The role of neoadjuvant denosumab in the treatment of aneurysmal bone cysts: a case series and review of the literature

Alexandra M. Giantini-LarsenDepartments of Neurosurgery and
Department of Neurosurgery, Weill Cornell Medical Center, New York, New York

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Vikram B. ChakravarthyDepartments of Neurosurgery and

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Ori BarzilaiDepartments of Neurosurgery and

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William Christopher NewmanDepartments of Neurosurgery and

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Leonard WexlerPediatrics, Memorial Sloan Kettering Cancer Center, New York; and

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Mark H. BilskyDepartments of Neurosurgery and
Department of Neurosurgery, Weill Cornell Medical Center, New York, New York

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OBJECTIVE

Aneurysmal bone cysts (ABCs) are benign cystic lesions most commonly occurring in the long bones of pediatric patients. Spinal ABCs may be difficult to resect given their invasive, locally destructive nature, proximity to critical structures such as the spinal cord, and their intrinsic hypervascularity, for which complete embolization is often constrained by radiculomedullary segmental feeders. Denosumab, a monoclonal antibody that binds the receptor activator of nuclear factor kappa B (NF-κB) ligand, has been utilized in the treatment of ABCs most often as a rescue therapy for recurrent disease. Here, the authors present 3 cases of neoadjuvant denosumab use in surgically unresectable tumors to calcify and devascularize the lesions, allowing for safer, more complete resection.

METHODS

This is a single-center, retrospective case series treated at a tertiary care cancer center. The authors present 3 cases of spinal ABC treated with neoadjuvant denosumab.

RESULTS

All 3 patients experienced calcification, size reduction, and a significant decrease in the vascularity of their ABCs on denosumab therapy. None of the patients developed new neurological deficits while on denosumab. Subsequently, all underwent resection. One patient continued denosumab during the immediate postoperative period because a subtotal resection had been performed, with stabilization of the residual disease. No complications were associated with denosumab administration.

CONCLUSIONS

The use of denosumab in unresectable ABCs can cause calcification and devascularization, making safe resection more likely.

ABBREVIATIONS

ABC = aneurysmal bone cyst; RANKL = receptor activator of NF-κB ligand; NF-κB = nuclear factor kappa B.
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Images from Chiang et al. (pp 595–601).

  • 1

    Jaffe HL, Lichtenstein L. Solitary unicameral bone cyst: with emphasis on the Roentgen picture, the pathologic appearance and the pathogenesis. Arch Surg. 1942;44(6):10041025.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2

    Park HY, Yang SK, Sheppard WL, et al. Current management of aneurysmal bone cysts. Curr Rev Musculoskelet Med. 2016;9(4):435444.

  • 3

    Copley L, Dormans JP. Benign pediatric bone tumors. Evaluation and treatment. Pediatr Clin North Am. 1996;43(4):949966.

  • 4

    Ye Y, Pringle LM, Lau AW, et al. TRE17/USP6 oncogene translocated in aneurysmal bone cyst induces matrix metalloproteinase production via activation of NF-kappaB. Oncogene. 2010;29(25):36193629.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Doss VT, Weaver J, Didier S, Arthur AS. Serial endovascular embolization as stand-alone treatment of a sacral aneurysmal bone cyst. J Neurosurg Spine. 2014;20(2):234238.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Boriani S, Lo SF, Puvanesarajah V, et al. Aneurysmal bone cysts of the spine: treatment options and considerations. J Neurooncol. 2014;120(1):171178.

  • 7

    Liu JK, Brockmeyer DL, Dailey AT, Schmidt MH. Surgical management of aneurysmal bone cysts of the spine. Neurosurg Focus. 2003;15(5):E4.

  • 8

    George HL, Unnikrishnan PN, Garg NK, Sampath JS, Bass A, Bruce CE. Long-term follow-up of Ethibloc injection in aneurysmal bone cysts. J Pediatr Orthop B. 2009;18(6):375380.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Feigenberg SJ, Marcus RB Jr, Zlotecki RA, Scarborough MT, Berrey BH, Enneking WF. Megavoltage radiotherapy for aneurysmal bone cysts. Int J Radiat Oncol Biol Phys. 2001;49(5):12431247.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Chawla S, Henshaw R, Seeger L, et al. 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(9):901908.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Thomas DM. RANKL, denosumab, and giant cell tumor of bone. Curr Opin Oncol. 2012;24(4):397403.

  • 12

    Lange T, Stehling C, Fröhlich B, et al. Denosumab: a potential new and innovative treatment option for aneurysmal bone cysts. Eur Spine J. 2013;22(6):14171422.

  • 13

    Skubitz KM, Peltola JC, Santos ER, Cheng EY. Response of aneurysmal bone cyst to denosumab. Spine (Phila Pa 1976). 2015;40(22):E1201E1204.

  • 14

    Pelle DW, Ringler JW, Peacock JD, et al. Targeting receptor-activator of nuclear kappaB ligand in aneurysmal bone cysts: verification of target and therapeutic response. Transl Res. 2014;164(2):139148.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    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 (Phila Pa 1976). 2016;41(11):E654E660.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Fadavi P, Arefpour AM, Hariri R, Vasheghani M, Garousi M, Taghizadeh-Hesary F. Dramatic response of aneurysmal bone cyst to denosumab: case report and literature review. Clin Case Rep. 2021;9(10):e04993.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Ghermandi R, Terzi S, Gasbarrini A, Boriani S. Denosumab: non-surgical treatment option for selective arterial embolization resistant aneurysmal bone cyst of the spine and sacrum. Case report. Eur Rev Med Pharmacol Sci. 2016;20(17):36923695.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Patel RS, Dhamne CA, Gopinathan A, Kumar N, Kumar N. Denosumab: a potential treatment option for aneurysmal bone cyst of the atlas. Eur Spine J. 2018;27(suppl 3):494500.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Raux S, Bouhamama A, Gaspar N, et al. Denosumab for treating aneurysmal bone cysts in children. Orthop Traumatol Surg Res. 2019;105(6):11811185.

  • 20

    Kulkarni AG, Patel A. Denosumab: a potential new treatment option for recurrent aneurysmal bone cyst of the spine. SICOT J. 2019;5:10.

  • 21

    Dürr HR, Grahneis F, Baur-Melnyk A, et al. Aneurysmal bone cyst: results of an off label treatment with denosumab. BMC Musculoskelet Disord. 2019;20(1):456.

  • 22

    Palmerini E, Ruggieri P, Angelini A, et al. Denosumab in patients with aneurysmal bone cysts: a case series with preliminary results. Tumori. 2018;104(5):344351.

  • 23

    Yamagishi T, Kawashima H, Ogose A, et al. Receptor-activator of nuclear kappaB ligand expression as a new therapeutic target in primary bone tumors. PLoS One. 2016;11(5):e0154680.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Kurucu N, Akyuz C, Ergen FB, et al. Denosumab treatment in aneurysmal bone cyst: evaluation of nine cases. Pediatr Blood Cancer. 2018;65(4):e26926.

  • 25

    Laskowski LK, Goldfarb DS, Howland MA, Kavcsak K, Lugassy DM, Smith SW. A RANKL wrinkle: denosumab-induced hypocalcemia. J Med Toxicol. 2016;12(3):305308.

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