Skip to main content

Advertisement

Log in

Focused versus conventional radiotherapy in spinal oncology: is there any difference in fusion rates and pseudoarthrosis?

  • Clinical Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Introduction

Radiotherapy is considered standard of care for adjuvant peri-operative treatment of many spinal tumors, including those with instrumented fusion. Unfortunately, radiation treatment has been linked to increased risk of pseudoarthrosis. Newer focused radiotherapy strategies with enhanced conformality could offer improved fusion rates for these patients, but this has not been confirmed.

Methods

We performed a retrospective analysis of patients at three tertiary care academic institutions with primary and secondary spinal malignancies that underwent resection, instrumented fusion, and peri-operative radiotherapy. Two board certified neuro-radiologists used the Lenke fusion score to grade fusion status at 6 and 12-months after surgery. Secondary outcomes included clinical pseudoarthrosis, wound complications, the effect of radiation timing and radiobiological dose delivered, the use of photons versus protons, tumor type, tumor location, and use of autograft on fusion outcomes.

Results

After review of 1252 spinal tumor patients, there were 60 patients with at least 6 months follow-up that were included in our analyses. Twenty-five of these patients received focused radiotherapy, 20 patients received conventional radiotherapy, and 15 patients were treated with protons. There was no significant difference between the groups for covariates such as smoking status, obesity, diabetes, intraoperative use of autograft, and use of peri-operative chemotherapy. There was a significantly higher rate of fusion for patients treated with focused radiotherapy compared to those treated with conventional radiotherapy at 6-months (64.0% versus 30.0%, Odds ratio: 4.15, p = 0.036) and 12-months (80.0% versus 42.1%, OR: 5.50, p = 0.022). There was a significantly higher rate of clinical pseudoarthrosis in the conventional radiotherapy cohort compared to patients in the focused radiotherapy cohort (19.1% versus 0%, p = 0.037). There was no difference in fusion outcomes for any of the secondary outcomes except for use of autograft. The use of intra-operative autograft was associated with an improved fusion at 12-months (66.7% versus 37.5%, OR: 3.33, p = 0.043).

Conclusion

Focused radiotherapy may be associated with an improved rate of fusion and clinical pseudoarthrosis when compared to conventional radiation delivery strategies in patients with spinal tumors. Use of autograft at the time of surgery may be associated with improved 12-month fusion rates. Further large-scale prospective and randomized controlled studies are needed to better stratify the effects of radiation delivery modality in these patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The datasets generated during and/or analyzed during the current study are not publicly available due to institutional policies for electronic medical record data but are available from the corresponding author on reasonable request.

References

  1. Miften M, Olch A, Mihailidis D, Moran J, Pawlicki T, Molineu A, Li H, Wijesooriya K, Shi J, Xia P, Papanikolaou N, Low DA (2018) Tolerance limits and methodologies for IMRT measurement-based verification QA: Recommendations of AAPM Task Group No. 218. Med Phys 45:e53–e83. https://doi.org/10.1002/mp.12810

    Article  PubMed  Google Scholar 

  2. Ma L, Wang L, Tseng CL, Sahgal A (2017) Emerging technologies in stereotactic body radiotherapy. Chin Clin Oncol 6:S12. https://doi.org/10.21037/cco.2017.06.19

    Article  PubMed  Google Scholar 

  3. Martin AG, Thomas SJ, Harden SV, Burnet NG (2015) Evaluating competing and emerging technologies for stereotactic body radiotherapy and other advanced radiotherapy techniques. Clin Oncol (R Coll Radiol) 27:251–259. https://doi.org/10.1016/j.clon.2015.01.034

    Article  CAS  Google Scholar 

  4. Zeng KL, Tseng CL, Soliman H, Weiss Y, Sahgal A, Myrehaug S (2019) Stereotactic Body Radiotherapy (SBRT) for oligometastatic spine metastases: an overview. Front Oncol 9:337. https://doi.org/10.3389/fonc.2019.00337

    Article  PubMed  PubMed Central  Google Scholar 

  5. Redmond KJ, Robertson S, Lo SS, Soltys SG, Ryu S, McNutt T, Chao ST, Yamada Y, Ghia A, Chang EL, Sheehan J, Sahgal A (2017) Consensus contouring guidelines for postoperative stereotactic body radiation therapy for metastatic solid tumor malignancies to the spine. Int J Radiat Oncol Biol Phys 97:64–74. https://doi.org/10.1016/j.ijrobp.2016.09.014

    Article  PubMed  Google Scholar 

  6. Redmond KJ, Sciubba D, Khan M, Gui C, Lo SL, Gokaslan ZL, Leaf B, Kleinberg L, Grimm J, Ye X, Lim M (2020) A Phase 2 study of post-operative stereotactic body radiation therapy (SBRT) for solid tumor spine Metastases. Int J Radiat Oncol Biol Phys 106:261–268. https://doi.org/10.1016/j.ijrobp.2019.10.011

    Article  CAS  PubMed  Google Scholar 

  7. Longo M, De la Garza RR, Gelfand Y, Echt M, Kinon MD, Yassari R (2019) Incidence and predictors of hardware failure after instrumentation for spine metastasis: a single-institutional series. World Neurosurg 125:e1170–e1175. https://doi.org/10.1016/j.wneu.2019.01.272

    Article  PubMed  Google Scholar 

  8. Gouk SS, Lim TM, Teoh SH, Sun WQ (2008) Alterations of human acellular tissue matrix by gamma irradiation: histology, biomechanical property, stability, in vitro cell repopulation, and remodeling. J Biomed Mater Res B Appl Biomater 84:205–217. https://doi.org/10.1002/jbm.b.30862

    Article  CAS  PubMed  Google Scholar 

  9. She C, Shi GL, Xu W, Zhou XZ, Li J, Tian Y, Li J, Li WH, Dong QR, Ren PG (2016) Effect of low-dose X-ray irradiation and Ti particles on the osseointegration of prosthetic. J Orthop Res 34:1688–1696. https://doi.org/10.1002/jor.23179

    Article  CAS  PubMed  Google Scholar 

  10. Chen M, Huang Q, Xu W, She C, Xie ZG, Mao YT, Dong QR, Ling M (2014) Low-dose X-ray irradiation promotes osteoblast proliferation, differentiation and fracture healing. PLoS ONE 9:e104016. https://doi.org/10.1371/journal.pone.0104016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Song XS, Zhou XZ, Zhang G, Dong QR, Qin L (2010) Low-dose X-ray irradiation promotes fracture healing through up-regulation of vascular endothelial growth factor. Med Hypotheses 75:522–524. https://doi.org/10.1016/j.mehy.2010.07.012

    Article  CAS  PubMed  Google Scholar 

  12. Itshayek E, Cohen JE, Yamada Y, Gokaslan Z, Polly DW, Rhines LD, Schmidt MH, Varga PP, Mahgarefteh S, Fraifeld S, Gerszten PC, Fisher CG (2014) Timing of stereotactic radiosurgery and surgery and wound healing in patients with spinal tumors: a systematic review and expert opinions. Neurol Res 36:510–523. https://doi.org/10.1179/1743132814Y.0000000380

    Article  PubMed  Google Scholar 

  13. Akinduro OO, Garcia DP, Domingo RA, Vivas-Buitrago T, Sousa-Pinto B, Bydon M, Clarke MJ, Gokaslan ZL, Kalani MA, Abode-Iyamah K, Quinones-Hinojosa A (2021) Cervical chordomas: multicenter case series and meta-analysis. J Neurooncol 153:65–77. https://doi.org/10.1007/s11060-021-03742-6

    Article  PubMed  Google Scholar 

  14. Akinduro OO, Suarez-Meade P, Garcia D, Brown DA, Sarabia-Estrada R, Attia S, Gokaslan ZL, Quinones-Hinojosa A (2021) Targeted therapy for chordoma: key molecular signaling pathways and the role of multimodal therapy. Target Oncol 16:325–337. https://doi.org/10.1007/s11523-021-00814-5

    Article  PubMed  Google Scholar 

  15. Bydon M, De la Garza-Ramos R, Abt NB, Gokaslan ZL, Wolinsky JP, Sciubba DM, Bydon A, Witham TF (2014) Impact of smoking on complication and pseudarthrosis rates after single- and 2-level posterolateral fusion of the lumbar spine. Spine (Phila Pa 1976) 39:1765–1770. https://doi.org/10.1097/BRS.0000000000000527

    Article  Google Scholar 

  16. Watkins MB (1964) Posterolateral fusion in pseudarthrosis and posterior element defects of the lumbosacral spine. Clin Orthop Relat Res 35:80–85

    CAS  PubMed  Google Scholar 

  17. Zhang M, Appelboom G, Ratliff JK, Soltys SG, Adler JR Jr, Park J, Chang SD (2018) Radiographic rate and clinical impact of pseudarthrosis in spine radiosurgery for metastatic spinal disease. Cureus 10:e3631. https://doi.org/10.7759/cureus.3631

    Article  PubMed  PubMed Central  Google Scholar 

  18. Sahgal A, Roberge D, Schellenberg D, Purdie TG, Swaminath A, Pantarotto J, Filion E, Gabos Z, Butler J, Letourneau D, Masucci GL, Mulroy L, Bezjak A, Dawson LA, Parliament M, Association TC (2012) The Canadian association of radiation oncology scope of practice guidelines for lung, liver and spine stereotactic body radiotherapy. Clin Oncol (R Coll Radiol) 24:629–639. https://doi.org/10.1016/j.clon.2012.04.006

    Article  CAS  Google Scholar 

  19. Chang JH, Shin JH, Yamada YJ, Mesfin A, Fehlings MG, Rhines LD, Sahgal A (2016) Stereotactic body radiotherapy for spinal metastases: what are the risks and how do we minimize them? (Spine Phila Pa 1976) 41(Suppl 20):S238–S245. https://doi.org/10.1097/BRS.0000000000001823

    Article  Google Scholar 

  20. Hartsell WF, Scott CB, Bruner DW, Scarantino CW, Ivker RA, Roach M 3rd, Suh JH, Demas WF, Movsas B, Petersen IA, Konski AA, Cleeland CS, Janjan NA, DeSilvio M (2005) Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases. J Natl Cancer Inst 97:798–804. https://doi.org/10.1093/jnci/dji139

    Article  PubMed  Google Scholar 

  21. Indelicato DJ, Rotondo RL, Begosh-Mayne D, Scarborough MT, Gibbs CP, Morris CG, Mendenhall WM (2016) A prospective outcomes study of proton therapy for chordomas and chondrosarcomas of the spine. Int J Radiat Oncol Biol Phys 95:297–303. https://doi.org/10.1016/j.ijrobp.2016.01.057

    Article  PubMed  Google Scholar 

  22. Lenke LG, Bridwell KH, Bullis D, Betz RR, Baldus C, Schoenecker PL (1992) Results of in situ fusion for isthmic spondylolisthesis. J Spinal Disord 5:433–442. https://doi.org/10.1097/00002517-199212000-00008

    Article  CAS  PubMed  Google Scholar 

  23. Harel R, Chao S, Krishnaney A, Emch T, Benzel EC, Angelov L (2010) Spine instrumentation failure after spine tumor resection and radiation: comparing conventional radiotherapy with stereotactic radiosurgery outcomes. World Neurosurg 74:517–522. https://doi.org/10.1016/j.wneu.2010.06.037

    Article  PubMed  Google Scholar 

  24. Kim TK, Cho W, Youn SM, Chang UK (2016) The effect of perioperative radiation therapy on spinal bone fusion following spine tumor surgery. J Korean Neurosurg Soc 59:597–603. https://doi.org/10.3340/jkns.2016.59.6.597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Cox BW, Spratt DE, Lovelock M, Bilsky MH, Lis E, Ryu S, Sheehan J, Gerszten PC, Chang E, Gibbs I, Soltys S, Sahgal A, Deasy J, Flickinger J, Quader M, Mindea S, Yamada Y (2012) International Spine radiosurgery consortium consensus guidelines for target volume definition in spinal stereotactic radiosurgery. Int J Radiat Oncol Biol Phys 83:e597-605. https://doi.org/10.1016/j.ijrobp.2012.03.009

    Article  PubMed  Google Scholar 

  26. Redmond KJ, Lo SS, Soltys SG, Yamada Y, Barani IJ, Brown PD, Chang EL, Gerszten PC, Chao ST, Amdur RJ, De Salles AA, Guckenberger M, Teh BS, Sheehan J, Kersh CR, Fehlings MG, Sohn MJ, Chang UK, Ryu S, Gibbs IC, Sahgal A (2017) Consensus guidelines for postoperative stereotactic body radiation therapy for spinal metastases: results of an international survey. J Neurosurg Spine 26:299–306. https://doi.org/10.3171/2016.8.SPINE16121

    Article  PubMed  Google Scholar 

  27. Amankulor NM, Xu R, Iorgulescu JB, Chapman T, Reiner AS, Riedel E, Lis E, Yamada Y, Bilsky M, Laufer I (2014) The incidence and patterns of hardware failure after separation surgery in patients with spinal metastatic tumors. Spine J 14:1850–1859. https://doi.org/10.1016/j.spinee.2013.10.028

    Article  PubMed  Google Scholar 

  28. Emery SE, Hughes SS, Junglas WA, Herrington SJ, Pathria MN (1994) The fate of anterior vertebral bone grafts in patients irradiated for neoplasm. Clin Orthop Relat Res. https://doi.org/10.1097/00003086-199403000-00028

    Article  PubMed  Google Scholar 

  29. Dede O, Thuillier D, Pekmezci M, Ames CP, Hu SS, Berven SH, Deviren V (2015) Revision surgery for lumbar pseudarthrosis. Spine J 15:977–982. https://doi.org/10.1016/j.spinee.2013.05.039

    Article  PubMed  Google Scholar 

  30. Kim YJ, Bridwell KH, Lenke LG, Rinella AS, Edwards C (1976) 2nd (2005) Pseudarthrosis in primary fusions for adult idiopathic scoliosis: incidence, risk factors, and outcome analysis. Spine (Phila Pa 1976) 30:468–474. https://doi.org/10.1097/01.brs.0000153392.74639.ea

    Article  Google Scholar 

  31. Cheng JY, Liu CM, Wang YM, Hsu HC, Huang EY, Huang TT, Lee CH, Hung SP, Huang BS (2020) Proton versus photon radiotherapy for primary hepatocellular carcinoma: a propensity-matched analysis. Radiat Oncol 15:159. https://doi.org/10.1186/s13014-020-01605-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Carbonara R, Di Rito A, Monti A, Rubini G, Sardaro A (2019) Proton versus photon radiotherapy for pediatric central nervous system malignancies: a systematic review and meta-analysis of dosimetric comparison studies. J Oncol 2019:5879723. https://doi.org/10.1155/2019/5879723

    Article  PubMed  PubMed Central  Google Scholar 

  33. Zietman AL, Bae K, Slater JD, Shipley WU, Efstathiou JA, Coen JJ, Bush DA, Lunt M, Spiegel DY, Skowronski R, Jabola BR, Rossi CJ (2010) Randomized trial comparing conventional-dose with high-dose conformal radiation therapy in early-stage adenocarcinoma of the prostate: long-term results from proton radiation oncology group/american college of radiology 95–09. J Clin Oncol 28:1106–1111. https://doi.org/10.1200/JCO.2009.25.8475

    Article  PubMed  PubMed Central  Google Scholar 

  34. Delawi D, Dhert WJ, Rillardon L, Gay E, Prestamburgo D, Garcia-Fernandez C, Guerado E, Specchia N, Van Susante JL, Verschoor N, van Ufford HM, Oner FC (2010) A prospective, randomized, controlled, multicenter study of osteogenic protein-1 in instrumented posterolateral fusions: report on safety and feasibility. Spine (Phila Pa 1976) 35:1185–1191. https://doi.org/10.1097/BRS.0b013e3181d3cf28

    Article  CAS  Google Scholar 

  35. Devine JG, Dettori JR, France JC, Brodt E, McGuire RA (2012) The use of rhBMP in spine surgery: is there a cancer risk? Evid Based Spine Care J 3:35–41. https://doi.org/10.1055/s-0031-1298616

    Article  PubMed  PubMed Central  Google Scholar 

  36. Vaccaro AR, Whang PG, Patel T, Phillips FM, Anderson DG, Albert TJ, Hilibrand AS, Brower RS, Kurd MF, Appannagari A, Patel M, Fischgrund JS (2008) The safety and efficacy of OP-1 (rhBMP-7) as a replacement for iliac crest autograft for posterolateral lumbar arthrodesis: minimum 4-year follow-up of a pilot study. Spine J 8:457–465. https://doi.org/10.1016/j.spinee.2007.03.012

    Article  PubMed  Google Scholar 

  37. Orief T, Ramadan I, Seddik Z, Kamal M, Rahmany M, Takayasu M (2010) Comparative evaluation of bone-filled Polymethylmethacrylate implant, autograft fusion, and Polyetheretherketone cervical cage fusion for the treatment of single -level cervical disc disease. Asian J Neurosurg 5:46–56

    PubMed  PubMed Central  Google Scholar 

  38. Barlocher CB, Barth A, Krauss JK, Binggeli R, Seiler RW (2002) Comparative evaluation of microdiscectomy only, autograft fusion, polymethylmethacrylate interposition, and threaded titanium cage fusion for treatment of single-level cervical disc disease: a prospective randomized study in 125 patients. Neurosurg Focus 12:E4. https://doi.org/10.3171/foc.2002.12.1.5

    Article  PubMed  Google Scholar 

  39. Buser Z, Brodke DS, Youssef JA, Meisel HJ, Myhre SL, Hashimoto R, Park JB, Tim Yoon S, Wang JC (2016) Synthetic bone graft versus autograft or allograft for spinal fusion: a systematic review. J Neurosurg Spine 25:509–516. https://doi.org/10.3171/2016.1.SPINE151005

    Article  PubMed  Google Scholar 

  40. Hsu CJ, Chou WY, Teng HP, Chang WN, Chou YJ (2005) Coralline hydroxyapatite and laminectomy-derived bone as adjuvant graft material for lumbar posterolateral fusion. J Neurosurg Spine 3:271–275. https://doi.org/10.3171/spi.2005.3.4.0271

    Article  PubMed  Google Scholar 

  41. Kunakornsawat S, Kirinpanu A, Piyaskulkaew C, Sathira-Angkura V (2013) A comparative study of radiographic results using HEALOS collagen-hydroxyapatite sponge with bone marrow aspiration versus local bone graft in the same patients undergoing posterolateral lumbar fusion. J Med Assoc Thai 96:929–935

    PubMed  Google Scholar 

  42. Park SH, Keller ET, Shiozawa Y (2018) Bone marrow microenvironment as a regulator and therapeutic target for prostate cancer bone metastasis. Calcif Tissue Int 102:152–162. https://doi.org/10.1007/s00223-017-0350-8

    Article  CAS  PubMed  Google Scholar 

  43. Eltoukhy HS, Sinha G, Moore CA, Gergues M, Rameshwar P (2018) Secretome within the bone marrow microenvironment: A basis for mesenchymal stem cell treatment and role in cancer dormancy. Biochimie 155:92–103. https://doi.org/10.1016/j.biochi.2018.05.018

    Article  CAS  PubMed  Google Scholar 

  44. Bergstrom SH, Rudolfsson SH, Bergh A (2016) Rat prostate tumor cells progress in the bone microenvironment to a highly aggressive phenotype. Neoplasia 18:152–161. https://doi.org/10.1016/j.neo.2016.01.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414:105–111. https://doi.org/10.1038/35102167

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

O.O.A. is supported by Neurosurgery Research and Education Foundation Funding, but this funding is not directly related to this project.

Author information

Authors and Affiliations

Authors

Contributions

OOA: writing manuscript, data collection, statistical analysis, reviewed final, GD: writing manuscript, data collection, statistical analysis AG: data collection, JM: data collection, SS: data collection, critically revised manuscript, RK: figure preparation, critically revised manuscript, DT: critically revised manuscript, JS: critically revised manuscript, KM: critically revised manuscript, SV: critically revised manuscript, DB: data collection, MC: critically revised manuscript, MB: critically revised manuscript, JM: critically revised manuscript, MK: critically revised manuscript, AQ: critically revised manuscript, KA: critically revised manuscript, study supervision.

Corresponding author

Correspondence to Oluwaseun O. Akinduro.

Ethics declarations

Conflict of interest

All authors report they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. IRB approval was obtained for this study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Akinduro, O.O., De Biase, G., Goyal, A. et al. Focused versus conventional radiotherapy in spinal oncology: is there any difference in fusion rates and pseudoarthrosis?. J Neurooncol 156, 329–339 (2022). https://doi.org/10.1007/s11060-021-03915-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-021-03915-3

Keywords

Navigation