Inverse radiotherapy planning based on bioeffect modelling for locally advanced left-sided breast cancer

Abstract

Background and purpose: Treatment planning of radiotherapy (RT) for left-sided breast cancer is a challenging case. Several competing concerns are incorporated at present through protocol-defined dose-volume constraints, e.g. cardiac exposure and target coverage. Such constraints are limited by neglecting patient-specific risk factors (RFs). We propose an alternative RT planning method based solely on bioeffect models to minimize the estimated risks of breast cancer recurrence (BCR) and radiation-induced mortality endpoints considering patient-specific factors.

Methods and materials: Thirty-nine patients with left-sided breast cancer treated with comprehensive post-lumpectomy loco-regional conformal RT were included. An in-house particle swarm optimization (PSO) engine was used to choose fields from a large set of predefined fields and optimize monitor units to minimize the total risk of BCR and mortality caused by radiation-induced ischaemic heart disease (IHD), secondary lung cancer (SLC) and secondary breast cancer (SBC). Risk models included patient age, smoking status and cardiac risk and were developed using published multi-institutional data.

Results: For the clinical plans the normal tissue complication probability, i.e. summed risk of IHD, SLC and SBC, was <3.7% and the risk of BCR was <6.1% for all patients. Median total decrease in mortality or recurrence achieved with individualized PSO plans was 0.4% (range, 0.06-2.0%)/0.5% (range, 0.11-2.2%) without/with risk factors.

Conclusions: Inverse RT plan optimization using bioeffect probability models allows individualization according to patient-specific risk factors. The modelled benefit when compared to clinical plans is, however, modest in most patients, demonstrating that current clinical plans are close to optimal. Larger gains may be achievable with morbidity endpoints rather than mortality.

Keywords: Breast cancer; Optimization; Outcome modelling; Treatment planning.

Figure 1.

Example of field setup with tangential and supraclavicular fields: clinical field setup (a) and multifield setup (b).

Figure 2.

All plots show mean dose for individualized PSO plans for 0 RFs (x-axis) and ≥1 RFs (y-axis). Dose is moved away from lung and heart in patients with risk factors. Dose to IMN and primary CTV (whole breast + supraclavicular and axillary lymph nodes) is in most cases compromised more in patients with RFs. Abbreviations: RF, risk factor; MHD, mean heart dose; MLD, mean lung dose; MBD, mean breast dose; IMN, internal mammary nodes; CTV, clinical target volume.

Figure 3.

Dose-volume histogram for 1 patient comparing the PSO plan with no RFs (dashed lines), the PSO plan with 1 or more RFs (solid lines) and the clinical plan (dotted lines). The reduction in total risk (BCR + NTCP) relative to the clinical plan was 1.8% for both RF scenarios. Abbreviations: PSO, particle swarm optimization; BCR, breast cancer recurrence; NTCP, normal tissue complication probability; RF, risk factor; IMN, internal mammary nodes; CTV, clinical target volume.

Figure 4.

Risk of IHD (left panels) and SLC (right panels) for clinical plans (x-axis) vs PSO plans (y-axis). Upper panels show risk estimates assuming no risk factors and lower panels show risk estimates assuming 1 or more risk factors. Abbreviations: IHD, Ischemic heart disease; SLC, secondary lung cancer.

Figure 5.

Change in BCR (x-axis) vs total change in NTCP (y-axis) for clinical vs. PSO plans with no risk factors (upper panel) and at least 1 risk factor (lower panel). Change in BCR is defined as the risk estimate of BCR from the clinical plan minus the risk estimate of BCR from the individualized PSO plan. Total change in NTCP is defined as the risk estimate of NTCP from the clinical plan minus the risk estimate of NTCP from the individualized PSO plan. This implies that a negative change in risk of BCR and NTCP is an improvement relative to the clinical plan. Abbreviations: PSO, particle swarm optimization; BCR, breast cancer recurrence; NTCP, normal tissue complication probability.