Reducing the Risk of Secondary Lung Cancer in Treatment Planning of Accelerated Partial Breast Irradiation

Nienke Hoekstra, Steven Habraken, Annemarie Swaak-Kragten, Sebastiaan Breedveld, Jean-Philippe Pignol, Mischa Hoogeman, Nienke Hoekstra, Steven Habraken, Annemarie Swaak-Kragten, Sebastiaan Breedveld, Jean-Philippe Pignol, Mischa Hoogeman

Abstract

Purpose: Adjuvant accelerated partial breast irradiation (APBI) results in low local recurrence risks. However, the survival benefit of adjuvant radiotherapy APBI for low-risk breast cancer might partially be offset by the risk of radiation-induced lung cancer. Reducing the lung dose mitigates this risk, but this could result in higher doses to the ipsilateral breast. Different external beam APBI techniques are equally conformal and homogenous, but the intermediate to low dose distribution differs. Thus, the risk of toxicity is different. The purpose of this study is to quantify the trade-off between secondary lung cancer risk and breast dose in treatment planning and to compare an optimal coplanar and non-coplanar technique. Methods: A total of 440 APBI treatment plans were generated using automated treatment planning for a coplanar VMAT beam-setup and a non-coplanar robotic stereotactic radiotherapy beam-setup. This enabled an unbiased comparison of two times 11 Pareto-optimal plans for 20 patients, gradually shifting priority from maximum lung sparing to maximum ipsilateral breast sparing. The excess absolute risks of developing lung cancer and breast fibrosis were calculated using the Schneider model for lung cancer and the Avanzo model for breast fibrosis. Results: Prioritizing lung sparing reduced the mean lung dose from 2.2 Gy to as low as 0.3 Gy for the non-coplanar technique and from 1.9 Gy to 0.4 Gy for the coplanar technique, corresponding to a 7- and 4-fold median reduction of secondary lung cancer risk, respectively, compared to prioritizing breast sparing. The increase in breast dose resulted in a negligible 0.4% increase in fibrosis risk. The use of non-coplanar beams resulted in lower secondary cancer and fibrosis risks (p < 0.001). Lung sparing also reduced the mean heart dose for both techniques. Conclusions: The risk of secondary lung cancer of external beam APBI can be dramatically reduced by prioritizing lung sparing during treatment planning. The associated increase in breast dose did not lead to a relevant increase in fibrosis risk. The use of non-coplanar beams systematically resulted in the lowest risks of secondary lung cancer and fibrosis. Prioritizing lung sparing during treatment planning could increase the overall survival of early-stage breast cancer patients by reducing mortality due to secondary lung cancer and cardiovascular toxicity.

Keywords: accelerated partial breast irradiation; breast cancer; plan optimization; radiotherapy techniques; secondary lung cancer.

Copyright © 2020 Hoekstra, Habraken, Swaak-Kragten, Breedveld, Pignol and Hoogeman.

Figures

Figure 1
Figure 1
Dose distributions for an example case. The dose distributions on the left show coplanar VMAT plans, on the right non-coplanar CyberKnife (CK) plans. The upper dose distributions are plans with maximum priority to sparing of the breast tissue, and the lower dose distributions are plans with maximum sparing of the lungs. The middle dose distributions are plans with equal priorities to the sparing of lung and breast tissue.
Figure 2
Figure 2
Average DVHs for the different treatment plans. Coplanar VMAT plans are shown in (A), non-coplanar CyberKnife (CK) plans are shown in (B). The solid lines show the results for the plan that fully prioritizes lung sparing. The dashed lines show the result of the treatment plan that fully prioritizes breast sparing.
Figure 3
Figure 3
Pareto fronts for individual patients of the mean doses to the ipsilateral breast and lungs. Non-coplanar CyberKnife (CK) plans are shown in blue circles, coplanar VMAT plans are shown in red squares. The thick lines show the average over all patients per technique.
Figure 4
Figure 4
Scatterplots of the maximum breast sparing plans vs. the maximum lung sparing plans. (A) shows the secondary lung cancer risk, (B) the breast fibrosis risk, and (C) the mean heart dose. Non-coplanar CyberKnife (CK) plans are shown in blue circles, coplanar VMAT plans are shown in red squares. Data points below the unity line indicate an advantage for the dose plan on the vertical axis.

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