Metastatic Epidural Spinal Cord Compression
Conditions
Keywords
metastatic epidural spinal cord compression, motor function, ambulatory status, pain, quality of life, overall survival, local control, toxicity
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.
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
Interventions
RADIATIONradiotherapy
external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)
Sponsors
Prof. Dirk Rades, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 89 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Showing Improvement or no Further Progression of Motor Deficits at 1 Month Following Radiotherapy | 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Were Alive at 6 Months Following Radiotherapy | 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. |
| Number of Participants Who Were Able to Walk at 1 Month Following Radiotherapy | 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.. |
| 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 | 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. |
| Number of Participants Who Experienced Relief of Pain at 1 Month Following Radiotherapy Compared to Baseline | 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. |
| Number of Participants Showing Improvement of Motor Deficits at 1 Month Following Radiotherapy | 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. |
| Number of Participants Experiencing at Least One Grade >=2 Radiotherapy-related Toxicity | during radiotherapy and up to 6 months following radiotherapy | Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) (version 4) |
| Number of Participants Who Experienced Relief of Distress at 1 Month Following Radiotherapy Compared to Baseline | 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. |
Countries
Germany, Lithuania, Saudi Arabia, Slovenia, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 5 x 4 Gy in 1 Week radiotherapy with 5 x 4 Gy in 1 week (5 x 4 Gy per week)
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy) | 101 |
| 10 x 3 Gy in 2 Weeks radiotherapy with 10 x 3 Gy in 2 weeks (5 x 3 Gy per week)
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy) | 102 |
| Total | 203 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 22 | 23 |
| Overall Study | Lost to Follow-up | 1 | 2 |
Baseline characteristics
| Characteristic | 5 x 4 Gy in 1 Week | 10 x 3 Gy in 2 Weeks | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 62 Participants | 67 Participants | 129 Participants |
| Age, Categorical Between 18 and 65 years | 39 Participants | 34 Participants | 73 Participants |
| Region of Enrollment Germany | 75 participants | 89 participants | 164 participants |
| Region of Enrollment Lithuania | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Slovenia | 8 participants | 9 participants | 17 participants |
| Region of Enrollment Spain | 17 participants | 4 participants | 21 participants |
| Sex: Female, Male Female | 41 Participants | 38 Participants | 79 Participants |
| Sex: Female, Male Male | 60 Participants | 64 Participants | 124 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 58 / 101 | 62 / 102 |
| other Total, other adverse events | 25 / 101 | 26 / 102 |
| serious Total, serious adverse events | 12 / 101 | 7 / 102 |
Outcome results
Primary
Number of Participants Showing Improvement or no Further Progression of Motor Deficits 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).
Time frame: at 1 month following radiotherapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 5 x 4 Gy in 1 Week | Number of Participants Showing Improvement or no Further Progression of Motor Deficits at 1 Month Following Radiotherapy | 68 Participants |
| 10 x 3 Gy in 2 Weeks | Number of Participants Showing Improvement or no Further Progression of Motor Deficits at 1 Month Following Radiotherapy | 69 Participants |
Secondary
Number of Participants Experiencing at Least One Grade >=2 Radiotherapy-related Toxicity
Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) (version 4)
Time frame: during radiotherapy and up to 6 months following radiotherapy
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 5 x 4 Gy in 1 Week | Number of Participants Experiencing at Least One Grade >=2 Radiotherapy-related Toxicity | at least 1 grade >=2 radiotherapy-related toxicity | 11 Participants |
| 5 x 4 Gy in 1 Week | Number of Participants Experiencing at Least One Grade >=2 Radiotherapy-related Toxicity | no grade >=2 radiotherapy-related toxicity | 90 Participants |
| 10 x 3 Gy in 2 Weeks | Number of Participants Experiencing at Least One Grade >=2 Radiotherapy-related Toxicity | at least 1 grade >=2 radiotherapy-related toxicity | 15 Participants |
| 10 x 3 Gy in 2 Weeks | Number of Participants Experiencing at Least One Grade >=2 Radiotherapy-related Toxicity | no grade >=2 radiotherapy-related toxicity | 87 Participants |
Secondary
Number of Participants Showing Improvement of Motor Deficits 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.
Time frame: at 1 month following radiotherapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 5 x 4 Gy in 1 Week | Number of Participants Showing Improvement of Motor Deficits at 1 Month Following Radiotherapy | 30 Participants |
| 10 x 3 Gy in 2 Weeks | Number of Participants Showing Improvement of Motor Deficits at 1 Month Following Radiotherapy | 34 Participants |
Secondary
Number of Participants Who Experienced Relief of Distress at 1 Month Following Radiotherapy Compared to Baseline
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.
Time frame: at 1 month following radiotherapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 5 x 4 Gy in 1 Week | Number of Participants Who Experienced Relief of Distress at 1 Month Following Radiotherapy Compared to Baseline | 43 Participants |
| 10 x 3 Gy in 2 Weeks | Number of Participants Who Experienced Relief of Distress at 1 Month Following Radiotherapy Compared to Baseline | 47 Participants |
Secondary
Number of Participants Who Experienced Relief of Pain at 1 Month Following Radiotherapy Compared to Baseline
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.
Time frame: at 1 month following radiotherapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 5 x 4 Gy in 1 Week | Number of Participants Who Experienced Relief of Pain at 1 Month Following Radiotherapy Compared to Baseline | 36 Participants |
| 10 x 3 Gy in 2 Weeks | Number of Participants Who Experienced Relief of Pain at 1 Month Following Radiotherapy Compared to Baseline | 40 Participants |
Secondary
Number of Participants Who Were Able to Walk 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..
Time frame: at 1 month following radiotherapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 5 x 4 Gy in 1 Week | Number of Participants Who Were Able to Walk at 1 Month Following Radiotherapy | 56 Participants |
| 10 x 3 Gy in 2 Weeks | Number of Participants Who Were Able to Walk at 1 Month Following Radiotherapy | 57 Participants |
Secondary
Number of Participants Who Were Alive at 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.
Time frame: 6 months following radiotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 x 4 Gy in 1 Week | Number of Participants Who Were Alive at 6 Months Following Radiotherapy | 42.3 Percentage of participants |
| 10 x 3 Gy in 2 Weeks | Number of Participants Who Were Alive at 6 Months Following Radiotherapy | 37.8 Percentage of participants |
Secondary
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
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.
Time frame: 6 months following radiotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 x 4 Gy in 1 Week | 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 | 75.2 Percentage of participants |
| 10 x 3 Gy in 2 Weeks | 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 | 81.8 Percentage of participants |