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Estimation of the α/β ratio of non-small cell lung cancer treated with stereotactic body radiotherapy


Abstract

Background

High-dose hypofractionated radiotherapy should theoretically result in a deviation from the typical linear-quadratic shape of the cell survival curve beyond a certain threshold dose, yet no evidence for this hypothesis has so far been found in clinical data of stereotactic body radiotherapy treatment (SBRT) for early-stage non-small cell lung cancer (NSCLC). A pragmatic explanation is a larger α/β ratio than the conventionally assumed 10 Gy. We here attempted an estimation of the α/β ratio for NSCLC treated with SBRT using individual patient data.
Materials and methods

We combined two large retrospective datasets, yielding 1294 SBRTs (≤10 fractions) of early stage NSCLC. Cox proportional hazards regression, a logistic tumor control probability model and a biologically motivated Bayesian cure rate model were used to estimate the α/β ratio based on the observed number of local recurrences and accounting for tumor size.
Results

A total of 109 local progressions were observed after a median of 17.7 months (range 0.6–76.3 months). Cox regression, logistic regression of 3 year tumor control probability and the cure rate model yielded best-fit estimates of α/β = 12.8 Gy, 14.9 Gy and 12–16 Gy (depending on the prior for α/β), respectively, although with large uncertainties that did not rule out the conventional α/β = 10 Gy.
Conclusions

Clinicians can continue to use the simple LQ formalism to compare different SBRT treatment schedules for NSCLC. While α/β = 10 Gy is not ruled out by our data, larger values in the range 12–16 Gy are more probable, consistent with recent meta-regression analyses.

Abstract

Background

High-dose hypofractionated radiotherapy should theoretically result in a deviation from the typical linear-quadratic shape of the cell survival curve beyond a certain threshold dose, yet no evidence for this hypothesis has so far been found in clinical data of stereotactic body radiotherapy treatment (SBRT) for early-stage non-small cell lung cancer (NSCLC). A pragmatic explanation is a larger α/β ratio than the conventionally assumed 10 Gy. We here attempted an estimation of the α/β ratio for NSCLC treated with SBRT using individual patient data.
Materials and methods

We combined two large retrospective datasets, yielding 1294 SBRTs (≤10 fractions) of early stage NSCLC. Cox proportional hazards regression, a logistic tumor control probability model and a biologically motivated Bayesian cure rate model were used to estimate the α/β ratio based on the observed number of local recurrences and accounting for tumor size.
Results

A total of 109 local progressions were observed after a median of 17.7 months (range 0.6–76.3 months). Cox regression, logistic regression of 3 year tumor control probability and the cure rate model yielded best-fit estimates of α/β = 12.8 Gy, 14.9 Gy and 12–16 Gy (depending on the prior for α/β), respectively, although with large uncertainties that did not rule out the conventional α/β = 10 Gy.
Conclusions

Clinicians can continue to use the simple LQ formalism to compare different SBRT treatment schedules for NSCLC. While α/β = 10 Gy is not ruled out by our data, larger values in the range 12–16 Gy are more probable, consistent with recent meta-regression analyses.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Radiation Oncology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Hematology
Health Sciences > Oncology
Health Sciences > Radiology, Nuclear Medicine and Imaging
Uncontrolled Keywords:Oncology, Radiology Nuclear Medicine and imaging, Hematology
Language:English
Date:2020
Deposited On:04 Feb 2020 17:54
Last Modified:29 Jul 2020 13:21
Publisher:Elsevier
ISSN:0167-8140
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.radonc.2019.07.008
PubMed ID:31431371

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