Preview

Russian Journal of Pediatric Hematology and Oncology

Advanced search

Clinical and biological characteristics of neuroblastoma in adolescents and young adults. Case study and literature review

https://doi.org/10.21682/2311-1267-2020-7-3-13-21

Abstract

Introduction. Neuroblastoma (NB) is the most common extracranial solid tumor in infants, but it is more rarely found in older children. Only 1–2 % of cases are registered in adolescents and young adults. The long-term prognosis in these patients is highly unfavorable due to indolent clinical course formed by peculiar biological characteristics of tumors. We publish a case study of 11 patients with NB older than 10 years at the time of diagnosis.

Case series description. In 2008 to 2020 a total of 11 adolescent and young adults patients with median age of 14 (10–28) years were treated in Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg. Seven of 11 patients had mediastinal neuroblastoma, in other cases the primary lesion was abdominal (n = 2), pelvic (n = 1), and in one case no primary lesion was defined. Ten of 11 patients had primary disseminated disease with lymph nodes (n = 5), bone (n = 5), bone marrow (n = 3), or hepatic (n = 1) metastases. Tumor morphology and cytogenetics were assessed in all patients, in 4 cases additional targeted sequencing of potentially pathogenic genes was performed. All patients received chemotherapy and local control measures according to high-risk NB guidelines, in 7 of 11 cases additional chemotherapy regimens were used. Seven of 11 patients also received dose-intensive consolidation with autologous hemopoietic stem cell transplantation (auto-HSCT). In case of primary resistance MIBG-therapy, targeted or immunotherapy were used. In 6 cases tumor morphology corresponded to undifferentiated neuroblastoma, in 5 cases to ganglioneuroblastoma. Although all cases were high-risk, they mostly lacked high-risk biological features seen in younger patients. None had MYCN amplification, the cytogenetic assay yielded the following aberrations: +2 (n = 2), del1p (n = 1), g17q (n = 1). All patients, in whom the targeted sequencing was performed had pathogenic mutations: ATRX (in two patients 19 and 28 years at diagnosis), TP53 and PIK3CA, FBXW7. Nine of 11 patients had primary resistant disease, in 7 cases response was obtained on second or subsequent therapy lines. Two patients responded two chemoand targeted therapy combination, in 3 cases monoor combined immunotherapy yielded prolonged (16–32 months) response. Six of 7 auto-HSCT recipients developed a relapse. 6 out of 11 patients are currently alive. In 2 cases, a complete response is maintained according to scintigraphy with 123I-MIBG, lasting 86 and 14 months after completion of therapy.

Conclusions. NB is biologically different in adolescents and young adults. It is characterized by indolent clinical course with very high risk of late relapse. As most patients in this group are chemoresistant, the standard dose-intensive tactics may be less effective and perhaps more attention should be given to targeted and immunotherapy-based approaches.

About the Authors

I. V. Kazantsev
Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg, Ministry of Health of Russia
Russian Federation

Pediatric Oncologist 2nd Pediatric Transplant Department at Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, Assistant for Hematology, Transfusiology and Transpantation Chair ofI.P.PavlovSaint-PetersburgFirstStateMedicalUniversity

12 Rentgena St., Saint Petersburg, 197022



A. G. Gevorgyan
Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg, Ministry of Health of Russia
Russian Federation

Cand. of Sci. (Med.), Head of the 2nd Pediatric Transplant Department at Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, Assistant for Hematology, Transfusiology and Transpantation Chair atI.P.PavlovSaint-PetersburgFirstStateMedicalUniversity

12 Rentgena St., Saint Petersburg, 197022



T. V. Yukhta
Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg, Ministry of Health of Russia
Russian Federation

Pediatric Oncologist 2nd Pediatric Transplant Department at Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation

12 Rentgena St., Saint Petersburg, 197022

SPIN-code: 2552-7003



P. S. Tolkunova
Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg, Ministry of Health of Russia
Russian Federation

Pediatric Oncologist 2nd Pediatric Transplant Department at Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation

12 Rentgena St., Saint Petersburg, 197022



A. V. Kozlov
Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg, Ministry of Health of Russia
Russian Federation

Cand. of Sci. (Med.), Senior Research Associate, Associate Professor for Hematology, Transfusiology and Transpantation Chair atI.P.PavlovSaint-PetersburgFirstStateMedicalUniversity

12 Rentgena St., Saint Petersburg, 197022



D. A. Zvyagintseva
Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg, Ministry of Health of Russia
Russian Federation

Cand. of Sci. (Med.), Pediatric Oncologist 2nd Pediatric Transplant Department at Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation

12 Rentgena St., Saint Petersburg, 197022



M. S. Golenkova
Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg, Ministry of Health of Russia
Russian Federation

Pediatric Oncologist 2nd Pediatric Transplant Department at Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation

12 Rentgena St., Saint Petersburg, 197022



O. I. Bogdanova
Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg, Ministry of Health of Russia

Pediatric Oncologist 2nd Pediatric Transplant Department at Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation

12 Rentgena St., Saint Petersburg, 197022



A. N. Shvetsov
Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg, Ministry of Health of Russia

Head of Surgery Department at Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation

12 Rentgena St., Saint Petersburg, 197022



E. V. Morozova
Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg, Ministry of Health of Russia

Cand. of Sci. (Med.), Associate Professor for Hematology, Transfusiology and Transpantation Chair atI.P.PavlovSaint-PetersburgFirstStateMedicalUniversity

12 Rentgena St., Saint Petersburg, 197022



I. Yu. Nikolaev
Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg, Ministry of Health of Russia

Radiologist of the Department of X-ray Computed Tomography No. 1 atI.P.PavlovSaint-PetersburgFirstStateMedicalUniversity

12 Rentgena St., Saint Petersburg, 197022



S. A. Safonova
Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg, Ministry of Health of Russia

Cand. of Sci. (Med.), Pediatric Oncologist 2nd Pediatric Transplant Department at Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation

12 Rentgena St., Saint Petersburg, 197022



Yu. A. Punanov
Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg, Ministry of Health of Russia

Dr. of Sci. (Med.), Professor for Hematology, Transfusiology and Transpantation Chair atI.P.PavlovSaint-PetersburgFirstStateMedicalUniversity

12 Rentgena St., Saint Petersburg, 197022



L. S. Zubarovskaya
Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg, Ministry of Health of Russia

Dr. of Sci. (Med.), Professor for Hematology, Transfusiology and Transpantation Chair ofI.P.PavlovSaint-PetersburgFirstStateMedicalUniversity

12 Rentgena St., Saint Petersburg, 197022



B. V. Afanasyev
Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg, Ministry of Health of Russia

Dr. of Sci. (Med.), Professor, Director of Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, Head of Hematology, Transfusiology and Transpantation Chair at I.P. Pavlov Saint-Petersburg First State Medical University

12 Rentgena St., Saint Petersburg, 197022



References

1. Mossé Y.P., Deyell R.J., Berthold F., Nagakawara A., Ambros P.F., Monclair T., Cohn S.L., Pearson A.D., London W.B., Matthay K.K. Neuroblastoma in older children, adolescents and young adults: a report from the International Neuroblastoma Risk Group project. Pediatr Blood Cancer 2014;61(4):627–35. doi: 10.1002/pbc.24777.

2. Spix C., Pastore G., Sankila R., Stiler C.A., Steliarova-Foucher E. Neuroblastoma incidence and survival in European children (1978‒1997): report from the Automated Childhood Cancer Information System project. Eur J Cancer 2006;42(13):2081-91. doi: 10.1016/j.ejca.2006.05.008.

3. Cohn S.L., Pearson A.D., London W.B., Monclair T., Ambros P.F., Brodeur G.M., Faldum A., Hero B., Iehara T., Machin D., Mosseri V., Simon T., Garaventa A., Castel V., Matthay K.K. The International Neuroblastoma Risk Group (INRG) Classification System: An INRG Task Force Report. J Clin Oncol 2009;27(2):289‒97. doi: 10.1200/JCO.2008.16.6785.

4. Morgenstern D.A., Pötschger U., Moreno L., Papadakis V., Owens C., Ash S., Pasqualini C., Luksch R., Garaventa A., Canete A., Elliot M., Wieczorek A., Laureys G., Kogner P., Malis J., Ruud E., Beck-Popovic M., Schleiermacher G., Valteau-Couanet D., Ladenstein R. Risk stratification of high-risk metastatic neuroblastoma: A report from the HR-NBL-1/SIOPEN study. Pediatr Blood Cancer 2018;65(11):e27363. doi: 10.1002/pbc.27363.

5. Shinagawa T., Kitamura T., Katanoda K., Matsuda T., Ito Y., Sobue T. The incidence and mortality rates of neuroblastoma cases before and after the cessation of the mass screening program in Japan: A descriptive study. Int J Cancer 2017;140(3):618‒25. doi: 10.1002/ijc.30482.

6. Conte M., Parodi S., De Bernardi B., Milanaccio C., Mazzocco K., Angelini P., Viscardi E., Di Cataldo A., Luksch R., Haupt R. Neuroblastoma in adolescents: the Italian experience. Cancer 2006;106(6):1409‒17. doi: 10.1002/cncr.21751.

7. Duan X.F., Zhao Q. TERT-mediated and ATRX-mediated Telomere Maintenance and Neuroblastoma. J Pediatr Hematol Oncol 2018;40(1):1‒6. doi: 10.1097/MPH.0000000000000840.

8. Suzuki M., Kushner B.H., Kramer K., Basu E.M., Roberts S.S., Hammond W.J., LaQuaglia M.P., Wolden S.L., Cheung N.K.V., Modak S. Treatment and Outcome of Adult-Onset Neuroblastoma. Int J Cancer 2018;143(5):1249‒58. doi: 10.1002/ijc.31399.

9. Kazantsev I.V., Iukhta T.V., Gevorgian A.G., Tolkunova P.S., Shamin A.V., Baykov V.V., Vorobyov A.V., Kozlov A.V., Karsakova M.A., Kuga P.S., Shvetsov A.N., Morozova E.V., Safonova S.A., Punanov Yu.A., Zubarovskaya L.S., Afanasyev B.V. A long-term response to allogeneic hemopoietic stem cell transplantation from haploidentical donor and post-transplant therapy in an adolescent with primary resistant neuroblastoma. Cellular Therapy and Transplantation 2020;9(2):71‒6. doi: 10.18620/ctt-1866-8836-2020-9-2-71-77.

10. Suzuki M., Kushner B.H., Kramer K., Roberts S.S., LaQuaglia M.P., Cheung N.K.V., Modak S. Anti-GD2 immunotherapy in adults with high-risk neuroblastoma (HR-NB): The Memorial Sloan Kettering Cancer Center (MSKCC) experience. J Clin Oncol 2017;35(15_s):10550. doi: 10.1200/JCO.2017.35.15_suppl.10550.

11. Hertwig F., Peifer M., Fischer M. Telomere maintenance is pivotal for high-risk neuroblastoma. Cell Cycle 2016;15(3):311‒2. doi: 10.1080/15384101.2015.1125243.

12. Zeineldin M., Federico S., Chen X., Fan Y., Xu B., Steward E., Zhou X., Jeon J., Griffiths L., Nguyen R., Norrie J., Easton J., Mulder H., Yergeau D., Liu Y., Wu J., Van Ryn C., Naranjo A., Hogarty M.D., Kamiński M.M., Valentine M., Pruett-Miller S.M., Pappo A., Zhang J., Clay M.R., Bahrami A., Vogel P., Lee S., Shelat A., Sarthy J.F., Meers M.P., George R.E., Mardis E.R., Wilson R.K., Henikoff S., Downing J.R., Dyer M.A. MYCN amplification and ATRX mutations are incompatible in neuroblastoma. Nat Commun 2020;11(1):913. doi: 10.1038/s41467-020-14682-6.

13. Duan K., Dickson B.C., Marrano P., Thorner P.S., Chung C.T. Adult-onset neuroblastoma: Report of seven cases with molecular genetic characterization. Genes Chromosomes Cancer 2020;59(4):240‒8. doi: 10.1002/gcc.22826.

14. Ikegaki N., Shimada H; International Neuroblastoma Pathology Committee. Subgrouping of Unfavorable Histology Neuroblastomas With Immunohistochemistry Toward Precision Prognosis and Therapy Stratification. JCO Precis Oncol 2019;3:10.1200/PO.18.00312. doi: 10.1200/PO.18.00312.

15. Kazantsev I.V., Gevorgyan A.G., Yukhta T.V., Tolkunova P.S., Zvyagintseva D.A., Kozlov A.V., Golenkova M.S., Babenko E.V., Kuga P.S., Shvetsov A.N., Nikolaev I.Yu., Morozova E.V., Safonova S.A., Punanov Yu.A., Zubarovskaya L.S., Afanasyev B.V. The complex intensive therapy regimen as curative therapy in patients with primary-resistant and relapsed neuroblastoma: R.M. Gorbacheva Memorial Institute for Children Oncology, Hematology and Transplantation experience. Voprosy gematologii/onkologii i immunopatologii v pediatrii = Pediatric Hematology/Oncology and Immunopathology 2020;19(2):129‒40. (In Russ.). doi: 10.24287/1726-1708-2020-19-2-129-140.

16. Umpathy G., Mendoza-Garcia P., Hallberg B., Palmer R.H. Targeting anaplastic lymphoma kinase in neuroblastoma. APMIS 2019;127(5):288‒302. doi: 10.1111/apm.12940.

17. Vasseur A., Cabel L., Geiss R., Schleiermacher G., Pierron G., Kamal M., Jehanno N., Bataillon G., Guinebretiere J.M., Bozec L. Efficacy of Lorlatinib in Primary Crizotinib-Resistant Adult Neuroblastoma Harboring ALKY1278S Mutation. JCO Precis Oncol 2019;3:1‒5. doi: 10.1200/PO.18.00396.


Review

For citations:


Kazantsev I.V., Gevorgyan A.G., Yukhta T.V., Tolkunova P.S., Kozlov A.V., Zvyagintseva D.A., Golenkova M.S., Bogdanova O.I., Shvetsov A.N., Morozova E.V., Nikolaev I.Yu., Safonova S.A., Punanov Yu.A., Zubarovskaya L.S., Afanasyev B.V. Clinical and biological characteristics of neuroblastoma in adolescents and young adults. Case study and literature review. Russian Journal of Pediatric Hematology and Oncology. 2020;7(3):13-21. (In Russ.) https://doi.org/10.21682/2311-1267-2020-7-3-13-21

Views: 761


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2311-1267 (Print)
ISSN 2413-5496 (Online)
X