Long-term outcome after combined kyphoplasty and intraoperative radiotherapy (Kypho-IORT) for vertebral tumors

Frederic Bludau, Laura Winter, Grit Welzel, Udo Obertacke, Frank Schneider, Frederik Wenz, Arne Mathias Ruder, Frank A Giordano, Frederic Bludau, Laura Winter, Grit Welzel, Udo Obertacke, Frank Schneider, Frederik Wenz, Arne Mathias Ruder, Frank A Giordano

Abstract

Introduction: The spine represents the site which is most frequently affected by bone metastases in patients with systemic cancer. Of all local treatment options, combined kyphoplasty and intraoperative radiotherapy (Kypho-IORT) provides both, instantaneous stabilization and immediate pain relief. We here report on the long-term outcomes of the largest cohort treated with Kypho-IORT to date.

Methods: Between 2009 and 2019 a total of 104 patients underwent Kypho-IORT to vertebral tumors in the thoracic, lumbar, or sacral spine with transpedicular kyphoplasty and intraoperative irradiation with a needle-shaped electronic brachytherapy source at our center. Patients were treated either on trial, within the prospective Kypho-IORT studies (NCT01280032 and NCT02773966), or, after completion of the study, off trial but compliant with the study protocol. Follow-up and imaging with computed tomography (CT) or magnetic resonance imaging was scheduled after 3 and 6 months and then bi-annually.

Results: A total of 143 vertebrae (89 thoracic spine, 53 lumbar spine, and 1 sacral spine) were treated in 104 patients. The median follow-up was 14.5 months (range 0.4-109). Local progression occurred in 10 patients (10 vertebrae) after a median time of 22.3 months (range 1.5-73) resulting in local control rates of 97.1, 95.9, and 94.2% at 6, 12, and 24 months, respectively. Overall survival was 74.6, 61.7, and 50.3% at 6, 12, and 24 months, respectively. A single serious adverse event was reported.

Conclusion: In addition to immediate pain reduction and stabilization, Kypho-IORT shows excellent long-term local control with minimal side effects.

Keywords: Electronic brachytherapy; Intraoperative radiotherapy; Kypho-IORT; Kyphoplasty; Spine; Vertebral metastases.

Conflict of interest statement

LW, GW, UO, FW and AMR have no competing interests to disclose. FB and FS report grants and personal fees from Carl Zeiss Meditec AG, during the conduct of the study; FG reports grants, personal fees, and patents from or related to Carl Zeiss Meditec AG, grants from Elekta AB; grants and personal fees from NOXXON Pharma AG, personal fees from Bristol-Myers Squibb, personal fees from Roche Pharma AG, personal fees from MSD Sharp and Dohme GmbH, personal fees from AstraZeneca GmbH, non-financial support from Oncare GmbH, outside the submitted work.

Figures

Fig. 1
Fig. 1
Local control after Kypho-IORT. Shown are the Kaplan–Meier plots for 89 vertebrae of the thoracic spine and 53 vertebrae of the lumbar spine as well as a combined plot of thoracic, lumbar, and sacral vertebrae treated with Kypho-IORT at our institution (the single patient with a treatment of 1 vertebra of the sacral spine died after 6 weeks and cannot be displayed as curve in the graph)
Fig. 2
Fig. 2
Overall survival after Kypho-IORT. Displayed is the overall survival of 104 patients as Kaplan–Meier plot

References

    1. Perrin RG, Laxton AW. Metastatic spine disease: epidemiology, pathophysiology, and evaluation of patients. Neurosurg Clin N Am. 2004;15(4):365–373. doi: 10.1016/j.nec.2004.04.018.
    1. Huvos AG. Bone tumors: diagnosis, treatment and prognosis. 2. New York: W.B. Saunders Company and Cbs Educational and Professional Publishing; 1987.
    1. Lutz S, Balboni T, Jones J, Lo S, Petit J, Rich SE, et al. Palliative radiation therapy for bone metastases: update of an ASTRO evidence-based guideline. Pract Radiat Oncol. 2017;7(1):4–12. doi: 10.1016/j.prro.2016.08.001.
    1. Berenson J, Pflugmacher R, Jarzem P, Zonder J, Schechtman K, Tillman JB, et al. Balloon kyphoplasty versus non-surgical fracture management for treatment of painful vertebral body compression fractures in patients with cancer: a multicentre, randomised controlled trial. Lancet Oncol. 2011;12(3):225–235. doi: 10.1016/S1470-2045(11)70008-0.
    1. Prezzano KM, Prasad D, Hermann GM, Belal AN, Alberico RA. Radiofrequency ablation and radiation therapy improve local control in spinal metastases compared to radiofrequency ablation alone. Am J Hosp Palliat Care. 2019;36(5):417–422. doi: 10.1177/1049909118819460.
    1. Khalil DN, Smith EL, Brentjens RJ, Wolchok JD. The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nat Rev Clin Oncol. 2016;13(5):273–290. doi: 10.1038/nrclinonc.2016.25.
    1. Botta L, Dal Maso L, Guzzinati S, Panato C, Gatta G, Trama A, et al. Changes in life expectancy for cancer patients over time since diagnosis. J Adv Res. 2019;20:153–159. doi: 10.1016/j.jare.2019.07.002.
    1. Kokkonen K, Tasmuth T, Lehto JT, Kautiainen H, Elme A, Jääskeläinen A-S, et al. Cancer patients' symptom burden and health-related quality of life (HRQoL) at tertiary cancer center from 2006 to 2013: a cross-sectional study. Anticancer Res. 2019;39(1):271–277. doi: 10.21873/anticanres.13107.
    1. Bludau F, Welzel G, Reis T, Schneider F, Sperk E, Neumaier C, et al. Phase I/II trial of combined kyphoplasty and intraoperative radiotherapy in spinal metastases. Spine J. 2018;18(5):776–781. doi: 10.1016/j.spinee.2017.09.011.
    1. Bludau F, Welzel G, Reis T, Abo-Madyan Y, Sperk E, Schneider F, et al. Combined kyphoplasty and intraoperative radiotherapy (Kypho-IORT) versus external beam radiotherapy (EBRT) for painful vertebral metastases—a randomized phase III study. BMC Cancer. 2019;19(1):430. doi: 10.1186/s12885-019-5666-5.
    1. Koswig S, Budach V. Remineralisation und Schmerzlinderung von Knochenmetastasen nach unterschiedlich fraktionierter Strahlentherapie (10mal 3 Gy vs. 1mal 8 Gy)Eine prospektive Studie. Strahlenther Onkol. 1999;175(10):500–508. doi: 10.1007/s000660050061.
    1. Husain ZA, Sahgal A, De Salles A, Funaro M, Glover J, Hayashi M, et al. Stereotactic body radiotherapy for de novo spinal metastases: systematic review. J Neurosurg Spine. 2017;27(3):295–302. doi: 10.3171/2017.1.SPINE16684.
    1. Palma DA, Olson R, Harrow S, Gaede S, Louie AV, Haasbeek C, et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet. 2019;393(10185):2051–2058. doi: 10.1016/S0140-6736(18)32487-5.
    1. Chang U-K, Cho W-I, Kim M-S, Cho CK, Lee DH, Rhee CH. Local tumor control after retreatment of spinal metastasis using stereotactic body radiotherapy; comparison with initial treatment group. Acta Oncol. 2012;51(5):589–595. doi: 10.3109/0284186X.2012.666637.
    1. Balagamwala EH, Naik M, Reddy CA, Angelov L, Suh JH, Djemil T, et al. Pain flare after stereotactic radiosurgery for spine metastases. J Radiosurg SBRT. 2018;5(2):99–105.
    1. Chiang A, Zeng L, Zhang L, Lochray F, Korol R, Loblaw A, et al. Pain flare is a common adverse event in steroid-naïve patients after spine stereotactic body radiation therapy: a prospective clinical trial. Int J Radiat Oncol Biol Phys. 2013;86(4):638–642. doi: 10.1016/j.ijrobp.2013.03.022.
    1. Mantel F, Sweeney RA, Klement RJ, Hawkins MA, Belderbos J, Ahmed M, et al. Risk factors for vertebral compression fracture after spine stereotactic body radiation therapy: long-term results of a prospective phase 2 study. Radiother Oncol. 2019;141:62–66. doi: 10.1016/j.radonc.2019.08.026.
    1. Rose PS, Laufer I, Boland PJ, Hanover A, Bilsky MH, Yamada J, et al. Risk of fracture after single fraction image-guided intensity-modulated radiation therapy to spinal metastases. J Clin Oncol. 2009;27(30):5075–5079. doi: 10.1200/JCO.2008.19.3508.
    1. Moussazadeh N, Lis E, Katsoulakis E, Kahn S, Svoboda M, DiStefano NM, et al. Five-year outcomes of high-dose single-fraction spinal stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2015;93(2):361–367. doi: 10.1016/j.ijrobp.2015.05.035.
    1. Lockney DT, Hopkins B, Lockney NA, Coleman CZ, Rubin E, Lis E, et al. Adjacent level fracture incidence in single fraction high dose spinal radiosurgery. Ann Transl Med. 2019;7(10):211. doi: 10.21037/atm.2019.04.68.
    1. Pflugmacher R, Schroeder RJ, Klostermann CK. Incidence of adjacent vertebral fractures in patients treated with balloon kyphoplasty: two years' prospective follow-up. Acta Radiol (Stockholm, Sweden: 1987) 2006;47(8):830–840.
    1. Schneider F, Clausen S, Jahnke A, Steil V, Bludau F, Sutterlin M, et al. Radiation protection for an intraoperative X-ray source compared to C-arm fluoroscopy. Z Med Phys. 2014;24(3):243–251. doi: 10.1016/j.zemedi.2013.10.006.
    1. Barzilai O, McLaughlin L, Amato M-K, Reiner AS, Ogilvie SQ, Lis E, et al. Minimal access surgery for spinal metastases: prospective evaluation of a treatment algorithm using patient-reported outcomes. World Neurosurg. 2018;120:e889–e901. doi: 10.1016/j.wneu.2018.08.182.
    1. Barzilai O, Versteeg AL, Sahgal A, Rhines LD, Bilsky MH, Sciubba DM, et al. Survival, local control, and health-related quality of life in patients with oligometastatic and polymetastatic spinal tumors: a multicenter, international study. Cancer. 2019;125(5):770–778. doi: 10.1002/cncr.31870.
    1. Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst. 2002;94(19):1458–1468. doi: 10.1093/jnci/94.19.1458.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel