Top

European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-07-2019 | Neuroblastoma | Original Article

Dosimetry-based high-activity therapy with ¹³¹I-metaiodobenzylguanidine (¹³¹I-mIBG) and topotecan for the treatment of high-risk refractory neuroblastoma

Authors: Jose Genolla, Trinidad Rodriguez, Pablo Minguez, Ricardo Lopez-Almaraz, Veronica Llorens, Aizpea Echebarria

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 7/2019

Abstract

Purpose

Patients with high-risk neuroblastoma have an increased risk of recurrence and relapse of disease and a very poor prognosis. ¹³¹I-metaiodobenzylguanidine (¹³¹I-mIBG) in combination with topotecan as a radiosensitizer can be an effective and relatively well-tolerated agent for the treatment of refractory neuroblastoma. The aim of this retrospective study was to evaluate response and outcome of combined therapy with ¹³¹I-mIBG and topotecan.

Methods

Ten patients, between 3 and 20 years of age, were included. Nine patients had been refractory to several lines of chemotherapy and radiotherapy. One patient with a very high-risk neuroblastoma had received only induction therapy. Response was graded according to the International Neuroblastoma Staging System.

Results

Regarding treatment response, two patients achieved complete remission, one with relapse at 16 months, five achieved a partial remission, four showed progression at between 1 and 18 months; two showed stable disease with progression at between 1 and 5 months, and one showed progressive disease. Eight of the ten patients died with overall survival between 4 and 63 months, and two patients were still alive without disease at the time of this report: 52 and 32 months (patient had received only induction therapy). Acute and subacute adverse effects were mainly haematological, and one patient developed a differentiated thyroid cancer.

Conclusion

In patients with high-risk refractory neuroblastoma, administration of high activities of ¹³¹I-mIBG in combination with topotecan was found to be an effective therapy, increasing overall survival and progression-free survival. Further studies including a larger number of patients and using ¹³¹I-mIBG for first-line up-front therapy are warranted.

Available only for authorised users

Brodeur GM, Pritchard J, Berthold F, Carlsen NL, Castel V, Castelberry RP, et al. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol. 1993;1:1466–77.CrossRef

Schmidt ML, Lal A, Seeger RC, Maris JM, Shimada H, O'Leary M, et al. Favorable prognosis for patients 12 to 18 months of age with stage 4 nonamplified MYCN neuroblastoma: a Children's Cancer Group study. J Clin Oncol. 2005;23:6474–80. https://doi.org/10.1200/JCO.2005.05.183.CrossRefPubMed

Seeger RC, Brodeur GM, Sather H, Dalton A, Siegel SE, Wong KY, et al. Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. N Engl J Med. 1985;313:1111–6. https://doi.org/10.1056/NEJM198510313131802.CrossRefPubMed

Attiyeh EF, London WB, Mosse YP, Wang Q, Winter C, Khazi D, et al. Chromosome 1p and 11q deletions and outcome in neuroblastoma. N Engl J Med. 2005;353:2243–53. https://doi.org/10.1056/NEJMoa052399.CrossRefPubMed

Shimada H, Chatten J, Newton WA Jr, Sachs N, Hamoudi AB, Chiba T, et al. Histopathologic prognostic factors in neuroblastic tumours: definition of subtypes of ganglioneuroblastoma and an age-linked classification of neuroblastomas. J Natl Cancer Inst. 1984;73:405–16.CrossRefPubMed

Matthay KK, Villablanca JG, Seeger RC, Stram DO, Harris RE, Ramsay NK, et al. Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. Children’s Cancer Group. N Engl J Med. 1999;341:1165–73. https://doi.org/10.1056/NEJM199910143411601.CrossRefPubMed

Matthay KK, Reynolds CP, Seeger RC, Shimada H, Adkins ES, Haas-Kogan D, et al. Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a Children’s Oncology Group study. J Clin Oncol. 2009;27:1007–13. https://doi.org/10.1200/JCO.2007.13.8925.CrossRefPubMedPubMedCentral

Carlin S, Mairs RJ, McCluskey AG, Tweddle DA, Sprigg A, Estlin C, et al. Development of a real-time polymerase chain reaction assay for prediction of the uptake of meta-[(131)]iodobenzylguanidine by neuroblastoma tumours. Clin Cancer Res. 2003;9:3338–44.PubMed

Wieland DM, Brown LE, Tobes MC, Rogers WL, Marsh DD, Mangner TJ, et al. Imaging the primate adrenal medulla with I-123 and I-131 metalodobenzylguanidine. Concise communication. J Nucl Med. 1981;22:358–64.PubMed

10.

Kolby L, Bernhardt P, Levin-Jakobsen AM, Johanson V, Wängberg B, Ahlman H, et al. Uptake of meta-iodobenzylguanidine in neuroendocrine tumours is mediated by vesicular monoamine transporters. Br J Cancer. 2003;89:1383–8. https://doi.org/10.1038/sj.bjc.6601276.CrossRefPubMedPubMedCentral

11.

Smets LA, Janssen M, Rutgers M, Ritzen K, Buitenhuis C. Pharmacokinetics and intracellular distribution of the tumor-targeted radiopharmaceutical m-iodo-benzylguanidine in SK-N-SH neuroblastoma and PC-12 pheochromocytoma cells. Int J Cancer. 1991;48:609–15.CrossRefPubMed

12.

Sisson J, Shapiro B, Beierwaltes WH, Nakajo M, Glowniak J, Mangner T. Treatment of malignant pheochromocytoma with a new radio-pharmaceutical. Trans Assoc Am Phys. 1983;96:209–17.PubMed

13.

Vetter H, Fischer M, Müller-Rensing R, Vetter W, Winterberg B. 131-I-meta-iodobenzylguanidine in treatment of malignant phaeochromocytomas. Lancet. 1983;2:107.CrossRefPubMed

14.

Beierwaltes WH. Treatment of neuroblastoma with 131I-mIBG: dosimetric problems and perspectives. Med Pediatr Oncol. 1987;15:188–91.CrossRefPubMed

15.

Garaventa A, Bellagamba O, Lo Piccolo MS, Milanaccio C, Lanino E, Bertolazzi L, et al. 131I-Metaiodobenzylguanidine (131I-MIBG) therapy for residual neuroblastoma: a mono-institutional experience with 43 patients. Br J Cancer. 1999;81:1378–84. https://doi.org/10.1038/sj.bjc.6694223.CrossRefPubMedPubMedCentral

16.

Mastrangelo S, Tornesello A, Diociaiuti L, Pession A, Prete A, Rufini V, et al. Treatment of advanced neuroblastoma: feasibility and therapeutic potential of a novel approach combining 131-I-MIBG and multiple drug chemotherapy. Br J Cancer. 2001;84:460–4. https://doi.org/10.1054/bjoc.2000.1645.CrossRefPubMedPubMedCentral

17.

Matthay KK, Tan JC, Villablanca JG, Yanik GA, Veatch J, Franc B, et al. Phase I dose escalation of iodine-131-metaiodobenzylguanidine with myeloablative chemotherapy and autologous stem-cell transplantation in refractory neuroblastoma: a New Approaches To Neuroblastoma Therapy Consortium study. J Clin Oncol. 2006;24:500–6. https://doi.org/10.1200/JCO.2005.03.6400.CrossRefPubMed

18.

Gaze MN, Chang YC, Flux GD, Mairs RJ, Saran FH, Meller ST. Feasibility of dosimetry-based high-dose 131I-meta-iodobenzylguanidine with topotecan as a radiosensitizer in children with metastatic neuroblastoma. Cancer Biother Radiopharm. 2005;20:195–9.CrossRefPubMed

19.

Buckley SE, Saran FH, Gaze MN, Chittenden S, Partridge M, Lancaster D, et al. Dosimetry for fractionated (131)I-mIBG therapies in patients with primary resistant high-risk neuroblastoma: preliminary results. Cancer Biother Radiopharm. 2007;22:105–12. https://doi.org/10.1089/cbr.2007.301.CrossRefPubMed

20.

Ferry I, Kolesnikov-Gauthier H, Oudoux A, Cougnenc O, Schleiermacher G, Michon J, et al. Feasibility of busulfan melphalan and stem cell rescue after 131I-MIBG and topotecan therapy for refractory or relapsed metastatic neuroblastoma: the French experience. J Pediatr Hematol Oncol. 2018;40:426–32.CrossRefPubMed

21.

Simon T, Längler A, Harnischmacher U, Frühwald MC, Jorch N, Claviez A, et al. Topotecan, cyclophosphamide, and etoposide (TCE) in the treatment of high-risk neuroblastoma. Results of a phase-II trial. J Cancer Res Clin Oncol. 2007;133:653–61. https://doi.org/10.1007/s00432-007-0216-y.CrossRefPubMed

22.

Vassal G, Pondarré C, Capelli C, Terrier-Lacombe MJ, Boland I, Morizet J, et al. DNA-topoisomerase I, a new target for the treatment of neuroblastoma. Eur J Cancer. 1997;33:2011–5.CrossRefPubMed

23.

Mattem MR, Hofmann GA, McCabe FL, Johnson RK. Synergistic cell killing by ionizing radiation and topoisomerase I inhibitor topotecan (SK&F 104864). Cancer Res. 1991;51:5813–6.

24.

Miyamoto S, Huang TT, Wuerzberger-Davis S, Bornmann WG, Pink JJ, Tagliarino C, et al. Cellular and molecular responses to topoisomerase I poisons. Exploiting synergy for improved radiotherapy. Ann N Y Acad Sci. 2000;922:274–92.

25.

McCluskey AG, Boyd M, Gaze MN, Mairs RJ. [131I]MIBG and topotecan: a rationale for combination therapy for neuroblastoma. Cancer Lett. 2005;228:221–7. https://doi.org/10.1016/j.canlet.2004.11.062.CrossRefPubMed

26.

McCluskey AG, Boyd M, Pimlott SL, Babich JW, Gaze MN, Mairs RJ. Experimental treatment of neuroblastoma using [131I]metaiodobenzylguanidine and topotecan in combination. Br J Radiol. 2008;81:S28–35.CrossRefPubMed

27.

Loevinger R, Budinger T, Watson E. MIRD primer for absorbed dose calculations. New York: Society of Nuclear Medicine; 1988.

28.

Dewaraja YK, Ljungberg M, Green AJ, Zanzonico PB, Frey EC. MIRD pamphlet no. 24: guidelines for quantitative 131I SPECT in dosimetry applications. J Nucl Med. 2013;54:2182–8. https://doi.org/10.2967/jnumed.113.122390.CrossRefPubMedPubMedCentral

29.

Matthay KK, Huberty JP, Hattner RS, Ablin AR, Engelstad BL, Zoger S. Efficacy and safety of 131I-metaiodobenzylguanidine therapy for patients with refractory neuroblastoma. J Nucl Biol Med. 1991;35:244–7.PubMed

30.

Buckley SE, Chittenden SJ, Saran FH, Meller ST, Flux GD. Whole-body dosimetry for individualized treatment planning of 131I-mIBG radionuclide therapy for neuroblastoma. J Nucl Med. 2009;50:1518–24. https://doi.org/10.2967/jnumed.109.064469.CrossRefPubMed

31.

Sudbrock F, Schmidt M, Simon T, Eschner W, Berthold F, Schicha H. Dosimetry for 131I-MIBG therapies in metastatic neuroblastoma, phaeochromocytoma and paraganglioma. Eur J Nucl Med Mol Imaging. 2010;37:1279–90. https://doi.org/10.1007/s00259-010-1391-7.CrossRefPubMed

32.

Vaidyanathan G, Zalutsky MR. No-carrier-added synthesis of meta-131I-iodobenzylguanidine. Appl Radiat Isot. 1993;44:621–8.CrossRefPubMed

33.

Barrett JA, Joyal JL, Hillier SM, Maresca KP, Femia FJ, Kronauge JF, et al. Comparison of high-specific-activity Ultratrace 123/131I-MIBG and carrier-added 123/131I-MIBG on efficacy, pharmacokinetics, and tissue distribution. Cancer Biother Radiopharm. 2010;25(3):299–308. https://doi.org/10.1089/cbr.2009.0695.CrossRefPubMed

34.

Vallabhajosula S, Nikolopoulou A. Radioiodinated metaiodobenzylguanidine (MIBG): radiochemistry, biology, and pharmacology. Semin Nucl Med. 2011;41:324–33. https://doi.org/10.1053/j.semnuclmed.2011.05.003.CrossRefPubMed

35.

DuBois SG, Geier E, Batra V, Yee SW, Neuhaus J, Segal M, et al. Evaluation of norepinephrine transporter expression and metaiodobenzylguanidine avidity in neuroblastoma: a report from the Children’s Oncology Group. Int J Mol Imaging. 2012;2012:250834. https://doi.org/10.1155/2012/250834.CrossRefPubMedPubMedCentral

36.

Bleeker G, Schoot RA, Caron HN, Kraker J, Hoefnagel CA, van Eck BL, et al. Toxicity of upfront 131I-metaiodobenzylguanidine (131I-MIBG) therapy in newly diagnosed neuroblastoma patients: a retrospective analysis. Eur J Nucl Med Mol Imaging. 2013;40:1711–7. https://doi.org/10.1007/s00259-013-2510-z.CrossRefPubMedPubMedCentral

37.

Polishchuk AL, DuBois SG, Haas-Kogan D, Hawkins R, Matthay KK. Response, survival, and toxicity after Iodine-131-metaiodobenzylguanidine therapy for neuroblastoma in preadolescents, adolescents, and adults. Cancer. 2011;117:4286–93. https://doi.org/10.1002/cncr.25987.CrossRefPubMedPubMedCentral

38.

Ben-Arush MW, Ben Barak A, Bar-Deroma R, Ash S, Goldstein G, Golan H, et al. Targeted therapy with low doses of I-131-MIBG is effective for disease palliation in highly refractory neuroblastoma. Isr Med Assoc J. 2013;15:31–4.

39.

Troncone L, Rufini V, Riccardi R, Lasorella A, Mastrangelo R. The use of [131I]metaiodobenzylguanidine in the treatment of neuroblastoma after conventional therapy. J Nucl Biol Med. 1991;35:232–6.PubMed

40.

Wilson JS, Gains JE, Moroz V, Wheatley K, Gaze MN. A systematic review of 131I-metaiodobenzylguanidine molecular radiotherapy for neuroblastoma. Eur J Cancer. 2014;50:801–15. https://doi.org/10.1016/j.ejca.2013.11.016.CrossRefPubMed

41.

VERITAS. An international multicenter phase II randomised trial evaluating and comparing two intensification treatment strategies for metastatic neuroblastoma patients with a poor response to induction chemotherapy. A SIOPEN study. V1.1, 10 April 2017.

42.

Cristy M, Eckerman K. Specific absorbed sessions of energy at various ages from internal photon sources. ORNL/TM-8381/V1–V7. Oak Ridge: Oak Ridge National Laboratory; 1987.

43.

Mínguez P, Flux G, Genollá J, Guayambuco S, Delgado A, Fombellida JC, et al. Dosimetric results in treatments of neuroblastoma and neuroendocrine tumours with 131I-metaiodobenzylguanidine with implications for the activity to administer. Med Phys. 2015;42(7):3969–78. https://doi.org/10.1118/1.4921807.CrossRefPubMed

Title: Dosimetry-based high-activity therapy with 131I-metaiodobenzylguanidine (131I-mIBG) and topotecan for the treatment of high-risk refractory neuroblastoma
Authors: Jose Genolla
Trinidad Rodriguez
Pablo Minguez
Ricardo Lopez-Almaraz
Veronica Llorens
Aizpea Echebarria
Publication date: 01-07-2019
Publisher: Springer Berlin Heidelberg
Keywords: Neuroblastoma
Neuroblastoma
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 7/2019
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-019-04291-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Dosimetry-based high-activity therapy with ¹³¹I-metaiodobenzylguanidine (¹³¹I-mIBG) and topotecan for the treatment of high-risk refractory neuroblastoma

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 7/2019

One-stop shopping 18F-FDG PET/CT in a patient with vascular type Behçet’s disease

TSH suppression aggravates arterial inflammation — an 18F-FDG PET study in thyroid carcinoma patients

Chemoradiotherapy for locally advanced cervix cancer without aortic lymph node involvement: can we consider metabolic parameters of pretherapeutic FDG-PET/CT for treatment tailoring?

Exploratory radiomic features from integrated 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging are associated with contemporaneous metastases in oesophageal/gastroesophageal cancer

EANM Focus 1: one small step for two men, one giant leap for a specialty

Breaking an unhelpful circle, where innovation and regularia delay clinical practice for patient benefit