dc.contributor.author | Brand, DH | |
dc.contributor.author | Brüningk, SC | |
dc.contributor.author | Wilkins, A | |
dc.contributor.author | Naismith, O | |
dc.contributor.author | Gao, A | |
dc.contributor.author | Syndikus, I | |
dc.contributor.author | Dearnaley, DP | |
dc.contributor.author | van As, N | |
dc.contributor.author | Hall, E | |
dc.contributor.author | Gulliford, S | |
dc.contributor.author | Tree, AC | |
dc.contributor.author | CHHiP Trial Management Group, | |
dc.date.accessioned | 2022-08-18T14:56:28Z | |
dc.date.available | 2022-08-18T14:56:28Z | |
dc.date.issued | 2023-02-01 | |
dc.identifier.citation | International Journal of Radiation: Oncology - Biology - Physics, | |
dc.identifier.issn | 0360-3016 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5279 | |
dc.description.abstract | PURPOSE: Moderately hypofractionated external beam intensity modulated radiation therapy (RT) for prostate cancer is now standard-of-care. Normal tissue toxicity responses to fraction size alteration are nonlinear: the linear-quadratic model is a widely used framework accounting for this, through the α/β ratio. Few α/β ratio estimates exist for human late genitourinary endpoints; here we provide estimates derived from a hypofractionation trial. METHODS AND MATERIALS: The CHHiP trial randomized 3216 men with localized prostate cancer 1:1:1 between conventionally fractionated intensity modulated RT (74 Gy/37 fractions (Fr)) and 2 moderately hypofractionated regimens (60 Gy/20 Fr and 57 Gy/19 Fr). RT plan and suitable follow-up assessment was available for 2206 men. Three prospectively assessed clinician-reported toxicity scales were amalgamated for common genitourinary endpoints: dysuria, hematuria, incontinence, reduced flow/stricture, and urine frequency. Per endpoint, only patients with baseline zero toxicity were included. Three models for endpoint grade ≥1 (G1+) and G2+ toxicity were fitted: Lyman Kutcher-Burman (LKB) without equivalent dose in 2 Gy/Fr (EQD2) correction [LKB-NoEQD2]; LKB with EQD2-correction [LKB-EQD2]; LKB-EQD2 with dose-modifying-factor (DMF) inclusion [LKB-EQD2-DMF]. DMFs were age, diabetes, hypertension, pelvic surgery, prior transurethral resection of prostate (TURP), overall treatment time and acute genitourinary toxicity (G2+). Bootstrapping generated 95% confidence intervals and unbiased performance estimates. Models were compared by likelihood ratio test. RESULTS: The LKB-EQD2 model significantly improved performance over LKB-NoEQD2 for just 3 endpoints: dysuria G1+ (α/β = 2.0 Gy; 95% confidence interval [CI], 1.2-3.2 Gy), hematuria G1+ (α/β = 0.9 Gy; 95% CI, 0.1-2.2 Gy) and hematuria G2+ (α/β = 0.6 Gy; 95% CI, 0.1-1.7 Gy). For these 3 endpoints, further incorporation of 2 DMFs improved on LKB-EQD2: acute genitourinary toxicity and prior TURP (hematuria G1+ only), but α/β ratio estimates remained stable. CONCLUSIONS: Inclusion of EQD2-correction significantly improved model fitting for dysuria and hematuria endpoints, where fitted α/β ratio estimates were low: 0.6 to 2 Gy. This suggests therapeutic gain for clinician-reported GU toxicity, through hypofractionation, might be lower than expected by typical late α/β ratio assumptions of 3 to 5 Gy. | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER SCIENCE INC | |
dc.relation.ispartof | International Journal of Radiation: Oncology - Biology - Physics | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.title | The Fraction Size Sensitivity of Late Genitourinary Toxicity: Analysis of Alpha/Beta (α/β) Ratios in the CHHiP Trial. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-08-11 | |
dc.date.updated | 2022-08-18T12:02:46Z | |
rioxxterms.version | AM | |
rioxxterms.type | Journal Article/Review | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Stereotactic and Precision Body Radiotherapy | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/17/18 Starting Cohort | |
pubs.publication-status | Accepted | |
icr.researchteam | Clin Trials & Stats Unit | |
icr.researchteam | Stereotactic Radiother | |
dc.contributor.icrauthor | Brand, Douglas | |
dc.contributor.icrauthor | Corbett, Anna | |
dc.contributor.icrauthor | Gao, Annie | |
dc.contributor.icrauthor | Dearnaley, David | |
dc.contributor.icrauthor | Hall, Emma | |
icr.provenance | Deposited by Dr Doug Brand on 2022-08-18. Deposit type is initial. No. of files: 1. Files: MANUSCRIPT_FINAL_Blinded_rv1_NoMarkup.docx | |
icr.provenance | Deposited by Mr Arek Surman (impersonating Dr Doug Brand) on 2022-08-18. Deposit type is subsequent. No. of files: 2. Files: MANUSCRIPT_FINAL_Blinded_rv1_NoMarkup (1).pdf; Supplement_rv1.pdf | |