Randomized controlled trial

Maranzano E, Bellavita R, Rossi R, De A, V, Frattegiani A, Bagnoli R, Mignogna M, Beneventi S, Lupattelli M, Ponticelli P, Biti GP, Latini P (2005) Short-course versus split-course radiotherapy in metastatic spinal cord compression: results of a phase III, randomized, multicenter trial. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 23, 3358–3365
Design: RCT (1998– 2002)Level 1−
Country: Italy
setting: Multicentre
Aim: Hypofractionated radiotherapy (RT) is often used in the treatment of metastatic spinal cord compression (MSCC). This randomized trial was planned to assess the clinical outcome and toxicity of two different hypofractionated RT regimens in MSCC
Inclusion criteria MSCC diagnosed by MRI or CT, and clinical features, short life expectancy < 6 months
Exclusion criteria spinal instability, vertebral body collapse causing cord or nerve root compression, previous irradiation in same area
Population 300 randomized 276 (92%) assessable
Patients well balanced for age, gender, performance status, ambulatory status, histology (data not reported).
99 (36%) had favourable histology:
Prostate39/276 (14%)
Breast28/276 (10%)
Myeloma19/276 (7%)
Small cell lung8/276 (3%)
Lymphoma6/276 (2%)
177 (64%) had unfavourable histology:
Non-small cell lung177/276 (28%)
Colorectal25/276 (9%)
Kidney22/276 (8%)
Gastric11/276 (4%)
Head and neck7/276 (2.5%)
Liver7/276 (2.5%)
Bladder6/276 (2%)
Sarcoma6/276 (2%)
Melanoma3/276 (1.5%)
Uterine3/276 (1.5%)
Other14/276 (5%)
Site of MSCC
Location in spineLocation of metastases
Cervical8%Spine72/276 (26%)
Thoracic50%Multiple bone metastases113/276 (41%)
Lumbar23%Bone and visceral metastases91/276 (33%)
Sacral7%
Cervicothoracic1%
Thoracolumbar6%
Lumbosacral2%
Interventions:
Short course (8 Gy × 2 days) vs. split course RT (5 Gy × 3; 3 Gy × 5).

Outcomes
Ambulation
Motor performance (Tomita I to IV):
  1. ability to walk without support
  2. ability to walk with support
  3. inability to walk
  4. paraplegic
Bladder function – need of catheter
Pain: no pain; pain controlled with minor analgesics; pain requiring narcotics

Response criteria:
Responders- recovery or maintenance of walking ability, sphincter function.
3 categories for back pain- complete, partial, non-response

Survival
Pain relief

Follow up -1 month after RT, then monthly for 1 year.
Median follow-up 33 months (range 4–61mths)

Results

RT response
A total of 276 (92%) patients were assessable; 142 (51%) treated with the short- course and 134 (49%) treated with the split-course RT regimen.

There was no significant difference in response, duration of response, survival, or toxicity found between the two arms. When short- versus split-course regimens were compared, after RT 56% and 59% patients had back pain relief, 68% and 71% were able to walk, and 90% and 89% had good bladder function, respectively.

Survival
Median survival was 4 months and median duration of improvement was 3.5 months for both arms.

Survival time was significantly associated with walking ability pre and post treatment and favourable histology.

Percent probability of survival (Kaplan-Meier):
Patient group N=2761 year2 years3 yearsMedian survival (months)P
Pre-treatment status:
Walking n=18415%10%5%5
Non-walking n=9210%6%0%30.025
Post-treatment status:
Walking n=19318%10%6%5
Non-walking n=835%0%0%20.0001
Histology:
Favourable n=9630%30%8%6
Unfavourable n=1805%5%2%30.0001
Pain relief
Achieved in 157 patients(56.9%; 95%CI 51.1 – 62.7)
Complete response in 92(33.3%; 95%CI 27.7 – 38.9)
Partial response in 65(23.6%; 95%CI 18.6 – 28.6)
Motor function
Responders192 (69.6%; 95%CI 63.9 – 75.3)
Grade I93% maintained function
Grade II88% maintained function
Grade III35% regained motor ability
Grade IVNone of the 17 paraplegics improved
The median duration of motor capacity improvement was independent of the patient’s walking capacity. Only primary tumour type influenced the median duration of motor capacity improvement which was 6 months for favourable histologies and 3 months for unfavourable histologies (P= 0.0001).

Median duration of improvement in motor capacity:
Patient group% of respondersMedian duration of improvement (months)P value
Post treatment walking704
Pre-treatment status:
Walking914
Non-walking283
Histology:
Favourable766
Non-favourable6630.0001
Sphincter dysfunction
29 patients had sphincter dysfunction:
Response rate 89%
4 (14%) regained control
4 (2%) of those with good bladder control worsened
The remainder maintained bladder control

General comments

Authors conclusions
Both hypofractionated RT schedules adopted were effective and had acceptable toxicity. However, considering the advantages of the short-course regimen in terms of patient convenience and machine time, it could become the RT regimen of choice in the clinical practice for MSCC patients
Graham, P. H., Capp, A., Delaney, G., Goozee, G., Hickey, B., Turner, S., Browne, L., Milross, C. & Wirth, A. (2006) A pilot randomised comparison of dexamethasone 96 mg vs 16 mg per day for malignant spinal-cord compression treated by radiotherapy: TROG 01.05 Superdex study. Clinical oncology (Royal College of Radiologists (Great Britain)), 18: 70–76.
Design: RCT (Sept 2001–Nov 2003)Level 1−
Country: Australia, setting: 8 recruiting centres in 3 Australian states.

Aim:
One of the objectives was to determine which of several functional outcomes were more useful in discriminating clinically relevant outcome differences compared with ambulation.
Inclusion criteria Histological proof of malignancy, MRI, and at least one of pain, weakness, sensory symptoms, sphincter disturbance. Eastern Co-operative Oncology Group (ECOG) performance status of less than 4 before MSCC, minimum survival of 2 months.
Exclusion criteria Prior RT within one vertebral level, prior treatment for MSCC, multi-level MSCC or other CNS disease, lymphoma or myeloma histology, peptic ulceration, cardiac failure, patients undergoing surgery.
Population number of patients = 130 patients screened, 38 eligible and only 20 were randomised. Mean age 66 years (41–81). 14/20 (70%) were male.
11/20 (55%) had breast or prostate cancers.
15/20 (75%) were ambulant.
Interventions Radiotherapy – dose 30Gy in 10 fractions. One arm received 96mg iv dexamethasone, the other arm 16 mg for 2 days, then reduced to 0 mg by day 15.
Outcomes
Ambulation at 1 month
Functional indices of the Barthel Index, Functional Improvement Measure (FIM),
Functional Improvement Score (FIS), pain score.
Follow up At I month and at death.
Results
Survival
Median survival 2.3 months.
Survival was better for breast and prostate compared with other histologies:
10.6 vs 2.1 months; Hazard ratio 0.19 (0.06–0.66, p=0.01)
ambulant vs non-ambulant at baseline 5.9 vs 1.0 months HR 0.22 (0.07–0.72, p=0.01)
In a multivariate analysis histology and baseline ambulation were significant.
Survival by low or high dose dexamethasone was not significant.

From: Chapter 6, Treatment Selection and Strategies

Cover of Metastatic Spinal Cord Compression
Metastatic Spinal Cord Compression: Diagnosis and Management of Patients at Risk of or with Metastatic Spinal Cord Compression.
NICE Clinical Guidelines, No. 75.
National Collaborating Centre for Cancer (UK).
Copyright © 2008, National Collaborating Centre for Cancer.

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