Preview

Russian Journal of Spine Surgery (Khirurgiya Pozvonochnika)

Advanced search

The role of denosumab in the complex treatment of giant cell tumor of the spine: reducing of local recurrence rate, surgery time and blood loss

https://doi.org/10.14531/ss2021.4.81-90

Abstract

Objective. To assess the effect of the combined treatment method including preoperative denosumab therapy on the results of treatment of patients with giant cell tumors of the spine.

Material and Methods. A single-center retrospective-prospective study of a series of clinical cases included 15 patients with giant cell tumors of vertebrae. The average follow-up period was 56 months. A total of 11 patients received denosumab therapy according to the following scheme: 120 mg subcutaneously on the 1st, 8th, 15th and 28th days of the first month and then once every 28 days. Surgical options included marginal resection, segmental resection, or en-bloc resection with or without spinal reconstruction/stabilization. In the case of locally advanced and inoperable disease, long-term therapy with denosumab was carried out until the disease progressed or serious adverse events appeared.

Results. Thoracic vertebrae were involved in 7 (46.6 %) of 15 cases, lumbar in 4 (26.7 %) and cervical in 4 (26.7 %). Local recurrence rate after surgery alone was 40 % (2/5), average time to recurrence onset was 4.5 months. No relapses were observed after combined treatment performed in four patients. Disease progression during long-term denosumab therapy for inoperable disease recurrence was not recorded (0/7). The average number of denosumab injections before surgery and during long-term therapy was 15 and 24 injections, respectively. Denosumab therapy allows reducing the duration of surgery and the volume of blood loss.

Conclusion. Combined therapy of giant cell vertebral tumor allows to reduce the risk of recurrence of the disease, as well as to reduce surgery duration and blood loss. Long-term continuous therapy for inoperable cases allows achieving long-term stabilization of the effect. Due to the rarity of giant cell tumors of the spine, a further prospective recruitment of patients is required to study the efficacy and safety of combined therapies.

About the Authors

Anastasia Alekseevna Tararykova
N.N. Blokhin National Medical Research Center of Oncology 24 Kashirskoe shosse, Moscow, 115478, Russia
Russian Federation

oncologist of the Oncology Department of Surgical Methods of Treatment No. 1 of the General Oncology Department of the Research Institute of Clinical Oncology n.a. Acad. N.N. Trapeznikov



Aleksandr Aleksandrovich Fedenko
National Medical Research Radiological Center 3 2nd Botkinsky passage, Moscow, 125284, Russia
Russian Federation

DMSc, Chief of Medical Oncology Department



Elmar Rasimogly Musaev
N.N. Blokhin National Medical Research Center of Oncology 24 Kashirskoe shosse, Moscow, 115478, Russia
Russian Federation

DMSc, Professor, Chief of the Oncology Department of Surgical Methods of Treatment No. 9 of the General Oncology Department of the Research Institute of Clinical Oncology n.a. Acad. N.N. Trapeznikov



Aslan Kamraddinovich Valiev
N.N. Blokhin National Medical Research Center of Oncology 24 Kashirskoe shosse, Moscow, 115478, Russia
Russian Federation

MD, PhD, Chief of the General Oncology Department of the Research Institute of Clinical Oncology n.a. Acad. N.N. Trapeznikov



Ruslan Magomedovich Kabardaev
N.N. Blokhin National Medical Research Center of Oncology 24 Kashirskoe shosse, Moscow, 115478, Russia
Russian Federation

surgeon, oncologist of the Oncology Department of Surgical Methods of Treatment No. 9 of the General Oncology Department of the Research Institute of Clinical Oncology n.a. Acad. N.N. Trapeznikov



Kirill Aleksandrovich Borzov
N.N. Blokhin National Medical Research Center of Oncology 24 Kashirskoe shosse, Moscow, 115478, Russia
Russian Federation

surgeon, oncologist of the Oncology Department of Surgical Methods of Treatment No. 9 of the General Oncology Department of the Research Institute of Clinical Oncology n.a. Acad. N.N. Trapeznikov



Valeria Igorevna Melnikova
N.N. Blokhin National Medical Research Center of Oncology 24 Kashirskoe shosse, Moscow, 115478, Russia
Russian Federation

oncologist, pathologist, Pathomorphology Department of the Research Institute of Clinical Oncology n.a. Acad. N.N. Trapeznikov



References

1. Kallen ME, Hornick JL. The 2020 WHO Classification: What’s new in sift tissue tumor pathology? Am J Surg Pathol. 2021;45:e1–e23. DOI: 10.1097/PAS.0000000000001552.

2. Baena-Ocampo L del C, Ramirez-Perez E, Linares-Gonzalez LM, Delgado-Chavez R. Epidemiology of bone tumors in Mexico City: retrospective clinicopathologic study of 566 patients at a referral institution. Ann Diagn Pathol. 2009;13:16–21. DOI: 10.1016/j.anndiagpath.2008.07.005.

3. Werner M. Giant cell tumour of bone: morphological, biological and histogenetical aspects. Int Orthop. 2006;30:484–489. DOI: 10.1007/s00264-006-0215-7.

4. Salunke AA, Chen Y, Chen X, Tan JH, Singh G, Tai BC, Khin LW, Puhaindran ME. Does pathological fracture affect the rate of local recurrence in patients with a giant cell tumour of bone?: a meta-analysis. Bone Joint J. 2015:97–B:1566–1571. DOI: 10.1302/0301-620X.97B11.35326.

5. Harrop JS, Schmidt MH, Boriani S, Shaffrey CI. Aggressive «benign» primary spine neoplasms: osteoblastoma, aneurysmal bone cyst, and giant cell tumor. Spine. 2009;34(22 Suppl):S39–S47. DOI: 10.1097/brs.0b013e3181ba0024.

6. Charest-Morin R, Fisher CG, Varga PP, Gokaslan ZL, Rhines LD, Reynolds JJ, Dekutoski MB, Quraishi NA, Bilsky MH, Fehlings MG, Chou D, Germscheid NM, Luzzati A, Boriani S. En bloc resection versus intralesional surgery in the treatment of giant cell tumor of the spine. Spine. 2017;42:1383–1390. DOI: 10.1097/BRS.0000000000002094.

7. Luksanapruksa P, Buchowski JM, Singhatanadgige W, Bumpass DB. Systematic review and meta-analysis of en bloc vertebrectomy compared with intralesional resection for giant cell tumors of the mobile spine. Global Spine J. 2016;6:798–803. DOI: 10.1055/s-0036-1579746.

8. Karras NA, Polgreen LE, Ogilvie C, Manivel JC, Skubitz KM, Lipsitz E. Denosumab treatment of metastatic giant-cell tumor of bone in a 10-year-old girl. J Clin Oncol. 2013;31:e200–e202. DOI: 10.1200/JCO.2012.46.4255.

9. Rutkowski P, Ferrari S, Grimer RJ, Stalley PD, Dijkstra SPD, Pienkowski A, Vaz G, Wunder JS, Seeger LL, Feng A, Roberts ZJ, Bach BA. Surgical downstaging in an open-label phase ii trial of denosumab in patients with giant cell tumor of bone. Ann Surg Oncol. 2015;22:2860–2868. DOI: 10.1245/s10434-015-4634-9.

10. Zhang J, Wang X, Lin F, Xu G., Wu H, Duan J, Mao M, Zhang C. Survival and prognostic factors analyses in malignant giant cell tumor of bone: Preprint. 2019:1–21. DOI: 10.21203/rs.2.12960/v1.

11. Goldschlager T, Dea N, Boyd M, Reynolds J, Patel S, Rhines LD, Mendel E, Pacheco M, Ramos E, Mattei TA, Fisher CG. Giant cell tumors of the spine: has denosumab changed the treatment paradigm? J Neurosurg Spine. 2015;22:526–533. DOI: 10.3171/2014.10.SPINE13937.

12. Dubory A, Missenard G, Domont J, Court C. Interest of denosumab for the treatment of giant-cells tumors and aneurysmal bone cysts of the spine. About nine cases. Spine. 2016;41:E654–E660. DOI: 10.1097/BRS.0000000000001350.

13. Charest-Morin R, Boriani S, Fisher CG, Patel SR, Kawahara N, Mendel E, Bettegowda C, Rhines LD. Benign tumors of the spine: Has new chemotherapy and interventional radiology changed the treatment paradigm? Spine. 2016;41 Suppl 20:S178–S185. DOI: 10.1097/BRS.0000000000001818.

14. Yonezawa N, Murakami H, Kato S, Takeuchi A, Tsuchiya H. Giant cell tumor of the thoracic spine completely removed by total spondylectomy after neoadjuvant denosumab therapy. Eur Spine J. 2017;26(Suppl 1):236–242. DOI: 10.1007/s00586-017-5086-7.

15. Luksanapruksa P, Buchowski JM, Singhatanadgige W, Rose PC, Bumpass DB. Management of spinal giant cell tumors. Spine J. 2016;16:259–269. DOI: 10.1016/j.spinee.2015.10.045.

16. Rockberg J, Bach BA, Amelio J, Hernandez RK, Sobocki P, Engellau J, Bauer HCF, Liede A. Incidence trends in the diagnosis of giant cell tumor of bone in Sweden since 1958. J Bone Joint Surg Am. 2015;97:1756–1766. DOI: 10.2106/JBJS.O.00156.

17. Amelio JM, Rockberg J, Hernandez RK, Sobocki P, Stryker S, Bach BA, Engellau J, Liede A. Population-based study of giant cell tumor of bone in Sweden

18. (1983–2011). Cancer Epidemiol. 2016;42:82–89. DOI: 10.1016/j.canep.2016.03.014.

19. Gouin F, Dumaine V. Local recurrence after curettage treatment of giant cell tumors in peripheral bones: retrospective study by the GSF-GETO (French Sarcoma and Bone Tumor Study Groups). Orthop Traumatol Surg Res. 2013;99(6 Suppl):S313–S318. DOI: 10.1016/j.otsr.2013.07.006.

20. Усиков В.Д., Пташников Д.А. Реконструктивные операции в комплексной терапии больных с гигантоклеточной опухолью позвоночника // Травматология и ортопедия России. 2005. Т. 1. № 34. С. 12–15. [Usikov VD, Ptashnikov DA. Reconstructive operations in the complex therapy of patients with giant cell tumor of the spine. Traumatology and Orthopedics of Russia. 2005;1(34):12–15. In Russian].

21. Rock MG, Sim FH, Unni KK, Witrak GA, Frassica FJ, Schray MF, Beabout JW, Dahlin DC. Secondary malignant giant-cell tumor of bone. Clinicopathological assessment of nineteen patients. J Bone Joint Surg Am. 1986;68:

22. –1079. DOI: 10.2106/00004623-198668070-00016.

23. Bertoni F, Bacchini P, Staals EL. Malignancy in giant cell tumor of bone. Cancer. 2003;97:2520–2529. DOI: 10.1002/cncr.11359.

24. Shimizu T, Murakami H, Demura S, Kato S, Yoshioka K, Yokogawa N, Kawahara N, Tomita K, Tsuchiya H. Total en bloc spondylectomy for primary tumors of the lumbar spine. Medicine (Baltimore). 2018;97:e12366. DOI: 10.1097/MD.0000000000012366.

25. Mohanty SP, Pai Kanhangad M, Kundangar R. The extended posterior approach for resection of sacral tumours. Eur Spine J. 2019;28:1461–1467. DOI: 10.1007/s00586-018-5834-3.

26. Yokogawa N, Murakami H, Demura S, Kato S, Yoshioka K, Shimizu T, Oku N, Kitagawa R, Tsuchiya H. Total spondylectomy for Enneking stage III giant cell tumor of the mobile spine. Eur Spine J. 2018;27:3084–3091. DOI: 10.1007/s00586-018-5761-3.

27. Басанкин И.В., Порханов В.А., Тахмазян К.К., Кононенко В.Б., Штрауб В.В., Ситник С.Д., Зяблова Е.И., Пашкова И.А., Федорченко А.Н., Бухтояров А.Ю. Гигантоклеточная опухоль грудного отдела позвоночника. Клинический случай эффективной радикальной спондилэктомии трех позвонков // Инновационная медицина Кубани. 2017. Т. 2. № 6. С. 21–27. [Basankin IV, Porhanov VA, Takhmazyan KK, Kononenko VB, Schtraub VV, Sitnik SD, Zyablova EI, Pashkova IA, Fedorchenko AN, Bukhtoyarov AY. Giant cell tumor of thoracic spine. A clinical case of efficient radical spondylectomy of three vertebral bodies. Innovatsionnaya Meditsina Kubani. 2017;2(6):21–27. In Russian].

28. Thomas DM. RANKL, denosumab, and giant cell tumor of bone. Curr Opin Oncol. 2012;24:397–403. DOI: 10.1097/CCO.0b013e328354c129.

29. Rutkowski P, Gaston L, Borkowska A, Stacchiotti S, Gelderblom H, Baldi GG, Palmerini E, Casali P, Gronchi A, Parry M, Campanacci DA, Scoccianti G, Wagrodzki M, Ferrari S, Dijkstra S, Pienkowski A, Grimer R. Denosumab treatment of inoperable or locally advanced giant cell tumor of bone – Multicenter analysis outside clinical trial. Eur J Surg Oncol. 2018;44:1384–1390. DOI: 10.1016/j.ejso.2018.03.020.

30. Thomas D, Henshaw R, Skubitz K, Chawla S, Staddon A, Blay JY, Roudier M, Smith J, Ye Z, Sohn W, Dansey R, Jun S. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010;11:275–280. DOI: 10.1016/S1470-2045(10)70010-3.

31. Ueda T, Morioka H, Nishida Y, Kakunaga S, Tsuchiya H, Matsumoto Y, Asami Y, Inoue T, Yoneda T. Objective tumor response to denosumab in patients with giant cell tumor of bone: a multicenter phase II trial. Ann. Oncol. 2015;26:2149–2154. DOI: 10.1093/annonc/mdv307.

32. Chawla S, Blay JY, Le Cesne A, Reichardt P, Gelderblom H, Grimer RJ, Choy E, Skubitz K, Seeger L, Schuetze SM, Henshaw R, Dai T, Jandial D, Palmerini E. Denosumab in patients with giant-cell tumour of bone: a multicentre, open-label, phase 2 study. Lancet Oncol. 2019;20:1719–1729. DOI: 10.1016/S1470-2045(19)30663-1.

33. Chawla S, Henshaw R, Seeger L, Choy E, Blay JY, Ferrari S, Kroep J, Grimer R, Reichardt P, Rutkowski P, Schuetze SM, Skubitz K, Staddon A, Thomas D, Qian Y, Jacobs I. Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol. 2013;14:901–908. DOI: 10.1016/S1470-2045(13)70277-8.

34. Bukata SV, Blay JY, Rutkowski P, Skubitz K, Henshaw R, Seeger L, Dai T, Jandial D, Chawla S. Denosumab treatment for giant cell tumor of the spine including the sacrum. Spine. 2021;46:277–284. DOI: 10.1097/BRS.0000000000003728.

35. Urakawa H, Yonemoto T, Matsumoto S, Takagi T, Asanuma K, Watanuki M, Takemoto A, Naka N, Matsumoto Y, Kawai A, Kunisada T, Kubo T, Emori M, Hiraga H, Hatano H, Tsukushi S, Nishida Y, Akisue T, Morii T, Takahashi M, Nagano A, Yoshikawa H, Sato K, Kawano M, Hiraoka K, Tanaka K, Iwamoto Y, Ozaki T. Clinical outcome of primary giant cell tumor of bone after curettage with or without perioperative denosumab in Japan: from a questionnaire for JCOG 1610 study. World J Surg Oncol. 2018;16:160. DOI: 10.1186/s12957-018-1459-6.

36. Mattei TA, Ramos E, Rehman AA, Shaw A, Patel SR, Mendel E. Sustained long-term complete regression of a giant cell tumor of the spine after treatment with denosumab. Spine J. 2014;14:e15–e21. DOI: 10.1016/j.spinee.2014.02.019.

37. Lin P, Lin N, Teng W, Wang SD, Pan WB, Huang X, Yan XB, Liu M, Li HY, Li BH, Sun LL, Wang Z, Zhou XZ, Ye ZM. Recurrence of giant cell tumor of the spine after resection: a report of 10 cases. Orthop Surg. 2018;10:107–114. DOI: 10.1111/os.12375.


Review

For citations:


Tararykova A.A., Fedenko A.A., Musaev E.R., Valiev A.K., Kabardaev R.M., Borzov K.A., Melnikova V.I. The role of denosumab in the complex treatment of giant cell tumor of the spine: reducing of local recurrence rate, surgery time and blood loss. Russian Journal of Spine Surgery (Khirurgiya Pozvonochnika). 2021;18(4):81-90. https://doi.org/10.14531/ss2021.4.81-90



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


ISSN 1810-8997 (Print)
ISSN 2313-1497 (Online)