Minimum breast distance largely explains individual variability in doses to contralateral breast from breast-cancer radiotherapy

 

Breast cancer is the most frequent cancer in women worldwide. Fortunately, its cure rates are high if diagnosed at an early stage. Commonly it is treated by breast-conserving surgery complemented by adjuvant whole-breast radiotherapy. Breast-cancer radiotherapy reduces local recurrence and mortality rates. However, in the long term it also increases the incidence of secondary cancers, in particular in the lungs and contralateral breast, and the mortality through heart disease, mainly for patients with left-sided breast tumours. The benefits of radiotherapy clearly outweigh its risks. Nevertheless, as the cure rates get improved and patient survival prolonged, these long-term health risks become increasingly important.

The radiation risks hugely vary among individual patients. They are affected by age, smoking and other lifestyle factors, and by genetic background. The risks depend on doses to which diverse organs are exposed. In particular, exposures of the heart, ipsilateral lung, and contralateral breast are linked with relatively high risk. The organ doses vary in dependence on patient anatomy. Maximum heart distance and central lung distance, defined as the extent of the respective organ that would be covered by a tangential field, serve as useful anatomic measures that largely correlate with mean doses to the heart and lung. However, no such measure has been defined so far that would be linked with the variability of doses to the contralateral breast.

In the PASSOS project, treatment-planning data were gathered for 128 early-stage breast cancer patients in two radiotherapy centres. Contralateral breast doses in individual patients ranged from 0.2 to 1.6 Gy for 3D conformal radiotherapy without wedges. The application of wedges increased contralateral breast doses by 0.2 – 0.4 Gy, while flattening filter-free irradiations reduced them by 0.1 – 0.2 Gy. Intensity modulated radiotherapy led to contralateral breast doses of 1 – 7 Gy.

To explain the individual variability in contralateral breast doses, numerous anatomic features were assessed from the patients’ CT images and tested as dose predictors by fitting the treatment planning data. Minimum breast distance, defined in analogy to the above-mentioned measures as the distance of the contralateral breast from the tangential field, was identified as an anatomic feature highly correlated with contralateral breast doses, explaining about 60% of their variability. Contralateral breast doses exponentially decrease with increasing minimum breast distance, by about 10 – 15% per 1 cm increase in this measure. Also further dose-volume metrics such as dose to the most exposed 1% of the organ or its fraction receiving 0.5 Gy dose are linked to the minimum breast distance.

Fig 1: Individual variability in contralateral breast doses is largely covered by minimum breast distance. Shown is the model fit (line) to mean contralateral breast doses from flattening filter-free whole-breast irradiations for 78 early-stage breast-cancer patients treated at the Clinic of Radiation therapy and Radiation Oncology, University Leipzig (squares).

These personalized estimates of contralateral breast doses may help improve retrospective analyses of data on long-term health risks from radiation therapy. The estimates may also be helpful in centres where contouring and/or dosimetry of this organ is not routinely performed. Most importantly, the personalized estimates may be used for patient stratification and for efficient application of techniques that spare the contralateral breast.

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Publication:
Kundrát P et al. Minimum breast distance largely explains individual variability in doses to contralateral breast from breast-cancer radiotherapy. Radiother Oncol (2018), doi.org/10.1016/j.radonc.2018.08.022

Kundrát P, Remmele J, Rennau H, Sebb S, Simonetto C, Eidemüller M, Wolf U, Hildebrandt G. Inter-Patient variability in doses to nearby organs in breast-cancer radiotherapy: Inference from anatomic features. Radiat Prot Dosimetry. 2019;183(1-2):255-258