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Published in: Radiation Oncology 1/2018

Open Access 01-12-2018 | Research

Bone density and pain response following intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy for vertebral metastases - secondary results of a randomized trial

Authors: Tanja Sprave, Vivek Verma, Robert Förster, Ingmar Schlampp, Katharina Hees, Thomas Bruckner, Tilman Bostel, Rami Ateyah El Shafie, Thomas Welzel, Nils Henrik Nicolay, Jürgen Debus, Harald Rief

Published in: Radiation Oncology | Issue 1/2018

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Abstract

Background

This was a prespecified secondary analysis of a randomized trial that analyzed bone density and pain response following fractionated intensity-modulated radiotherapy (IMRT) versus three-dimensional conformal radiotherapy (3DCRT) for palliative management of spinal metastases.

Methods/materials

Sixty patients were enrolled in the single-institutional randomized exploratory trial, randomly assigned to receive IMRT or 3DCRT (30 Gy in 10 fractions). Along with pain response (measured by the Visual Analog Scale (VAS) and Chow criteria), quantitative bone density was evaluated at baseline, 3, and 6 months in both irradiated and unirradiated spinal bodies, along with rates of pathologic fractures and vertebral compression fractures.

Results

Relative to baseline, bone density increased at 3 and 6 months following IMRT by a median of 24.8% and 33.8%, respectively (p < 0.01 and p = 0.048). These figures in the 3DCRT cohort were 18.5% and 48.4%, respectively (p < 0.01 for both). There were no statistical differences in bone density between IMRT and 3DCRT at 3 (p = 0.723) or 6 months (p = 0.341). Subgroup analysis of osteolytic and osteoblastic metastases showed no differences between groups; however, mixed metastases showed an increase in bone density over baseline in the IMRT (but not 3DCRT) arm. The 3-month rate of the pathological fractures was 15.0% in the IMRT arm vs. 10.5% in the 3DCRT arm. There were no differences in pathological fractures at 3 (p = 0.676) and 6 (p = 1.000) months. The IMRT arm showed improved VAS scores at 3 (p = 0.037) but not 6 months (p = 0.430). Using Chow criteria, pain response was similar at both 3 (p = 0.395) and 6 (p = 0.732) months.

Conclusions

This the first prospective investigation evaluating the impact of IMRT vs. 3DCRT on bone density. Along with pain response and pathologic fracture rates, significant rises in bone density after 3 and 6 months were similar in both cohorts. Future randomized investigations with larger sample sizes are recommended.

Trial registration

NCT, NCT02832830. Registered 14 July 2016
Literature
1.
go back to reference Wong DA, Fornasier VL, MacNab I. Spinal metastases: the obvious, the occult, and the impostors. Spine. 1990;15(1):1–4.CrossRef Wong DA, Fornasier VL, MacNab I. Spinal metastases: the obvious, the occult, and the impostors. Spine. 1990;15(1):1–4.CrossRef
2.
go back to reference Sze WM, Shelley M, Held I, Mason M. Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy - a systematic review of the randomised trials. Cochrane Database Syst Rev. 2004;2:CD004721. Sze WM, Shelley M, Held I, Mason M. Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy - a systematic review of the randomised trials. Cochrane Database Syst Rev. 2004;2:CD004721.
3.
go back to reference McQuay HJ, Collins SL, Carroll D, Moore RA. Radiotherapy for the palliation of painful bone metastases. Cochrane Database Syst Rev. 2000;2:Cd001793. McQuay HJ, Collins SL, Carroll D, Moore RA. Radiotherapy for the palliation of painful bone metastases. Cochrane Database Syst Rev. 2000;2:Cd001793.
4.
go back to reference Meyerhof E, Sprave T, Welte SE, Nicolay NH, Forster R, Bostel T, Bruckner T, Schlampp I, Debus J, Rief H. Radiation-induced toxicity after image-guided and intensity-modulated radiotherapy versus external beam radiotherapy for patients with spinal bone metastases (IRON-1): a study protocol for a randomized controlled pilot trial. Trials. 2017;18(1):98.CrossRef Meyerhof E, Sprave T, Welte SE, Nicolay NH, Forster R, Bostel T, Bruckner T, Schlampp I, Debus J, Rief H. Radiation-induced toxicity after image-guided and intensity-modulated radiotherapy versus external beam radiotherapy for patients with spinal bone metastases (IRON-1): a study protocol for a randomized controlled pilot trial. Trials. 2017;18(1):98.CrossRef
5.
go back to reference Chow E, Wu JS, Hoskin P, Coia LR, Bentzen SM, Blitzer PH. International consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases. Radiother Oncol. 2002;64(3):275–80.CrossRef Chow E, Wu JS, Hoskin P, Coia LR, Bentzen SM, Blitzer PH. International consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases. Radiother Oncol. 2002;64(3):275–80.CrossRef
6.
go back to reference Marks LB, Yorke ED, Jackson A, Ten Haken RK, Constine LS, Eisbruch A, Bentzen SM, Nam J, Deasy JO. Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S10–9.CrossRef Marks LB, Yorke ED, Jackson A, Ten Haken RK, Constine LS, Eisbruch A, Bentzen SM, Nam J, Deasy JO. Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S10–9.CrossRef
7.
go back to reference Sprave T, Verma V, Forster R, Schlampp I, Bruckner T, Bostel T, Welte SE, Tonndorf-Martini E, El Shafie R, Nicolay NH, et al. Radiation-induced acute toxicities after image-guided intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy for patients with spinal metastases (IRON-1 trial) : First results of a randomized controlled trial. Strahlentherapie und Onkologie. 2018. https://doi.org/10.1007/s00066-018-1333-z Epub ahead of print.CrossRef Sprave T, Verma V, Forster R, Schlampp I, Bruckner T, Bostel T, Welte SE, Tonndorf-Martini E, El Shafie R, Nicolay NH, et al. Radiation-induced acute toxicities after image-guided intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy for patients with spinal metastases (IRON-1 trial) : First results of a randomized controlled trial. Strahlentherapie und Onkologie. 2018. https://​doi.​org/​10.​1007/​s00066-018-1333-z Epub ahead of print.CrossRef
8.
go back to reference Sprave T, Welte SE, Bruckner T, Forster R, Bostel T, Schlampp I, Nicolay NH, Debus J, Rief H. Intensity-modulated radiotherapy with integrated-boost in patients with bone metastasis of the spine: study protocol for a randomized controlled trial. Trials. 2018;19(1):59.CrossRef Sprave T, Welte SE, Bruckner T, Forster R, Bostel T, Schlampp I, Nicolay NH, Debus J, Rief H. Intensity-modulated radiotherapy with integrated-boost in patients with bone metastasis of the spine: study protocol for a randomized controlled trial. Trials. 2018;19(1):59.CrossRef
9.
go back to reference Eggermont F, Derikx LC, Verdonschot N, Hannink G, Kaatee R, Tanck E, van der Linden YM. Limited short-term effect of palliative radiation therapy on quantitative computed tomography-derived bone mineral density in femora with metastases. Advances in radiation oncology. 2017;2(1):53–61.CrossRef Eggermont F, Derikx LC, Verdonschot N, Hannink G, Kaatee R, Tanck E, van der Linden YM. Limited short-term effect of palliative radiation therapy on quantitative computed tomography-derived bone mineral density in femora with metastases. Advances in radiation oncology. 2017;2(1):53–61.CrossRef
10.
go back to reference Rieden K, Adolph J, Lellig U, Zum Winkel K. The radiotherapeutic effect on bone metastases in relation to the frequency of metastases, sites of metastases and histology of the primary tumor. Strahlentherapie und Onkologie. 1989;165(5):380–5.PubMed Rieden K, Adolph J, Lellig U, Zum Winkel K. The radiotherapeutic effect on bone metastases in relation to the frequency of metastases, sites of metastases and histology of the primary tumor. Strahlentherapie und Onkologie. 1989;165(5):380–5.PubMed
11.
go back to reference Wachenfeld I, Sanner G, Bottcher HD, Kollath J. The remineralization of the vertebral metastases of breast carcinoma after radiotherapy. Strahlentherapie und Onkologie. 1996;172(6):332–41.PubMed Wachenfeld I, Sanner G, Bottcher HD, Kollath J. The remineralization of the vertebral metastases of breast carcinoma after radiotherapy. Strahlentherapie und Onkologie. 1996;172(6):332–41.PubMed
12.
go back to reference Koswig S, Budach V. Remineralization and pain relief in bone metastases after after different radiotherapy fractions (10 times 3 Gy vs. 1 time 8 Gy). A prospective study. Strahlenther Onkol. 1999;175(10):500–8.CrossRef Koswig S, Budach V. Remineralization and pain relief in bone metastases after after different radiotherapy fractions (10 times 3 Gy vs. 1 time 8 Gy). A prospective study. Strahlenther Onkol. 1999;175(10):500–8.CrossRef
13.
go back to reference Rief H, Omlor G, Akbar M, Welzel T, Bruckner T, Rieken S, Haefner MF, Schlampp I, Gioules A, Habermehl D, et al. Feasibility of isometric spinal muscle training in patients with bone metastases under radiation therapy - first results of a randomized pilot trial. BMC Cancer. 2014;14:67.CrossRef Rief H, Omlor G, Akbar M, Welzel T, Bruckner T, Rieken S, Haefner MF, Schlampp I, Gioules A, Habermehl D, et al. Feasibility of isometric spinal muscle training in patients with bone metastases under radiation therapy - first results of a randomized pilot trial. BMC Cancer. 2014;14:67.CrossRef
14.
go back to reference Strang P, Bergqvist J. Does palliative chemotherapy provide a palliative effect on symptoms in late palliative stages? An interview study with oncologists. Acta oncologica. 2017;56(10):1258–64.CrossRef Strang P, Bergqvist J. Does palliative chemotherapy provide a palliative effect on symptoms in late palliative stages? An interview study with oncologists. Acta oncologica. 2017;56(10):1258–64.CrossRef
15.
go back to reference Daimon T, Kosaka T, Oya M. A metastatic castration resistant prostate cancer patient with multiple bone metastases has durable biochemical and radiological response to docetaxel chemotherapy. American journal of clinical and experimental urology. 2016;4(2):28–31.PubMedPubMedCentral Daimon T, Kosaka T, Oya M. A metastatic castration resistant prostate cancer patient with multiple bone metastases has durable biochemical and radiological response to docetaxel chemotherapy. American journal of clinical and experimental urology. 2016;4(2):28–31.PubMedPubMedCentral
16.
go back to reference Nieder C, Haukland E, Mannsaker B, Norum J. Impact of intense systemic therapy and improved survival on the use of palliative radiotherapy in patients with bone metastases from prostate cancer. Oncol Lett. 2016;12(4):2930–5.CrossRef Nieder C, Haukland E, Mannsaker B, Norum J. Impact of intense systemic therapy and improved survival on the use of palliative radiotherapy in patients with bone metastases from prostate cancer. Oncol Lett. 2016;12(4):2930–5.CrossRef
17.
go back to reference Steinauer K, Huang DJ, Eppenberger-Castori S, Amann E, Guth U. Bone metastases in breast cancer: frequency, metastatic pattern and non-systemic locoregional therapy. Journal of bone oncology. 2014;3(2):54–60.CrossRef Steinauer K, Huang DJ, Eppenberger-Castori S, Amann E, Guth U. Bone metastases in breast cancer: frequency, metastatic pattern and non-systemic locoregional therapy. Journal of bone oncology. 2014;3(2):54–60.CrossRef
18.
go back to reference Groenen KH, Pouw MH, Hannink G, Hosman AJ, van der Linden YM, Verdonschot N, Tanck E. The effect of radiotherapy, and radiotherapy combined with bisphosphonates or RANK ligand inhibitors on bone quality in bone metastases. A systematic review. Radiother Oncol. 2016;119(2):194–201.CrossRef Groenen KH, Pouw MH, Hannink G, Hosman AJ, van der Linden YM, Verdonschot N, Tanck E. The effect of radiotherapy, and radiotherapy combined with bisphosphonates or RANK ligand inhibitors on bone quality in bone metastases. A systematic review. Radiother Oncol. 2016;119(2):194–201.CrossRef
19.
go back to reference Leung HW, Wang SY, Jin-Jhih H, Chan AL. Abscopal effect of radiation on bone metastases of breast cancer: a case report. Cancer Biol. Ther. 2018;19(1):20–4.CrossRef Leung HW, Wang SY, Jin-Jhih H, Chan AL. Abscopal effect of radiation on bone metastases of breast cancer: a case report. Cancer Biol. Ther. 2018;19(1):20–4.CrossRef
20.
go back to reference Brix N, Tiefenthaller A, Anders H, Belka C, Lauber K. Abscopal, immunological effects of radiotherapy: narrowing the gap between clinical and preclinical experiences. Immunol Rev. 2017;280(1):249–79.CrossRef Brix N, Tiefenthaller A, Anders H, Belka C, Lauber K. Abscopal, immunological effects of radiotherapy: narrowing the gap between clinical and preclinical experiences. Immunol Rev. 2017;280(1):249–79.CrossRef
Metadata
Title
Bone density and pain response following intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy for vertebral metastases - secondary results of a randomized trial
Authors
Tanja Sprave
Vivek Verma
Robert Förster
Ingmar Schlampp
Katharina Hees
Thomas Bruckner
Tilman Bostel
Rami Ateyah El Shafie
Thomas Welzel
Nils Henrik Nicolay
Jürgen Debus
Harald Rief
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2018
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-018-1161-4

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