Radiotherapy of Motor Deficits From Metastatic Epidural Spinal Cord Compression (SCORE-2)

• ClinicalTrials.gov Identifier: NCT02189473
• Recruitment Status: Completed
• First Posted: July 14, 2014
• Results First Posted: February 17, 2020
• Last Update Posted: March 5, 2020
• Sponsor: Prof. Dirk Rades, MD
• Information provided by (Responsible Party): Prof. Dirk Rades, MD, University Hospital Schleswig-Holstein

Study Description

Brief Summary:

The primary aim of this randomized multi-center trial is to investigate the efficacy of the radiotherapy regimens 5 x 4 Gy and 10 x 3 Gy with respect to the effect on motor function in patients with metastatic epidural spinal cord compression.

Condition or disease	Intervention/treatment	Phase
Metastatic Epidural Spinal Cord Compression	Radiation: radiotherapy	Not Applicable

Detailed Description:

The primary aim of this randomized multi-center trial is to investigate the efficacy of the radiotherapy regimens 5 x 4 Gy and 10 x 3 Gy with respect to the effect on motor function in patients with metastatic epidural spinal cord compression. The response rate (improvement in motor function or prevention of progression) will be assessed at one month following radiotherapy.

In addition, the following endpoints will be evaluated:

1. Motor function; additional assessments directly and at 3 and at 6 months after radiotherapy
2. Ability to walk; assessment directly and at 1, 3 and 6 months after radiotherapy
3. Sensory function; assessment directly and at 1, 3 and 6 months after radiotherapy
4. Quality of life; evaluation directly and at 1, 3 and 6 months after radiotherapy
5. Pain assessment directly and at 1, 3 and 6 months after radiotherapy
6. Overall survival up to 6 months following radiotherapy
7. Local Progression-free survival up to 6 months following radiotherapy

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 203 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Radiotherapy of Motor Deficits From Metastatic Epidural Spinal Cord Compression (10 x 3 Gy Versus 5 x 4 Gy)
• Study Start Date: July 2010
• Actual Primary Completion Date: July 2015
• Actual Study Completion Date: July 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: 5 x 4 Gy in 1 week; radiotherapy with 5 x 4 Gy in 1 week (5 x 4 Gy per week)	Radiation: radiotherapy; external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)
Active Comparator: 10 x 3 Gy in 2 weeks; radiotherapy with 10 x 3 Gy in 2 weeks (5 x 3 Gy per week)	Radiation: radiotherapy; external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)

Outcome Measures

Primary Outcome Measures :

1. Number of Participants Showing Improvement or no Further Progression of Motor Deficits at 1 Month Following Radiotherapy [ Time Frame: at 1 month following radiotherapy ]

   Overall response was defined as improvement or no further progression of motor deficits following radiotherapy.

   Motor function was graded with the following 8-point scale: 0, complete paraplegia; 1, palpable or visible muscle contractions; 2, active movement of the leg without gravity; 3, active movement against gravity; 4, active movement against mild resistance; 5, active movement against intermediate resistance; 6, active movement against strong resistance; and 7, normal strength.

   Motor function was recorded separately for each leg resulting in total points of 0 to 14. Improvement of motor function was defined as an increase by at least 2 points compared to baseline. No further progression was defined as +/-1 point (i.e. +1 point, +/- 0 points or -1 point).

Secondary Outcome Measures :

1. Number of Participants Who Were Able to Walk at 1 Month Following Radiotherapy [ Time Frame: at 1 month following radiotherapy ]

   Ambulatory status was assessed using the following scoring system:

   0 = Normal strength

   1. = Ambulatory without aid
   2. = Ambulatory with aid
   3. = Not ambulatory

   A patient with a score equal to or less than 2 is considered "able to walk". Both participants that could and could not walk prior to radiotherapy have been included in this assessment..

2. Number of Participants Who Were Alive at 6 Months Following Radiotherapy Without Deterioration of Motor Function During (or Directly Following) Radiotherapy and Freedom From In-field Recurrence of Metastatic Spinal Cord Compression Following Radiotherapy [ Time Frame: 6 months following radiotherapy ]

   Local Progression Free Survival (LPFS) was defined as freedom from progression of motor deficits during or one month following radiotherapy and freedom from in-field recurrence of metastatic spinal cord compression (MSCC) following radiotherapy.

   An in-field recurrence was defined as a recurrence of MSCC associated with motor deficits in the region of the spinal cord that had been previously irradiated for MSCC.

   In case of clinical suspicion of sich a recurrence, a spinal MRI was performed to confirm the diagnosis. Time to in-field recurrence was calculated from the last day of radiotherapy, and the patients were followed for a maximum of 6 months after the end of radiotherapy. The values of 6-month LPFS were estimated using the Kaplan-Meier method.

3. Number of Participants Who Experienced Relief of Distress at 1 Month Following Radiotherapy Compared to Baseline [ Time Frame: at 1 month following radiotherapy ]

   Distress (as an indicator of impairment of quality of life) was measured with the distress-thermometer. the patients rated their level of distress on a scale ranging from 0 (no distress) to 10 (extreme distress). Patients rated the distress they experienced during the last week and stated the reasons for distress from a list of items.

   An improvement (lower score) by 2 points was considered a clinically relevant relief of distress. Patients with baseline-scores of 0-1 points were not included, since improvement by 2 points was not possible.

4. Number of Participants Who Experienced Relief of Pain at 1 Month Following Radiotherapy Compared to Baseline [ Time Frame: at 1 month following radiotherapy ]

   Pain was measured with a numeric self-rating scale ranging from 0 (no pain) to 10 (worst pain).

   Relief of pain was defined as improvement (=decrease of pain) by at least 2 points without increase of analgesics. Patients with baseline-scores of 0-1 points were not included, since improvement by 2 points was not possible.

5. Number of Participants Who Were Alive at 6 Months Following Radiotherapy [ Time Frame: 6 months following radiotherapy ]

   Overall Survival (OS) was defined as freedom from death of any cause.

   Time to death was calculated from the last day of radiotherapy, and the patients were followed for a maximum of 6 months after the end of radiotherapy. The values of 6-month OS were estimated using the Kaplan-Meier method.

6. Number of Participants Showing Improvement of Motor Deficits at 1 Month Following Radiotherapy [ Time Frame: at 1 month following radiotherapy ]

   Motor function was graded with the following 8-point scale: 0, complete paraplegia; 1, palpable or visible muscle contractions; 2, active movement of the leg without gravity; 3, active movement against gravity; 4, active movement against mild resistance; 5, active movement against intermediate resistance; 6, active movement against strong resistance; and 7, normal strength.

   Motor function was recorded separately for each leg resulting in total points of 0 to 14. Improvement of motor function was defined as an increase by at least 2 points compared to baseline.

7. Number of Participants Experiencing at Least One Grade >=2 Radiotherapy-related Toxicity [ Time Frame: during radiotherapy and up to 6 months following radiotherapy ]
   Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) (version 4)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 89 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Motor deficits of the lower extremities resulting from metastatic epidural spinal cord compression, which have persisted for no longer than 30 days
• Confirmation of diagnosis by magnetic resonance imaging (spinal computed tomography allowed)
• Relatively poor survival prognosis (defined as ≤35 points on the survival score published in Cancer 2008)
• Written informed consent

Exclusion Criteria:

• Prior radiotherapy or surgery of the spinal areas affected by MESCC
• History of symptomatic brain tumor or symptomatic brain metastases
• Metastases of the cervical spine only
• Other severe neurological disorders
• Pregnancy, Lactation
• Indication for decompressive surgery + stabilization of the affected spinal areas

Contacts and Locations

Locations

United States, Arizona

Mayo Clinic

Scottsdale, Arizona, United States, 85259

Germany

Oberschwabenklinik Ravensburg

Ravensburg, Baden-Wutemberg, Germany, 88191

Klinikum Bayreuth

Bayreuth, Bavaria, Germany, 95445

University of Regensburg

Regensburg, Bavaria, Germany, 93053

University of Würzburg

Würzburg, Bavaria, Germany, 97080

Ruhr University

Bochum, North Rhine Westphalia, Germany, 44801

Radiotherapy Practice Dresden-Friedrichstadt

Dresden, Saxonia, Germany, 01067

University of Lübeck

Lübeck, Schleswig-Holstein, Germany, 23538

Charite Berlin

Berlin, Germany, 10117

Center of Radiotherapy and Radiation Oncology

Bremen, Germany, 28239

Lithuania

Institute of Oncology, Vilnius University

Vilnius, Lithuania

Saudi Arabia

Saad Specialist Hospital

Khobar, Saudi Arabia

Slovenia

Institute of Oncology

Ljubljana, Slovenia

Spain

Consorcio Hospitalario Provencial de Castellon

Valencia, Castellon, Spain

Cruces University Hospital

Barakaldo, Vizcaya (Basque Country), Spain, 48903

Sponsors and Collaborators

Prof. Dirk Rades, MD

Investigators

• Study Chair: Dirk Rades, MD; Department of Radiation Oncology, University of Lübeck, Germany

More Information

Publications:

Maranzano E, Latini P. Effectiveness of radiation therapy without surgery in metastatic spinal cord compression: final results from a prospective trial. Int J Radiat Oncol Biol Phys. 1995 Jul 15;32(4):959-67.

Sørensen S, Børgesen SE, Rohde K, Rasmusson B, Bach F, Bøge-Rasmussen T, Stjernholm P, Larsen BH, Agerlin N, Gjerris F, et al. Metastatic epidural spinal cord compression. Results of treatment and survival. Cancer. 1990 Apr 1;65(7):1502-8.

Helweg-Larsen S, Sørensen PS, Kreiner S. Prognostic factors in metastatic spinal cord compression: a prospective study using multivariate analysis of variables influencing survival and gait function in 153 patients. Int J Radiat Oncol Biol Phys. 2000 Mar 15;46(5):1163-9.

Leviov M, Dale J, Stein M, Ben-Shahar M, Ben-Arush M, Milstein D, Goldsher D, Kuten A. The management of metastatic spinal cord compression: a radiotherapeutic success ceiling. Int J Radiat Oncol Biol Phys. 1993 Sep 30;27(2):231-4.

Rades D, Blach M, Bremer M, Wildfang I, Karstens JH, Heidenreich F. Prognostic significance of the time of developing motor deficits before radiation therapy in metastatic spinal cord compression: one-year results of a prospective trial. Int J Radiat Oncol Biol Phys. 2000 Dec 1;48(5):1403-8.

Rades D, Heidenreich F, Bremer M, Karstens JH. Time of developing motor deficits before radiotherapy as a new and relevant prognostic factor in metastatic spinal cord compression: final results of a retrospective analysis. Eur Neurol. 2001;45(4):266-9.

Rades D, Heidenreich F, Karstens JH. Final results of a prospective study of the prognostic value of the time to develop motor deficits before irradiation in metastatic spinal cord compression. Int J Radiat Oncol Biol Phys. 2002 Jul 15;53(4):975-9.

Arcangeli G, Giovinazzo G, Saracino B, D'Angelo L, Giannarelli D, Arcangeli G, Micheli A. Radiation therapy in the management of symptomatic bone metastases: the effect of total dose and histology on pain relief and response duration. Int J Radiat Oncol Biol Phys. 1998 Dec 1;42(5):1119-26.

Niewald M, Tkocz HJ, Abel U, Scheib T, Walter K, Nieder C, Schnabel K, Berberich W, Kubale R, Fuchs M. Rapid course radiation therapy vs. more standard treatment: a randomized trial for bone metastases. Int J Radiat Oncol Biol Phys. 1996 Dec 1;36(5):1085-9.

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. Bone Pain Trial Working Party. Radiother Oncol. 1999 Aug;52(2):111-21.

Steenland E, Leer JW, van Houwelingen H, Post WJ, van den Hout WB, Kievit J, de Haes H, Martijn H, Oei B, Vonk E, van der Steen-Banasik E, Wiggenraad RG, Hoogenhout J, Wárlám-Rodenhuis C, van Tienhoven G, Wanders R, Pomp J, van Reijn M, van Mierlo I, Rutten E. 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 Aug;52(2):101-9. Erratum in: Radiother Oncol 1999 Nov;53(2):167. Leer, J [corrected to Leer, JW]; van Mierlo ,T [corrected to van Mierlo, I].

Rades D, Stalpers LJ, Veninga T, Schulte R, Hoskin PJ, Obralic N, Bajrovic A, Rudat V, Schwarz R, Hulshof MC, Poortmans P, Schild SE. Evaluation of five radiation schedules and prognostic factors for metastatic spinal cord compression. J Clin Oncol. 2005 May 20;23(15):3366-75.

Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, Shank B, Solin LJ, Wesson M. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991 May 15;21(1):109-22. Review.

Barendsen GW. Dose fractionation, dose rate and iso-effect relationships for normal tissue responses. Int J Radiat Oncol Biol Phys. 1982 Nov;8(11):1981-97. Review.

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 Oct;175(10):500-8. German.

Rades D, Dunst J, Schild SE. The first score predicting overall survival in patients with metastatic spinal cord compression. Cancer. 2008 Jan 1;112(1):157-61.

Tomita T, Galicich JH, Sundaresan N. Radiation therapy for spinal epidural metastases with complete block. Acta Radiol Oncol. 1983;22(2):135-43.

Maranzano E, Bellavita R, Rossi R, De Angelis V, Frattegiani A, Bagnoli R, Mignogna M, Beneventi S, Lupattelli M, Ponticelli P, Biti GP, Latini P. Short-course versus split-course radiotherapy in metastatic spinal cord compression: results of a phase III, randomized, multicenter trial. J Clin Oncol. 2005 May 20;23(15):3358-65. Epub 2005 Feb 28.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Rades D, Šegedin B, Conde-Moreno AJ, Ferrer-Albiach C, Metz M, Polat B, Badakhshi H, Schreiber A, Nitsche M, Cacicedo J, Schild SE. Patient-Reported Outcomes-Secondary Analysis of the SCORE-2 Trial Comparing 4 Gy × 5 to 3 Gy × 10 for Metastatic Epidural Spinal Cord Compression. Int J Radiat Oncol Biol Phys. 2019 Nov 15;105(4):760-764. doi: 10.1016/j.ijrobp.2019.08.002. Epub 2019 Aug 12.

Rades D, Šegedin B, Conde-Moreno AJ, Garcia R, Perpar A, Metz M, Badakhshi H, Schreiber A, Nitsche M, Hipp P, Schulze W, Adamietz IA, Norkus D, Rudat V, Cacicedo J, Schild SE. Radiotherapy With 4 Gy × 5 Versus 3 Gy × 10 for Metastatic Epidural Spinal Cord Compression: Final Results of the SCORE-2 Trial (ARO 2009/01). J Clin Oncol. 2016 Feb 20;34(6):597-602. doi: 10.1200/JCO.2015.64.0862. Epub 2016 Jan 4.

• Responsible Party: Prof. Dirk Rades, MD, Prof. Dr. Dirk Rades. MD, University Hospital Schleswig-Holstein
• ClinicalTrials.gov Identifier: NCT02189473
• Other Study ID Numbers: ARO 200901
• First Posted: July 14, 2014
• Results First Posted: February 17, 2020
• Last Update Posted: March 5, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Prof. Dirk Rades, MD, University Hospital Schleswig-Holstein:

metastatic epidural spinal cord compression; motor function; ambulatory status; pain; quality of life; overall survival; local control; toxicity

Additional relevant MeSH terms:

Spinal Cord Compression; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Injuries; Wounds and Injuries