Stereotactic versus conventional radiotherapy for pain reduction and quality of life in spinal metastases: study protocol for a randomized controlled trial

Pètra Braam, Philippe Lambin, Johan Bussink, Pètra Braam, Philippe Lambin, Johan Bussink

Abstract

Background: Painful spinal metastases have been treated with conventional radiotherapy for decades, but one-third of the patients have insufficient pain relief after treatment and one-fifth need retreatment. Stereotactic radiotherapy is a method to increase the dose in the spinal metastases with a potentially longer lasting palliative effect without increasing the side effects of the treatment and thereby is expected to improve the quality of life significantly.

Methods/design: This study is a multicenter prospective randomized clinical trial comparing conventional radiotherapy (1 x 8 Gy) with stereotactic radiotherapy (1 x 20 Gy) for pain reduction and quality of life in patients with painful spinal metastases. A total of 386 patients will be randomized between the two treatment groups. Besides pain measured by the Dutch Brief Pain Inventory, quality of life and cost-effectiveness also will be measured. The primary outcome is pain reduction at 6 weeks after treatment. Secondary outcomes will be the time to pain response, duration of pain relief, health-related quality of life and toxicity, as well as cost-effectiveness.

Discussion: This study investigates whether stereotactic radiotherapy with dose escalation for symptomatic spinal metastases can lead to improved pain reduction as compared to conventional radiotherapy without an increase of treatment-related side effects. These results will contribute to the optimization and individualization of the treatment for the patient.

Trial registration: ClinicalTrials.gov identifier NCT02407795 (March 31, 2015).

References

    1. Zeng L, Chow E, Bedard G, Zhang L, Fairchild A, Vassiliou V, et al. Quality of life after palliative radiation therapy for patients with painful bone metastases: results of an international study validating the EORTC QLQ-BM22. Int J Radiat Oncol Biol Phys. 2012;84:337–42. doi: 10.1016/j.ijrobp.2012.05.028.
    1. Steenland E, Leer JW, van Houwelingen H, Post WJ, van den Hout WB, Kievit J, 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;52:101–9. doi: 10.1016/S0167-8140(99)00110-3.
    1. van der Linden YM, Steenland E, van Houwelingen HC, Post WJ, Oei B, Marijnen CA, et al. Patients with a favourable prognosis are equally palliated with single and multiple fraction radiotherapy: results on survival in the Dutch Bone Metastasis Study. Radiother Oncol. 2006;78:245–53. doi: 10.1016/j.radonc.2006.02.007.
    1. Dennis K, Makhani L, Zeng L, Lam H, Chow E. Single fraction conventional external beam radiation therapy for bone metastases: a systematic review of randomised controlled trials. Radiother Oncol. 2013;106:5–14. doi: 10.1016/j.radonc.2012.12.009.
    1. van der Linden YM, Lok JJ, Steenland E, Martijn H, van Houwelingen H, Marijnen CA, et al. Single fraction radiotherapy is efficacious: a further analysis of the Dutch Bone Metastasis Study controlling for the influence of retreatment. Int J Radiat Oncol Biol Phys. 2004;59:528–37. doi: 10.1016/j.ijrobp.2003.10.006.
    1. Howell DD, James JL, Hartsell WF, Suntharalingam M, Machtay M, Suh JH, et al. Single-fraction radiotherapy versus multifraction radiotherapy for palliation of painful vertebral bone metastases-equivalent efficacy, less toxicity, more convenient: a subset analysis of Radiation Therapy Oncology Group trial 97–14. Cancer. 2013;119:888–96. doi: 10.1002/cncr.27616.
    1. Hartsell WF, Scott CB, Bruner DW, Scarantino CW, Ivker RA, Roach M, 3rd, et al. Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases. J Natl Cancer Inst. 2005;97:798–804. doi: 10.1093/jnci/dji139.
    1. Chawla S, Schell MC, Milano MT. Stereotactic body radiation for the spine: a review. Am J Clin Oncol. 2013;36:630–6. doi: 10.1097/COC.0b013e31822dfd71.
    1. Ahmed KA, Stauder MC, Miller RC, Bauer HJ, Rose PS, Olivier KR, et al. Stereotactic body radiation therapy in spinal metastases. Int J Radiat Oncol Biol Phys. 2012;82:803–9. doi: 10.1016/j.ijrobp.2011.11.036.
    1. Sohn S, Chung CK. The role of stereotactic radiosurgery in metastasis to the spine. J Korean Neurosurg Soc. 2012;51:1–7. doi: 10.3340/jkns.2012.51.1.1.
    1. Yamada Y, Bilsky MH, Lovelock DM, Venkatraman ES, Toner S, Johnson J, et al. High-dose, single-fraction image-guided intensity-modulated radiotherapy for metastatic spinal lesions. Int J Radiat Oncol Biol Phys. 2008;71:484–90. doi: 10.1016/j.ijrobp.2007.11.046.
    1. Sahgal A, Whyne CM, Ma L, Larson DA, Fehings MG. Vertebral compression fracture after stereotactic body radiotherapy for spinal metastases. Lancet Oncol. 2013;14:310–20. doi: 10.1016/S1470-2045(13)70101-3.
    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;27:5075–9. doi: 10.1200/JCO.2008.19.3508.
    1. Fisher CG, DiPaola CP, Ryken TC, Bilsky MH, Shaffrey CI, Berven SH, et al. A novel classification system for spinal instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group. Spine. 2010;35:1221–9. doi: 10.1097/BRS.0b013e3181e16ae2.
    1. Fourney DR, Frangou EM, Ryken TC, DiPaola CP, Shaffrey CI, Berven SH, et al. Spinal instability neoplastic score: an analysis of reliability and validity from the spine oncology study group. J Clin Oncol. 2011;29:3072–7. doi: 10.1200/JCO.2010.34.3897.
    1. Chow E, Hird A, Velikova G, Johnson C, Dewolf L, Bezjak A, et al. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for patients with bone metastases: the EORTC QLQ-BM22. Eur J Cancer. 2009;45:1146–52. doi: 10.1016/j.ejca.2008.11.013.
    1. Chow E, Nguyen J, Zhang L, Tseng LM, Hou MF, Faichild A, et al. International field testing of the reliability and validity of the EORTC QLQ-BM22 module to assess health-related quality of life in patients with bone metastases. Cancer. 2012;118:1457–65. doi: 10.1002/cncr.26410.
    1. Groenvold M, Petersen MA, Aaronson NK, Arraras JI, Blazeby JM, Bottomley A, et al. The development of the EORTC QLQ-C15-PAL: a shortened questionnaire for cancer patients in palliative care. Eur J Cancer. 2006;42:55–64. doi: 10.1016/j.ejca.2005.06.022.
    1. Group EQ. EuroQol--a new facility for the measurement of health-related quality of life. Health Policy. 1990;16:199–208. doi: 10.1016/0168-8510(90)90421-9.
    1. Cox BW, Spratt DE, Lovelock M, Bilsky MH, Lis E, Ryu S, et al. International Spine Radiosurgery Consortium consensus guidelines for target volume definition in spinal stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2012;83:597–605. doi: 10.1016/j.ijrobp.2012.03.009.
    1. Ryu S, Jin JY, Jin R, Rock J, Ajlouni M, Movsas B, et al. Partial volume tolerance of the spinal cord and complications of single-dose radiosurgery. Cancer. 2007;109:628–36. doi: 10.1002/cncr.22442.
    1. Garg AK, Shiu AS, Ynag J, Wang XS, Allen P, Brown BW, et al. Phase 1/2 trial of single-session stereotactic body radiotherapy for previously unirradiated spinal metastases. Cancer. 2012;118:5069–77. doi: 10.1002/cncr.27530.
    1. Heron DE, Rajagopalan MS, Stone B, Burton S, Gerszten PC, Dong X, et al. Single-session and multisession CyberKnife radiosurgery for spine metastases-University of Pittsburgh and Georgetown University experience. J Neurosurg Spine. 2012;17:11–8. doi: 10.3171/2012.4.SPINE11902.
    1. Wang XS, Rhines LD, Shiu AS, Yang JN, Selek U, Gning I, et al. Stereotactic body radiation therapy for management of spinal metastases in patients without spinal cord compression: a phase 1–2 trial. Lancet Oncol. 2012;13:395–402. doi: 10.1016/S1470-2045(11)70384-9.
    1. Gerszten PC, Burton SA, Ozhasoglu C, Welch WC. Radiosurgery for spinal metastases: clinical experience in 500 cases from a single institution. Spine. 2007;32:193–9. doi: 10.1097/01.brs.0000251863.76595.a2.
    1. Gerszten PC, Burton SA, Welch WC, Brufsky AM, Lembersky BC, Ozhasoglu C, et al. Single-fraction radiosurgery for the treatment of spinal breast metastases. Cancer. 2005;104:2244–54. doi: 10.1002/cncr.21467.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner