Non-inferiority randomised phase 3 trial comparing two radiation schedules (single vs. five fractions) in malignant spinal cord compression

Pierre G Thirion; Mary T Dunne; Paul J Kelly; Aileen Flavin; Joe M O'Sullivan; Dayle Hacking; Wojciech Sasiadek; Cormac Small; Maeve M Pomeroy; Joseph Martin; Orla McArdle; Imelda Parker; Lydia S O'Sullivan; Aoife M Shannon; Angela Clayton-Lea; Conor D Collins; Michael R Stevenson; Alberto Alvarez-Iglesias; John G Armstrong; Michael Moriarty

doi:10.1038/s41416-020-0768-z

Non-inferiority randomised phase 3 trial comparing two radiation schedules (single vs. five fractions) in malignant spinal cord compression

Pierre G Thirion, Mary T Dunne, Paul J Kelly, Aileen Flavin, Joe M O'Sullivan, Dayle Hacking, Wojciech Sasiadek, Cormac Small, Maeve M Pomeroy, Joseph Martin, Orla McArdle, Imelda Parker, Lydia S O'Sullivan, Aoife M Shannon, Angela Clayton-Lea, Conor D Collins, Michael R Stevenson, Alberto Alvarez-Iglesias, John G Armstrong, Michael Moriarty

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

BACKGROUND: The optimal EBRT schedule for MSCC is undetermined. Our aim was to determine whether a single fraction (SF) was non-inferior to five daily fractions (5Fx), for functional motor outcome.

METHODS: Patients not proceeding with surgical decompression in this multicentre non-inferiority, Phase 3 trial were randomised to 10 Gy/SF or 20 Gy/5Fx. A change in mobility from baseline to 5 weeks for each patient, was evaluated by a Modified Tomita score: 1 = 'Walk unaided', 2 = 'With walking aid' and 3 = 'Bed-bound'. The margin used to establish non-inferiority was a detrimental change of -0.4 in the mean difference between arms.

RESULTS: One-hundred and twelve eligible patients were enrolled. Seventy-three patients aged 30-87 were evaluated for the primary analysis. The 95% CI for the difference in the mean change in mobility scores between arms was -0.12 to 0.6. Since -0.4 is not included in the interval, there is evidence that 10 Gy/SF is non-inferior to 20 Gy/5Fx. One grade 3 AE was reported in the 5Fx arm. Twelve (26%) patients in the 5Fx arm had a Grade 2-3 AE compared with six (11%) patients in the SF arm (p = 0.093).

CONCLUSION: For mobility preservation, one 10-Gy fraction is non-inferior to 20 Gy in five fractions, in patients with MSCC not proceeding with surgical decompression.

CLINICAL TRIAL REGISTRATION: Cancer Trials Ireland ICORG 05-03; NCT00968643; EU-20952.

Original language	English
Journal	British Journal of Cancer
Early online date	11 Mar 2020
DOIs	https://doi.org/10.1038/s41416-020-0768-z
Publication status	Early online date - 11 Mar 2020
Externally published	Yes

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Thirion, P. G., Dunne, M. T., Kelly, P. J., Flavin, A., O'Sullivan, J. M., Hacking, D., Sasiadek, W., Small, C., Pomeroy, M. M., Martin, J., McArdle, O., Parker, I., O'Sullivan, L. S., Shannon, A. M., Clayton-Lea, A., Collins, C. D., Stevenson, M. R., Alvarez-Iglesias, A., Armstrong, J. G., & Moriarty, M. (2020). Non-inferiority randomised phase 3 trial comparing two radiation schedules (single vs. five fractions) in malignant spinal cord compression. British Journal of Cancer. https://doi.org/10.1038/s41416-020-0768-z

Thirion, Pierre G ; Dunne, Mary T ; Kelly, Paul J ; Flavin, Aileen ; O'Sullivan, Joe M ; Hacking, Dayle ; Sasiadek, Wojciech ; Small, Cormac ; Pomeroy, Maeve M ; Martin, Joseph ; McArdle, Orla ; Parker, Imelda ; O'Sullivan, Lydia S ; Shannon, Aoife M ; Clayton-Lea, Angela ; Collins, Conor D ; Stevenson, Michael R ; Alvarez-Iglesias, Alberto ; Armstrong, John G ; Moriarty, Michael. / Non-inferiority randomised phase 3 trial comparing two radiation schedules (single vs. five fractions) in malignant spinal cord compression. In: British Journal of Cancer. 2020.

@article{04eb70b3a13e4edc90668734fc514126,

title = "Non-inferiority randomised phase 3 trial comparing two radiation schedules (single vs. five fractions) in malignant spinal cord compression",

abstract = "BACKGROUND: The optimal EBRT schedule for MSCC is undetermined. Our aim was to determine whether a single fraction (SF) was non-inferior to five daily fractions (5Fx), for functional motor outcome.METHODS: Patients not proceeding with surgical decompression in this multicentre non-inferiority, Phase 3 trial were randomised to 10 Gy/SF or 20 Gy/5Fx. A change in mobility from baseline to 5 weeks for each patient, was evaluated by a Modified Tomita score: 1 = 'Walk unaided', 2 = 'With walking aid' and 3 = 'Bed-bound'. The margin used to establish non-inferiority was a detrimental change of -0.4 in the mean difference between arms.RESULTS: One-hundred and twelve eligible patients were enrolled. Seventy-three patients aged 30-87 were evaluated for the primary analysis. The 95% CI for the difference in the mean change in mobility scores between arms was -0.12 to 0.6. Since -0.4 is not included in the interval, there is evidence that 10 Gy/SF is non-inferior to 20 Gy/5Fx. One grade 3 AE was reported in the 5Fx arm. Twelve (26%) patients in the 5Fx arm had a Grade 2-3 AE compared with six (11%) patients in the SF arm (p = 0.093).CONCLUSION: For mobility preservation, one 10-Gy fraction is non-inferior to 20 Gy in five fractions, in patients with MSCC not proceeding with surgical decompression.CLINICAL TRIAL REGISTRATION: Cancer Trials Ireland ICORG 05-03; NCT00968643; EU-20952.",

author = "Thirion, {Pierre G} and Dunne, {Mary T} and Kelly, {Paul J} and Aileen Flavin and O'Sullivan, {Joe M} and Dayle Hacking and Wojciech Sasiadek and Cormac Small and Pomeroy, {Maeve M} and Joseph Martin and Orla McArdle and Imelda Parker and O'Sullivan, {Lydia S} and Shannon, {Aoife M} and Angela Clayton-Lea and Collins, {Conor D} and Stevenson, {Michael R} and Alberto Alvarez-Iglesias and Armstrong, {John G} and Michael Moriarty",

year = "2020",

month = mar,

day = "11",

doi = "10.1038/s41416-020-0768-z",

language = "English",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

}

Thirion, PG, Dunne, MT, Kelly, PJ, Flavin, A, O'Sullivan, JM, Hacking, D, Sasiadek, W, Small, C, Pomeroy, MM, Martin, J, McArdle, O, Parker, I, O'Sullivan, LS, Shannon, AM, Clayton-Lea, A, Collins, CD, Stevenson, MR, Alvarez-Iglesias, A, Armstrong, JG & Moriarty, M 2020, 'Non-inferiority randomised phase 3 trial comparing two radiation schedules (single vs. five fractions) in malignant spinal cord compression', British Journal of Cancer. https://doi.org/10.1038/s41416-020-0768-z

Non-inferiority randomised phase 3 trial comparing two radiation schedules (single vs. five fractions) in malignant spinal cord compression. / Thirion, Pierre G; Dunne, Mary T; Kelly, Paul J; Flavin, Aileen; O'Sullivan, Joe M; Hacking, Dayle; Sasiadek, Wojciech; Small, Cormac; Pomeroy, Maeve M; Martin, Joseph; McArdle, Orla; Parker, Imelda; O'Sullivan, Lydia S; Shannon, Aoife M; Clayton-Lea, Angela; Collins, Conor D; Stevenson, Michael R; Alvarez-Iglesias, Alberto; Armstrong, John G; Moriarty, Michael.

In: British Journal of Cancer, 11.03.2020.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Non-inferiority randomised phase 3 trial comparing two radiation schedules (single vs. five fractions) in malignant spinal cord compression

AU - Thirion, Pierre G

AU - Dunne, Mary T

AU - Kelly, Paul J

AU - Flavin, Aileen

AU - O'Sullivan, Joe M

AU - Hacking, Dayle

AU - Sasiadek, Wojciech

AU - Small, Cormac

AU - Pomeroy, Maeve M

AU - Martin, Joseph

AU - McArdle, Orla

AU - Parker, Imelda

AU - O'Sullivan, Lydia S

AU - Shannon, Aoife M

AU - Clayton-Lea, Angela

AU - Collins, Conor D

AU - Stevenson, Michael R

AU - Alvarez-Iglesias, Alberto

AU - Armstrong, John G

AU - Moriarty, Michael

PY - 2020/3/11

Y1 - 2020/3/11

N2 - BACKGROUND: The optimal EBRT schedule for MSCC is undetermined. Our aim was to determine whether a single fraction (SF) was non-inferior to five daily fractions (5Fx), for functional motor outcome.METHODS: Patients not proceeding with surgical decompression in this multicentre non-inferiority, Phase 3 trial were randomised to 10 Gy/SF or 20 Gy/5Fx. A change in mobility from baseline to 5 weeks for each patient, was evaluated by a Modified Tomita score: 1 = 'Walk unaided', 2 = 'With walking aid' and 3 = 'Bed-bound'. The margin used to establish non-inferiority was a detrimental change of -0.4 in the mean difference between arms.RESULTS: One-hundred and twelve eligible patients were enrolled. Seventy-three patients aged 30-87 were evaluated for the primary analysis. The 95% CI for the difference in the mean change in mobility scores between arms was -0.12 to 0.6. Since -0.4 is not included in the interval, there is evidence that 10 Gy/SF is non-inferior to 20 Gy/5Fx. One grade 3 AE was reported in the 5Fx arm. Twelve (26%) patients in the 5Fx arm had a Grade 2-3 AE compared with six (11%) patients in the SF arm (p = 0.093).CONCLUSION: For mobility preservation, one 10-Gy fraction is non-inferior to 20 Gy in five fractions, in patients with MSCC not proceeding with surgical decompression.CLINICAL TRIAL REGISTRATION: Cancer Trials Ireland ICORG 05-03; NCT00968643; EU-20952.

AB - BACKGROUND: The optimal EBRT schedule for MSCC is undetermined. Our aim was to determine whether a single fraction (SF) was non-inferior to five daily fractions (5Fx), for functional motor outcome.METHODS: Patients not proceeding with surgical decompression in this multicentre non-inferiority, Phase 3 trial were randomised to 10 Gy/SF or 20 Gy/5Fx. A change in mobility from baseline to 5 weeks for each patient, was evaluated by a Modified Tomita score: 1 = 'Walk unaided', 2 = 'With walking aid' and 3 = 'Bed-bound'. The margin used to establish non-inferiority was a detrimental change of -0.4 in the mean difference between arms.RESULTS: One-hundred and twelve eligible patients were enrolled. Seventy-three patients aged 30-87 were evaluated for the primary analysis. The 95% CI for the difference in the mean change in mobility scores between arms was -0.12 to 0.6. Since -0.4 is not included in the interval, there is evidence that 10 Gy/SF is non-inferior to 20 Gy/5Fx. One grade 3 AE was reported in the 5Fx arm. Twelve (26%) patients in the 5Fx arm had a Grade 2-3 AE compared with six (11%) patients in the SF arm (p = 0.093).CONCLUSION: For mobility preservation, one 10-Gy fraction is non-inferior to 20 Gy in five fractions, in patients with MSCC not proceeding with surgical decompression.CLINICAL TRIAL REGISTRATION: Cancer Trials Ireland ICORG 05-03; NCT00968643; EU-20952.

U2 - 10.1038/s41416-020-0768-z

DO - 10.1038/s41416-020-0768-z

M3 - Article

C2 - 32157242

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

ER -

Non-inferiority randomised phase 3 trial comparing two radiation schedules (single vs. five fractions) in malignant spinal cord compression

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