Stereotactic Radiosurgery in Metastatic Spinal Cord Compression

Neoplasm Metastasis Clinical Trial

— Stereocord  

Official title:

A Randomized Trial of Stereotactic Radiosurgery Versus Decompressive Surgery Followed by Postoperative Radiotherapy in Metastatic Spinal Cord Compression

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02167633
• Other study ID #: H-3-2014-050
• Secondary ID: RH SRS in MESCC
• Status: Terminated
• Phase: N/A
• Start date: July 2014
• Est. completion date: September 2016

Study information

• Verified date: March 2021
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To determine whether stereotactic radiosurgery of metastatic spinal cord compression is equivalent to decompressive surgery followed by external body radiation therapy to maintain ability to walk at 6 weeks.

Description:

Metastatic spinal cord compression (MSCC) is an acute event demanding treatment which otherwise would eventually lead to paraplegia in all patients. This is a serious condition for the individual cancer patient and burdensome for the healthcare system. A surgical intervention plus fractionated radiation therapy (FRT) is currently the standard treatment.

Proposed Solution: If spinal cord dose is respected, local tumor control could be equivalent using stereotactic body radiation therapy (SBRT) with minimal risk in comparison to decompression surgery and postoperative conventional radiotherapy without the additional burden on the patient of performing an invasive surgical procedure.

Clinical Impact:

Patients currently requiring surgery plus radiation therapy will potentially benefit form the proposed method. Patients will potentially benefit from reduced toxicity by avoiding the surgical procedure. In addition, a shorter treatment protocol with only one fraction is beneficial.

Aims:

The investigators' hypothesis is that stereotactic body radiation therapy (SBRT) could be equivalent alternative in the case of patients presenting with metastatic spinal cord compression with minor neurologic deficits.

Specific aims:

1. Determine the feasibility of recruiting patients to be randomized towards SBRT vs. of surgery plus FRT

2. Determine the ability to walk after 6 weeks measured from the starting date of treatment

3. Determine the side-effects and quality of life metrics following both treatment arms

4. Determine the rate of local control following therapy using MRI scan

Project Plan:

The investigators intend to investigate if stereotactic body radiation therapy (SBRT) could be equivalent alternative in the case of patients presenting with metastatic spinal cord compression with minor neurologic deficits

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have histological or cytological confirmed malignancy that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective

• Patients must have localized spine metastasis from first cervical to last lumbar vertebra with evidence of radiological SCC (rSCC) on a diagnostic MRI defined as involvement or compression of either the spinal cord or the cauda equina by an epidural mass lesion or metastatic disease causing impingement, indentation or loss of definition of the thecal sac

• A maximum of two separate sites requiring treatment is allowed with maximum two vertebra pr. site

• Eligible for surgery defined by technical assessment by surgeon whether surgical decompression is possible with proper stabilization of the spine

• No medical co-morbidity contradicting anesthesia

• Patient without former treatment for metastatic spinal cord compression with either decompressive surgery and/or radiation therapy

• Patient with mild to moderate neurologic signs are eligible. These neurological signs include radiculopathy, dermatomal sensory change, and muscle strength of involved extremity 4/5 on MRC scale

• Age =18 years

• ECOG performance status =2

• Life expectancy of greater than 3 months

• The effects of ionizing radiation on the developing human fetus are known to be teratogenic. For this reason women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of radiation therapy administration

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Histology of myeloma or lymphoma

• Patients with any spine metastasis that is not planned to be treated per protocol

• Spine instability due to a compression fracture or impending vertebral compression fracture

• Patients with rapid neurologic decline within 24 hours

• Bony retropulsion causing neurologic abnormality

• Prior radiation to the index spine

• Patients for whom an MRI of the spine is medically contraindicated

• Patients allergic to contrast dye used in MRIs

• Patients who are receiving any other investigational agents

• Patients with more than two known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events

• Patient with any serious neurologic condition other than MSCC that could confound the diagnosis and interpretation of radiation induced myelopathy

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Related Conditions & MeSH terms

• Neoplasm Metastasis
• Spinal Cord Compression

Intervention

Procedure:
• Decompression surgery
Patients will undergo posterior decompression/laminectomy on relevant spinal levels depending on neurological symptoms. If there is a need of spinal stabilization after decompression, patients will undergo posterior instrumentation with pedicle screws and titanium rods. Instrumentation will be done two or three levels above and below each level with metastatic affection.

Radiation:
• Radiosurgery
Patients treated with radiosurgery/SBRT will receive a prescribed dose of 16 Gy in 1 fraction to cover as large a fraction as possible the defined target volume
• Fractionated Radiotherapy
Patients allocated to surgery will receive postoperative radiotherapy commencing between 10 to 21 days after decompressive surgery. Target should include the entire vertebral body and the vertebral arch at the operated level of the vertebral column. Patients receiving postoperative radiotherapy will receive 30 Gy in 10 fractions with 3 Gy pr. fraction. The prescribed dose should cover at least 90 % of the defined target volume.

Drug:
• Glucocorticoids
All patients referred with clinical suspicion of metastatic spinal cord compression will receive high dose glucocorticoids. Dose adjusted to risc of side effects.
• Pantoprazole
All patients receiving high dose glucocorticoids will also be prescribed with pantoprazole 40/daily to prevent gastric ulcers

Locations

Country	Name	City	State
Denmark	Rigshospitalet	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

References & Publications (16)

Boehling NS, Grosshans DR, Allen PK, McAleer MF, Burton AW, Azeem S, Rhines LD, Chang EL. Vertebral compression fracture risk after stereotactic body radiotherapy for spinal metastases. J Neurosurg Spine. 2012 Apr;16(4):379-86. doi: 10.3171/2011.11.SPINE116. Epub 2012 Jan 6. — View Citation

Choi D, Morris S, Crockard A, Albert T, Bunger C, Fehlings M, Harrop J, Kawahara N, Martin JA, Massicotte EM, Mazel C, Oner FC, Peul W, Tomita K, Wang M. Assessment of quality of life after surgery for spinal metastases: position statement of the Global Spine Tumour Study Group. World Neurosurg. 2013 Dec;80(6):e175-9. doi: 10.1016/j.wneu.2013.02.054. Epub 2013 Feb 16. — View Citation

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. International Spine Radiosurgery Consortium consensus guidelines for target volume definition in spinal stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2012 Aug 1;83(5):e597-605. doi: 10.1016/j.ijrobp.2012.03.009. Epub 2012 May 19. — View Citation

Cunha MV, Al-Omair A, Atenafu EG, Masucci GL, Letourneau D, Korol R, Yu E, Howard P, Lochray F, da Costa LB, Fehlings MG, Sahgal A. Vertebral compression fracture (VCF) after spine stereotactic body radiation therapy (SBRT): analysis of predictive factors. Int J Radiat Oncol Biol Phys. 2012 Nov 1;84(3):e343-9. doi: 10.1016/j.ijrobp.2012.04.034. Epub 2012 Jun 1. — View Citation

George R, Jeba J, Ramkumar G, Chacko AG, Leng M, Tharyan P. Interventions for the treatment of metastatic extradural spinal cord compression in adults. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD006716. doi: 10.1002/14651858.CD006716.pub2. Review. Update in: Cochrane Database Syst Rev. 2015;9:CD006716. — View Citation

Gerszten PC, Burton SA, Ozhasoglu C, Welch WC. Radiosurgery for spinal metastases: clinical experience in 500 cases from a single institution. Spine (Phila Pa 1976). 2007 Jan 15;32(2):193-9. — View Citation

Jin R, Rock J, Jin JY, Janakiraman N, Kim JH, Movsas B, Ryu S. Single fraction spine radiosurgery for myeloma epidural spinal cord compression. J Exp Ther Oncol. 2009;8(1):35-41. — View Citation

Kirkpatrick JP, van der Kogel AJ, Schultheiss TE. Radiation dose-volume effects in the spinal cord. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S42-9. doi: 10.1016/j.ijrobp.2009.04.095. Review. — View Citation

Morgen SS, Lund-Andersen C, Larsen CF, Engelholm SA, Dahl B. Prognosis in patients with symptomatic metastatic spinal cord compression: survival in different cancer diagnosis in a cohort of 2321 patients. Spine (Phila Pa 1976). 2013 Jul 15;38(16):1362-7. doi: 10.1097/BRS.0b013e318294835b. — View Citation

Patchell RA, Tibbs PA, Regine WF, Payne R, Saris S, Kryscio RJ, Mohiuddin M, Young B. Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Lancet. 2005 Aug 20-26;366(9486):643-8. — View Citation

Rades D, Huttenlocher S, Dunst J, Bajrovic A, Karstens JH, Rudat V, Schild SE. Matched pair analysis comparing surgery followed by radiotherapy and radiotherapy alone for metastatic spinal cord compression. J Clin Oncol. 2010 Aug 1;28(22):3597-604. doi: 10.1200/JCO.2010.28.5635. Epub 2010 Jul 6. — View Citation

Rock JP, Ryu S, Yin FF, Schreiber F, Abdulhak M. The evolving role of stereotactic radiosurgery and stereotactic radiation therapy for patients with spine tumors. J Neurooncol. 2004 Aug-Sep;69(1-3):319-34. Review. — View Citation

Ryu S, Rock J, Jain R, Lu M, Anderson J, Jin JY, Rosenblum M, Movsas B, Kim JH. Radiosurgical decompression of metastatic epidural compression. Cancer. 2010 May 1;116(9):2250-7. doi: 10.1002/cncr.24993. — View Citation

Sahgal A, Ma L, Gibbs I, Gerszten PC, Ryu S, Soltys S, Weinberg V, Wong S, Chang E, Fowler J, Larson DA. Spinal cord tolerance for stereotactic body radiotherapy. Int J Radiat Oncol Biol Phys. 2010 Jun 1;77(2):548-53. doi: 10.1016/j.ijrobp.2009.05.023. Epub 2009 Sep 16. — View Citation

Timmerman RD. An overview of hypofractionation and introduction to this issue of seminars in radiation oncology. Semin Radiat Oncol. 2008 Oct;18(4):215-22. doi: 10.1016/j.semradonc.2008.04.001. — View Citation

Tokuhashi Y, Matsuzaki H, Oda H, Oshima M, Ryu J. A revised scoring system for preoperative evaluation of metastatic spine tumor prognosis. Spine (Phila Pa 1976). 2005 Oct 1;30(19):2186-91. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Days of treatment	measurement of therapy related treatment days both as ambulatory and admitted to the hospital	52 weeks
Primary	Ability to walk	Ability to walk determined by EQ-5D-5L	6 weeks
Secondary	Self reported pain	self reported pain determined by EQ-5D-5L	0, 6, 12, 26, 52 weeks
Secondary	Self reported bladder control	reported by questionnaire	0, 6, 12, 26, 52 weeks
Secondary	Quality of life	QOL determined by EQ-5D-5L	0, 6, 12, 26, 52
Secondary	Response rate	Post interventional MRI scan with response classified according to RECIST 1.1	6 weeks
Secondary	Toxicity and interventional related complications	Determined by CTCAE 4.0	0, 6, 12, 26, 52 weeks