dc.contributor.author | Brand, DH | |
dc.contributor.author | Brüningk, SC | |
dc.contributor.author | Wilkins, A | |
dc.contributor.author | Fernandez, K | |
dc.contributor.author | Naismith, O | |
dc.contributor.author | Gao, A | |
dc.contributor.author | Syndikus, I | |
dc.contributor.author | Dearnaley, DP | |
dc.contributor.author | Tree, AC | |
dc.contributor.author | van As, N | |
dc.contributor.author | Hall, E | |
dc.contributor.author | Gulliford, S | |
dc.contributor.author | CHHiP Trial Management Group, | |
dc.date.accessioned | 2021-01-12T10:28:15Z | |
dc.date.issued | 2021-06-01 | |
dc.identifier.citation | International journal of radiation oncology, biology, physics, 2021 | |
dc.identifier.issn | 0360-3016 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4277 | |
dc.identifier.eissn | 1879-355X | |
dc.identifier.doi | 10.1016/j.ijrobp.2020.12.041 | |
dc.description.abstract | PURPOSE: Changes in fraction size of external beam radiation therapy exert nonlinear effects on subsequent toxicity. Commonly described by the linear-quadratic model, fraction size sensitivity of normal tissues is expressed by the α/β ratio. We sought to study individual α/β ratios for different late rectal effects after prostate external beam radiation therapy. METHODS AND MATERIALS: The CHHiP trial (ISRCTN97182923) randomized men with nonmetastatic prostate cancer 1:1:1 to 74 Gy/37 fractions (Fr), 60 Gy/20 Fr, or 57 Gy/19 Fr. Patients in the study had full dosimetric data and zero baseline toxicity. Toxicity scales were amalgamated to 6 bowel endpoints: bleeding, diarrhea, pain, proctitis, sphincter control, and stricture. Lyman-Kutcher-Burman models with or without equivalent dose in 2 Gy/Fr correction were log-likelihood fitted by endpoint, estimating α/β ratios. The α/β ratio estimate sensitivity was assessed using sequential inclusion of dose modifying factors (DMFs): age, diabetes, hypertension, inflammatory bowel or diverticular disease (IBD/diverticular), and hemorrhoids. 95% confidence intervals (CIs) were bootstrapped. Likelihood ratio testing of 632 estimator log-likelihoods compared the models. RESULTS: Late rectal α/β ratio estimates (without DMF) ranged from bleeding (G1 + α/β = 1.6 Gy; 95% CI, 0.9-2.5 Gy) to sphincter control (G1 + α/β = 3.1 Gy; 95% CI, 1.4-9.1 Gy). Bowel pain modelled poorly (α/β, 3.6 Gy; 95% CI, 0.0-840 Gy). Inclusion of IBD/diverticular disease as a DMF significantly improved fits for stool frequency G2+ (P = .00041) and proctitis G1+ (P = .00046). However, the α/β ratios were similar in these no-DMF versus DMF models for both stool frequency G2+ (α/β 2.7 Gy vs 2.5 Gy) and proctitis G1+ (α/β 2.7 Gy vs 2.6 Gy). Frequency-weighted averaging of endpoint α/β ratios produced: G1 + α/β ratio = 2.4 Gy; G2 + α/β ratio = 2.3 Gy. CONCLUSIONS: We estimated α/β ratios for several common late adverse effects of rectal radiation therapy. When comparing dose-fractionation schedules, we suggest using late a rectal α/β ratio ≤ 3 Gy. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER SCIENCE INC | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | CHHiP Trial Management Group | |
dc.title | Estimates of Alpha/Beta (α/β) Ratios for Individual Late Rectal Toxicity Endpoints: An Analysis of the CHHiP Trial. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-12-24 | |
rioxxterms.versionofrecord | 10.1016/j.ijrobp.2020.12.041 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2021-01-04 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | International journal of radiation oncology, biology, physics | |
pubs.notes | No embargo | |
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/ICR-CTSU Urology and Head and Neck Trials Team | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams/Clinical Academic Radiotherapy (Dearnaley) | |
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.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/ICR-CTSU Urology and Head and Neck Trials Team | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams/Clinical Academic Radiotherapy (Dearnaley) | |
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 | Published | |
pubs.embargo.terms | No embargo | |
icr.researchteam | ICR-CTSU Urology and Head and Neck Trials Team | |
icr.researchteam | Clinical Academic Radiotherapy (Dearnaley) | |
icr.researchteam | Stereotactic and Precision Body Radiotherapy | |
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 | |