Response assessment after stereotactic body radiation therapy for spine and non-spine bone metastases: results from a single institutional study

Dora Correia, Barbara Moullet, Jennifer Cullmann, Rafael Heiss, Ekin Ermiş, Daniel M Aebersold, Hossein Hemmatazad, Dora Correia, Barbara Moullet, Jennifer Cullmann, Rafael Heiss, Ekin Ermiş, Daniel M Aebersold, Hossein Hemmatazad

Abstract

Background: The use of stereotactic body radiation therapy (SBRT) for tumor and pain control in patients with bone metastases is increasing. We report response assessment after bone SBRT using radiological changes through time and clinical examination of patients.

Methods: We analyzed retrospectively oligo-metastatic/progressive patients with bony lesions treated with SBRT between 12/2008 and 10/2018, without in-field re-irradiation, in our institution. Radiological data were obtained from imaging modalities used for SBRT planning and follow-up purposes in picture archiving and communication system and assessed by two independent radiologists blind to the time of treatment. Several radiological changes were described. Radiographic response assessment was classified according to University of Texas MD Anderson Cancer Center criteria. Pain response and the neurological deficit were captured before and at least 6 months after SBRT.

Results: A total of 35 of the 74 reviewed patients were eligible, presenting 43 bone metastases, with 51.2% (n = 22) located in the vertebral column. Median age at the time of SBRT was 66 years (range 38-84) and 77.1% (n = 27) were male. Histology was mainly prostate (51.4%, n = 18) and breast cancer (14.3%, n = 5). Median total radiation dose delivered was 24 Gy (range 24-42), in three fractions (range 2-7), prescribed to 70-90% isodose-line. After a median follow-up of 1.8 years (range < 1-8.2) for survivors, complete or partial response, stable, and progressive disease occurred in 0%, 11.4% (n = 4), 68.6% (n = 24), and 20.0% (n = 7) of the patients, respectively. Twenty patients (57.1%) died during the follow-up time, all from disease progression, yet 70% (n = 14) from this population with local stable disease after SBRT. From patients who were symptomatic and available for follow-up, almost half (44.4%) reported pain reduction after SBRT.

Conclusions: Eighty percent of the patients showed local control after SBRT for bone metastases. Pain response was favorable. For more accurate response assessment, comparing current imaging modalities with advanced imaging techniques such as functional MRI and PET/CT, in a prospective and standardized way is warranted. Trial registration Retrospectively registered.

Keywords: Pain response; Response assessment; SBRT; Spine metastases.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Study cohort flow diagram. Mets, bone metastases; VMAT, volumetric modulated arc therapy
Fig. 2
Fig. 2
Quantitative parameters evolution and interaction with the imaging method. Abbreviations: SBRT, radiotherapy; CT w/ contrast, computed tomography contrast enhanced; MRI, magnetic resonance imaging; PET/CT, positron emission tomography/ computed tomography; CT-DN, computed tomography density native in Hounsfield units
Fig. 3
Fig. 3
Example of radiological changes of a spine metastasis (A2) treated with SBRT (stable disease (C), yet initially classified as “pseudoprogression” (B)), and associated SBRT-plan (A1)

References

    1. Coleman RE. Metastatic bone disease: Clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. 2001;27(3):165–176. doi: 10.1053/CTRV.2000.0210.
    1. Cecchini MG, Wetterwald A, van der Pluijm G, Thalmann GN. Molecular and biological mechanisms of bone metastasis. EAU Updat Ser. 2005;3(4):214–226. doi: 10.1016/j.euus.2005.09.006.
    1. Maccauro G, Spinelli MS, Mauro S, Perisano C, Graci C, Rosa MA. Physiopathology of Spine Metastasis. Int J Surg Oncol. 2011;2011:1–8. doi: 10.1155/2011/107969.
    1. Galgano M, Fridley J, Oyelese A, et al. Surgical management of spinal metastases. Expert Rev Anticancer Ther . 2018 doi: 10.1080/14737140.2018.1453359.
    1. Lutz S, Berk L, Chang E, et al. Palliative radiotherapy for bone metastases: An ASTRO evidence-based guideline. Int J Radiat Oncol Biol Phys. 2011 doi: 10.1016/j.ijrobp.2010.11.026.
    1. Steenland E, Leer J, Van Houwelingen H, et al. The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study. Radiother Oncol. 1999;52(2):101–109. doi: 10.1016/S0167-8140(99)00110-3.
    1. Yarnold JR. 8 Gy single fraction radiotherapy for the treatment of metastatic skeletal pain: randomised comparison with a multifraction schedule over 12 months of patient follow-up On behalf of the Bone Pain Trial Working Party. Radiother Oncol. 1999;52(2):111–121. doi: 10.1016/S0167-8140(99)00097-3.
    1. Ratanatharathorn V, Powers WE, Moss WT, Perez CA. Bone metastasis: review and critical analysis of random allocation trials of local field treatment. Int J Radiat Oncol. 1999;44(1):1–18. doi: 10.1016/S0360-3016(98)00510-0.
    1. Vellayappan BA, Chao ST, Foote M, et al. The evolution and rise of stereotactic body radiotherapy (SBRT) for spinal metastases. Expert Rev Anticancer Ther. 2018 doi: 10.1080/14737140.2018.1493381.
    1. Ryu S, Deshmukh S, Timmerman RD, et al. Radiosurgery compared to external beam radiotherapy for localized spine metastasis: phase III results of NRG Oncology/RTOG 0631. Int J Radiat Oncol. 2019;105(1):S2–S3. doi: 10.1016/j.ijrobp.2019.06.382.
    1. Sahgal A, Myrehaug SD, Siva S, et al. Stereotactic body radiotherapy versus conventional external beam radiotherapy in patients with painful spinal metastases: an open-label, multicentre, randomised, controlled, phase 2/3 trial. Lancet Oncol. 2021;22(7):1023–1033. doi: 10.1016/S1470-2045(21)00196-0.
    1. Sprave T, Verma V, Förster R, et al. Randomized phase II trial evaluating pain response in patients with spinal metastases following stereotactic body radiotherapy versus three-dimensional conformal radiotherapy. Radiother Oncol. 2018;128(2):274–282. doi: 10.1016/j.radonc.2018.04.030.
    1. Thibault I, Chang EL, Sheehan J, et al. Response assessment after stereotactic body radiotherapy for spinal metastasis: A report from the SPIne response assessment in Neuro-Oncology (SPINO) group. Lancet Oncol. 2015;16(16):e595–e603. doi: 10.1016/S1470-2045(15)00166-7.
    1. Soliman M, Taunk NK, Simons RE, et al. Anatomic and functional imaging in the diagnosis of spine metastases and response assessment after spine radiosurgery. Neurosurg Focus. 2017;42(1):E5. doi: 10.3171/2016.9.FOCUS16350.
    1. Wong E, Howard P, Chan AKM, Atenafu EG, Lu H, Tyrrell P. The initial step towards establishing a quantitative, magnetic resonance imaging-based framework for response assessment of spinal metastases after stereotactic body radiation therapy. Neurosurgery. 2021 doi: 10.1093/neuros/nyab310.
    1. O’Sullivan S, McDermott R, Keys M, O’Sullivan M, Armstrong J, Faul C. Imaging response assessment following stereotactic body radiotherapy for solid tumour metastases of the spine: current challenges and future directions. J Med Imaging Radiat Oncol. 2020;64(3):385–397. doi: 10.1111/1754-9485.13032.
    1. Hwang YJ, Sohn MJ, Lee BH, et al. Radiosurgery for metastatic spinal tumors: follow-up MR findings. Am J Neuroradiol. 2012;33(2):382–387. doi: 10.3174/ajnr.A2760.
    1. Cox BW, Spratt DE, Lovelock M, et al. International spine radiosurgery consortium consensus guidelines for target volume definition in spinal stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2012;83(5):e597–e605. doi: 10.1016/j.ijrobp.2012.03.009.
    1. Costelloe CM, Chuang HH, Madewell JE, Ueno NT. Cancer response criteria and bone metastases: RECIST 1.1, MDA and PERCIST. J Cancer. 2010 doi: 10.7150/jca.1.80.
    1. Cohen J. Statistical power analysis for the behavioral sciences. Routledge; 2013.
    1. Cao Y, Chen H, Sahgal A, et al. An international pooled analysis of SBRT outcomes to oligometastatic spine and non-spine bone metastases. Radiother Oncol . 2021 doi: 10.1016/j.radonc.2021.08.011.
    1. Huang Y, Chen JL, Hsu F, et al. Response assessment of stereotactic body radiation therapy using dynamic contrast-enhanced integrated MR-PET in non-small cell lung cancer patients. J Magn Reson Imaging. 2017;47:191–199. doi: 10.1002/jmri.25758.
    1. Yip C, Cook GJR, Owczarczyk K, Goh V. Challenges in imaging assessment following liver stereotactic body radiotherapy : pitfalls to avoid in clinical practice. Chin Clin Oncol. 2017;6(Suppl 2):1–9. doi: 10.21037/cco.2017.06.06.
    1. Sawlani V, Davies N, Patel M, et al. Evaluation of response to stereotactic radiosurgery in brain metastases using multiparametric magnetic resonance imaging and a review of the literature. Clin Oncol. 2019;31(1):41–49. doi: 10.1016/j.clon.2018.09.003.
    1. Taylor DR, Weaver JA. Tumor pseudoprogression of spinal metastasis after radiosurgery: a novel concept and case reports. J Neurosurg Spine. 2015;22:534–539. doi: 10.3171/2014.10.SPINE14444.Disclosure.
    1. Amini B, Beaman CB, Madewell JE, et al. Osseous pseudoprogression in vertebral bodies treated with stereotactic radiosurgery: a secondary analysis of prospective phase I/II clinical trials. Am J Neuroradiol. 2016;37(2):387–392. doi: 10.3174/ajnr.A4528.
    1. Sahgal A, Myrehaug SD, Siva S, et al. Articles Stereotactic body radiotherapy versus conventional external beam radiotherapy in patients with painful spinal metastases: an open-label, multicentre, randomised, controlled, phase 2/3 trial. Lancet Oncol. 2021;2045(21):1–11. doi: 10.1016/S1470-2045(21)00196-0.
    1. Pielkenrood BJ, Van Der VJM, Van Der LYM, et al. Pain response after stereotactic body radiation therapy versus conventional radiation therapy in patients with bone metastases—a phase 2 randomized controlled trial within a prospective cohort. Radiat Oncol Biol. 2021;110(2):358–367. doi: 10.1016/j.ijrobp.2020.11.060.
    1. Stutz E, Wartenberg M, Hemmatazad H, Hemmatazad H, Hemmatazad H. Epidural tumor pseudoprogression after spine SBRT: a case report and a mini review of the literature. RAS Oncol Ther. 2021 doi: 10.51520/2766-2586-12.
    1. Rose PS, Laufer I, Boland PJ, et al. Risk of fracture after single fraction image-guided intensity-modulated radiation therapy to spinal metastases. J Clin Oncol. 2009;27(30):6–10. doi: 10.1200/JCO.2008.19.3508.
    1. Sahgal A, Atenafu EG, Chao S, et al. Vertebral compression fracture after spine stereotactic body radiotherapy: a multi-institutional analysis with a focus on radiation dose and the spinal instability neoplastic score. J Clin Oncol. 2017;31(27):3426. doi: 10.1200/JCO.2013.50.1411.
    1. Faruqi S, Whyne C, Alghamdi M, Maralani P. Stereotactic body radiation therapy: a review of the pathophysiology and risk factors. Neurosurgery. 2017 doi: 10.1093/neuros/nyx493.
    1. Jawad MS, Fahim DK, Gerszten PC, et al. Vertebral compression fractures after stereotactic body radiation therapy: a large, multi-institutional, multinational evaluation. J Neurosurg Spine. 2016;24:928–936. doi: 10.3171/2015.10.SPINE141261.928.
    1. Ryu S, Deshmukh S, Timmerman RD, et al. Radiosurgery compared to external beam radiotherapy for localized spine metastasis: phase III results of NRG oncology/RTOG 0631. Radiat Oncol Biol. 2013;105(1):S2–S3. doi: 10.1016/j.ijrobp.2019.06.382.

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