Peritumoural density as a biomarker of distant failure in NSCLC patients treated with SABR
Davey, Angela Van Herk, Marcel Faivre-Finn, Corinne Brown, S McWilliam, Alan
Davey, Angela
Van Herk, Marcel
Faivre-Finn, Corinne
Brown, S
McWilliam, Alan
Citations
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Abstract
Purpose or Objective
Predictors of distant failure (DF) have not been established
for NSCLC patients treated with SABR. Image markers have
been proposed describing potential risk of microscopic
disease extension (MDE), stratifying patients with locoregional
failure on dose to surrounding tissue (Salguero,
2013). In this work, we propose peritumoural density to
describe MDE and risk of metastatic disease. We
investigate peritumoural density taking dose variability
into account.
Material and Methods
An in-house validated technique generated the GTV on the
50% 4DCT phase for 259 patients treated with SABR in 3, 5
or 8 fractions. Dose was converted to EQD2 with α/β=10.
Local rigid registration was used to match tumour in each
phase to 50% and calculate respiratory motion. Dose
distribution was blurred according to respiratory motion to
estimate delivered dose.
In-house data-mining was used to sample CT pixel values
(inside lung) and dose at radial distance from the GTV.
Briefly, we calculated the signed distance transform and
created 2D cross-histograms of pixel value/dose versus
distance for each patient. For every 1mm, dose standard
deviation (SD) and mean pixel value was sampled Average cross-histograms of mean pixel value were
calculated for patients who did and did not experience DF
at 18 months, censored for follow-up. T-statistic
describing difference in cross-histograms defined an
important region, using permutation testing for statistical
significance. Mean pixel value was sampled from this
region.
Dose variability (SD) was sampled from the region (Fig.1A)
extending outside the PTV, but within the expected MDE
range (5-15mm), where high SD represents higher chance
of underdosing MDE.
Patients were split into low and high dose variability based
on the median. For each cohort, mean pixel value was
assessed in univariable and multivariable Cox regression.
Results
The region of greatest density difference was identified as
-3mm to 7mm (Fig.1B). On univariable analysis, there was
no association with DF for mean pixel value or dose SD
alone. Median dose SD was 8.4Gy. However, higher pixel value predicts DF for high dose
variability (HR=1.76, p=0.014), but not when dose is
uniform (HR=1.12, p=0.665). This is true for continuous
pixel value and split on the median (Fig.2A). HR for
continuous pixel value represents increase in hazard per
100HU. This association remained in multivariable analysis
correcting for tumour volume (Fig.2B). Mean pixel value
and dose SD do not correlate with clinical variables.
Conclusion
High peritumoural density is prognostic for DF when
surrounding dose is not uniform. Peritumoural density
correlates with published biomarker GTV surface density,
however, a larger region is sampled. The larger region may
be less sensitive to observer variation, and capture
information on tumour invasiveness which is likely
important for risk of metastatic disease. Tumours with a
high peritumoural density could benefit from increased
margins. We aim to validate this work in an external
cohort.
Description
Date
2020
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Davey A, Van Herk M, Faivre-Finn C, Brown S, McWilliam A. OC-0096: Peritumoural density as a biomarker of distant failure in NSCLC patients treated with SABR. Radiotherapy and Oncology . 2020 Nov;152:S44–5.