Estimates of Alpha/Beta (α/β) Ratios for Individual Late Rectal Toxicity Endpoints: An Analysis of the CHHiP Trial.

Adult Age Factors Aged Aged, 80 and over Anal Canal / physiopathology Diarrhea / complications Dose Fractionation, Radiation Gastrointestinal Hemorrhage / complications Humans Linear Models Male Middle Aged Organs at Risk / radiation effects Outcome Assessment, Health Care Probability Proctitis / complications Prostatic Neoplasms / radiotherapy Radiation Injuries / complications Radiation Tolerance Rectum / diagnostic imaging Urethral Stricture / complications

Journal

International journal of radiation oncology, biology, physics

ISSN: 1879-355X

Titre abrégé: Int J Radiat Oncol Biol Phys

Pays: United States

ID NLM: 7603616

Informations de publication

Date de publication:
01 06 2021

Historique:

received: 06 10 2020

revised: 10 12 2020

accepted: 24 12 2020

pubmed: 8 1 2021

medline: 27 8 2021

entrez: 7 1 2021

Statut: ppublish

Résumé

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. 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. 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. 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.

Identifiants

DOI: 10.1016/j.ijrobp.2020.12.041 PMID: 33412260 PMC: PMC8129972

pubmed: 33412260

pii: S0360-3016(20)34737-4

doi: 10.1016/j.ijrobp.2020.12.041

pmc: PMC8129972

pii:

doi:

Banques de données

ISRCTN

['ISRCTN97182923']

Types de publication

Clinical Trial, Phase III Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng