, Koller MT, Ng QK, et al. Somatostatin-based radiopeptide therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]-TOC in neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2014;41:214–22. doi:10.1007/s00259-013-2559-8.
de Jong M, Breeman WA, Valkema R, Bernard BF, Krenning EP. Combination radionuclide therapy using 177Lu- and 90Y-labeled somatostatin analogs. J Nucl Med 2005;46 Suppl 1:13S–7S.
Prasad V, Bodei L, Kidd M, Modlin IM. Whither peptide receptor radionuclide therapy for neuroendocrine tumors: an Einsteinian view of the facts and myths. Eur J Nucl Med Mol Imaging 2014;41:1825–30. doi:10.1007/s00259-014-2780-0.
Valkema R, Pauwels SA, Kvols LK, Kwekkeboom DJ, Jamar F, de Jong M, et al. Long-term follow-up of renal function after peptide receptor radiation therapy with (90)Y-DOTA(0), Tyr(3)-octreotide and (177)Lu-DOTA(0), Tyr(3)-octreotate. J Nucl Med 2005;46 Suppl 1:83S–91S.
Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010;25:603–5. doi:10.1007/s10654-010-9491-z.
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557–60. doi:10.1136/bmj.327.7414.557.
Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 2009;151:264–9. W64.
Bodei L, Cremonesi M, Grana CM, Fazio N, Iodice S, Baio SM, et al. Peptide receptor radionuclide therapy with (177)Lu-DOTATATE: the IEO phase I-II study. Eur J Nucl Med Mol Imaging 2011;38:2125–35. doi:10.1007/s00259-011-1902-1.
Delpassand ES, Samarghandi A, Zamanian S, Wolin EM, Hamiditabar M, Espenan GD, et al. Peptide receptor radionuclide therapy with 177Lu-DOTATATE for patients with somatostatin receptor-expressing neuroendocrine tumors: the first US phase 2 experience. Pancreas 2014;43:518–25. doi:10.1097/MPA.0000000000000113.
Paganelli G, Sansovini M, Ambrosetti A, Severi S, Monti M, Scarpi E, et al. 177 Lu-Dota-octreotate radionuclide therapy of advanced gastrointestinal neuroendocrine tumors: results from a phase II study. Eur J Nucl Med Mol Imaging 2014;41:1845–51. doi:10.1007/s00259-014-2735-5.
Ezziddin S, Attassi M, Yong-Hing CJ, Ahmadzadehfar H, Willinek W, Grünwald F, et al. Predictors of long-term outcome in patients with well-differentiated gastroenteropancreatic neuroendocrine tumors after peptide receptor radionuclide therapy with 177Lu-octreotate. J Nucl Med 2014;55:183–90. doi:10.2967/jnumed.113.125336.
van Vliet EI, Krenning EP, Teunissen JJ, Bergsma H, Kam BL, Kwekkeboom DJ. Comparison of response evaluation in patients with gastroenteropancreatic and thoracic neuroendocrine tumors after treatment with [177Lu-DOTA0, Tyr3]octreotate. J Nucl Med 2013;54:1689–96. doi:10.2967/jnumed.112.117408.
Claringbold PG, Brayshaw PA, Price RA, Turner JH. Phase II study of radiopeptide 177Lu-octreotate and capecitabine therapy of progressive disseminated neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2011;38:302–11. doi:10.1007/s00259-010-1631-x.
Danthala M, Kallur KG, Prashant GR, Rajkumar K, Raghavendra RM. (177)Lu-DOTATATE therapy in patients with neuroendocrine tumours: 5 years' experience from a tertiary cancer care centre in India. Eur J Nucl Med Mol Imaging 2014;41:1319–26. doi:10.1007/s00259-014-2710-1.
Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S. The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas 2010;39:707–12. doi:10.1097/MPA.0b013e3181ec124e.
Pavel M, Baudin E, Couvelard A, Krenning E, Öberg K, Steinmüller T, et al. ENETS Consensus Guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology 2012;95:157–76. doi:10.1159/000335597.
Wang SE, Su CH, Kuo YJ, Shyr YM, Li AF, Chen TH, et al. Comparison of functional and nonfunctional neuroendocrine tumors in the pancreas and peripancreatic region. Pancreas 2011;40:253–9. doi:10.1097/MPA.0b013e3181f94cc4.
Kulke MH, Shah MH, Benson 3rd AB, Bergsland E, Berlin JD, Blaszkowsky LS, et al. Neuroendocrine tumors, version 1.2015. J Natl Compr Canc Netw 2015;13:78–108.
van der Zwan WA, Bodei L, Mueller-Brand J, de Herder WW, Kvols LK, Kwekkeboom DJ. GEPNETs update: radionuclide therapy in neuroendocrine tumors. Eur J Endocrinol 2015;172:R1–8. doi:10.1530/EJE-14-0488.
Bodei L, Kidd M, Baum RP, Modlin IM. PRRT: defining the paradigm shift to achieve standardization and individualization. J Nucl Med 2014;55:1753–6. doi:10.2967/jnumed.114.143974.
Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, et al. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0, Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008;26:2124–30. doi:10.1200/JCO.2007.15.2553.
Rolleman EJ, Valkema R, de Jong M, Kooij PP, Krenning EP. Safe and effective inhibition of renal uptake of radiolabelled octreotide by a combination of lysine and arginine. Eur J Nucl Med Mol Imaging 2003;30:9–15. doi:10.1007/s00259-002-0982-3.
Bodei L, Kidd M, Paganelli G, Grana CM, Drozdov I, Cremonesi M, et al. Long-term tolerability of PRRT in 807 patients with neuroendocrine tumours: the value and limitations of clinical factors. Eur J Nucl Med Mol Imaging 2015;42:5–19. doi:10.1007/s00259-014-2893-5.
Cremonesi M, Botta F, Di Dia A, Ferrari M, Bodei L, De Cicco C, et al. Dosimetry for treatment with radiolabelled somatostatin analogues. A review. Q J Nucl Med Mol Imaging 2010;54:37–51.
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This study was not funded by any organization.
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This article does not contain any studies with human participants or animals performed by any of the authors.
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Seong-Jang Kim and Kyoungjune Pak contributed equally to this work.
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Kim, SJ., Pak, K., Koo, P.J. et al. The efficacy of 177Lu-labelled peptide receptor radionuclide therapy in patients with neuroendocrine tumours: a meta-analysis. Eur J Nucl Med Mol Imaging 42, 1964–1970 (2015). https://doi.org/10.1007/s00259-015-3155-x
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DOI: https://doi.org/10.1007/s00259-015-3155-x