External validation of survival of lung cancer patients due to setup uncertainties towards the heart
Brink, C. Bernchou, U. Bertelsen, A. Hansen, O. Schytte, T. Holloway, L. Van Herk, Marcel Johnson-Hart, Corinne Price, Gareth J Aznar, Marianne Camille
Brink, C.
Bernchou, U.
Bertelsen, A.
Hansen, O.
Schytte, T.
Holloway, L.
Van Herk, Marcel
Johnson-Hart, Corinne
Price, Gareth J
Aznar, Marianne Camille
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Abstract
Purpose or Objective
The impact on survival due to heart toxicity for lung cancer
patients treated with radiotherapy (RT) has been difficult
to quantify, due to correlations between dose to heart and
lung with tumor burden. A possible measure that indicates
enhanced dose to heart but does not correlate with the
other risk factors is the deviation between actual and
planned daily distance between isocenter and heart. The
average of this daily distance (DeltaD), which can be
obtained from CBCT scans, will for positive values indicate
larger separation of target and heart and thus reduced
heart dose during delivery. DeltaD has previously been
reported to impact survival [Johnson-Hart et al IJROBP
2018]. The aim of the current study is to undertake an
external validation of this finding in another institution
Material and Methods
All patients treated in the validation department from
April 2010 to end 2015 with daily CBCT, planned dose of
60-66 Gy in 2 Gy fractions and for which a heart delineation
was available were collected for analysis. Standard clinical
IGRT procedure utilized two registrations for each CBCT 1)
tumor region (mask) and 2) overall anatomy (clipbox). The
first was used for patient positioning while the latter was
used for overall validation of the anatomy. The latter is
representative of the heart position, while the first
represents the tumor position hence the treatment
isocenter. The difference between the registrations can
thus be used to estimate the daily shift of the heart
relative to the isocenter. Based on clinical data
(performance status, GTV volume, Age, T and N stage,
histology, tumor stage and dose) a base Cox model
predicting survival was created using Lasso for parameter
selection. Impact of continuous variable DeltaD was tested
by adding DeltaD to the base Cox model. All analyses were
performed in R v. 3.6.1.
Results
300 patients were included. DeltaD did not correlate
statistically significant with any of the clinical factors. Range of DeltaD was -0.6 cm to 0.7 cm. Figure 1 shows
Kaplan-Meier plots of patients with positive versus
negative DeltaD. It is seen that a split of the curves occurs
around 16 months after the start of RT. The base Cox
model included performance status, ln(GTV volume) and
Age. DeltaD was included in the base model using time
dependent Cox regression for which DeltaD effectively was
zero until 16 months after RT. This resulted in a statistically significant regression constant of DeltaD of -
1.63 per cm (HR=0.195) with p-value of 0.017
Conclusion As in the original study this validation study demonstrates
significant impact on survival due to estimated setup
errors in the direction of the heart, even with daily online
IGRT corrections. This indicates that dose to heart impacts
survival for these patients. However, in contrast to the
original study the effect of DeltaD only starts 16 months
after RT. This difference in the two studies might reflect
differences in treatment or patient cohorts at the two
centers, and calls for additional external validation.
Description
Date
2020
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Brink C, Bernchou U, Bertelsen A, Hansen O, Schytte T, Holloway L, et al. PH-0650: External validation of survival of lung cancer patients due to setup uncertainties towards the heart. Radiotherapy and Oncology . 2020 Nov;152:S360–1.