(ICORG 05-03): prospective randomized non-inferiority phase III trial comparing two radiation schedules in malignant spinal cord compression (not proceeding with surgical decompression); the quality of life analysis

Lee, K A; Dunne, Mary; Small, Cliona; Kelly, Paul; McArdle, O.; Hacking, D.; Pomeroy, M.; Armstrong, John G.; Moriarty, M.; Clayton-Lea, A.; Parker, Imelda; Collins, Conor D; Thirion, P.

doi:10.1080/0284186x.2018.1433320

Cited by 27 publications

(11 citation statements)

References 29 publications

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“…The primary trial objective was to show that ambulatory response rate using a single 8-Gy fraction of radiotherapy was noninferior to a total of 20 Gy of radiotherapy over 5 consecutive days (1 fraction per day) at 8 weeks. Assuming an ambulatory response rate (grade 1 or 2) of 75% of participants in both groups and a noninferiority margin of −11% (defined by consensus among the investigators, approved by the grant funder and the funder’s external reviewers, and similar to or less than noninferiority margins used in other trials), the trial required 386 patients (193 per group) assessable at 8 weeks with 80% power and 1-sided 5% statistical significance. The sample size was inflated to 580 allowing for 33% of participants to die before 8 weeks and later increased to 700 by the independent data monitoring committee because of a higher than anticipated death rate.…”

Section: Methodsmentioning

confidence: 99%

Effect of Single-Fraction vs Multifraction Radiotherapy on Ambulatory Status Among Patients With Spinal Canal Compression From Metastatic Cancer

Hoskin

Hopkins

Misra

et al. 2019

JAMA

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IMPORTANCE Malignant spinal canal compression, a major complication of metastatic cancer, is managed with radiotherapy to maintain mobility and relieve pain, although there is no standard radiotherapy regimen. OBJECTIVE To evaluate whether single-fraction radiotherapy is noninferior to 5 fractions of radiotherapy. DESIGN, SETTING, AND PARTICIPANTS Multicenter noninferiority randomized clinical trial conducted in 42 UK and 5 Australian radiotherapy centers. Eligible patients (n = 686) had metastatic cancer with spinal cord or cauda equina compression, life expectancy greater than 8 weeks, and no previous radiotherapy to the same area. Patients were recruited between February 2008 and April 2016, with final follow-up in September 2017. INTERVENTIONS Patients were randomized to receive external beam single-fraction 8-Gy radiotherapy (n = 345) or 20 Gy of radiotherapy in 5 fractions over 5 consecutive days (n = 341). MAIN OUTCOMES AND MEASURES The primary end point was ambulatory status at week 8, based on a 4-point scale and classified as grade 1 (ambulatory without the use of aids and grade 5 of 5 muscle power) or grade 2 (ambulatory using aids or grade 4 of 5 muscle power). The noninferiority margin for the difference in ambulatory status was −11%. Secondary end points included ambulatory status at weeks 1, 4, and 12 and overall survival. RESULTS Among 686 randomized patients (median [interquartile range] age, 70 [64-77] years; 503 (73%) men; 44% had prostate cancer, 19% had lung cancer, and 12% had breast cancer), 342 (49.8%) were analyzed for the primary end point (255 patients died before the 8-week assessment). Ambulatory status grade 1 or 2 at week 8 was achieved by 115 of 166 (69.3%) patients in the single-fraction group vs 128 of 176 (72.7%) in the multifraction group (difference, −3.5% [1-sided 95% CI, −11.5% to ϱ]; P value for noninferiority = .06). The difference in ambulatory status grade 1 or 2 in the single-fraction vs multifraction group was −0.4% (63.9% vs 64.3%; [1-sided 95% CI, −6.9 to ϱ]; P value for noninferiority = .004) at week 1, −0.7% (66.8% vs 67.6%; [1-sided 95% CI, −8.1 to ϱ]; P value for noninferiority = .01) at week 4, and 4.1% (71.8% vs 67.7%; [1-sided 95% CI, −4.6 to ϱ]; P value for noninferiority = .002) at week 12. Overall survival rates at 12 weeks were 50% in the single-fraction group vs 55% in the multifraction group (stratified hazard ratio, 1.02 [95% CI, 0.74-1.41]). Of the 11 other secondary end points that were analyzed, the between-group differences were not statistically significant or did not meet noninferiority criterion. CONCLUSIONS AND RELEVANCE Among patients with malignant metastatic solid tumors and spinal canal compression, a single radiotherapy dose, compared with a multifraction dose delivered over 5 days, did not meet the criterion for noninferiority for the primary outcome (ambulatory at 8 weeks). However, the extent to which the lower bound of the CI overlapped with the noninferiority margin should be considered when interpreting the clinical importance of this...

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Section: Methodsmentioning

confidence: 99%

Effect of Single-Fraction vs Multifraction Radiotherapy on Ambulatory Status Among Patients With Spinal Canal Compression From Metastatic Cancer

Hoskin

Hopkins

Misra

et al. 2019

JAMA

View full text Add to dashboard Cite

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“…The ICORG 05-03 phase 3, randomised, multicentre, noninferiority study compared a single dose of 10 Gy and 20 Gy in 5 fractions using a volume including a margin of at least one vertebra above and below the level of compression and dose prescribed to the depth of the cord [45]. Only 112 patients were enrolled and 73 were included in the analysis.…”

Section: Conventional External Beam Radiotherapymentioning

confidence: 99%

ESTRO ACROP guidelines for external beam radiotherapy of patients with complicated bone metastases

Oldenburger

Brown

Willmann

et al. 2022

Radiotherapy and Oncology

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“…Until now, three prospective phase III randomized clinical trials compared the effectiveness of SFRT versus MFRT in the treatment of MESCC (16)(17)(18), which demonstrated similarity in functional outcome. In Egypt, Abu-Hegazy et al They found no statistically significant difference in patientreported quality of life or pain scores at five weeks and at three months post treatment.…”

Section: Editorial Commentarymentioning

confidence: 99%

Towards answering the optimal palliative fractionation conundrum: single- versus multi-fraction radiation therapy for spinal cord compression

et al. 2020

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Patients with metastatic epidural spinal cord compression (MESCC) often present with loss of neurologic function, pain, and reduction in quality of life, all of which can be improved with palliative radiation therapy (1). A more prolonged treatment course for MESCC, typically delivered as 30 Gy in 10 fractions, has the advantage of delivering a higher biologically equivalent dose (BED), which could allow for more durable local control in a disease state where local control directly impacts spinal cord compromise and paralysis (2). However, many patients with MESCC have limited prognoses, and even one week of treatment may impose significant burdens for patients and their caregivers. As a result, shorter courses of palliative radiation therapy in this population can be desirable.S e v e r a l p r e v i o u s t r i a l s s p e c i f i c t o s i m p l e , o r uncomplicated bone metastases have demonstrated similar efficacy between single-fraction radiotherapy (SFRT) and multi-fraction radiotherapy (MFRT) for symptom relief (3-5). Radiation therapy can provide rapid responses for patients with uncomplicated bone metastases (6), and metaanalyses inclusive of over two dozen randomized trials from McMaster University, the Cochrane review, University of Toronto, and other international investigators have all concluded there is no significant difference in treatment response between .Despite increasing data from phase III randomized

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(ICORG 05-03): prospective randomized non-inferiority phase III trial comparing two radiation schedules in malignant spinal cord compression (not proceeding with surgical decompression); the quality of life analysis

Cited by 27 publications

References 29 publications

Effect of Single-Fraction vs Multifraction Radiotherapy on Ambulatory Status Among Patients With Spinal Canal Compression From Metastatic Cancer

Effect of Single-Fraction vs Multifraction Radiotherapy on Ambulatory Status Among Patients With Spinal Canal Compression From Metastatic Cancer

ESTRO ACROP guidelines for external beam radiotherapy of patients with complicated bone metastases

Towards answering the optimal palliative fractionation conundrum: single- versus multi-fraction radiation therapy for spinal cord compression

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