Reducing heart dose without compromising target coverage in breastcancer radiotherapy: towards individualized treatment modality selection

Breast cancer has the highest incidence in women. Breast cancer treatment consists of a multimodality approach: surgery, adjuvant systemic treatment, adjuvant radiotherapy. Breast cancer patients have a relative good prognosis which is improving thanks to the increasing use of (cardiotoxic) systemic therapy and the technological developments.Adjuvant radiotherapy is performed with high-energy ionizing beams. Irradiation of the whole breast has a clear contribution to the good prognosis. However, it might also induce breast fibrosis with inferior cosmetic result in the long-term. Evidence-based data support the additional irradiation ofthe regional lymph nodes for high-risk patients. The disadvantage of radiotherapy is the unavoidable irradiation of the healthy tissue surrounding the target volumes e.g. the heart. Evidence-based data show that therisk of radiation-induced cardiac toxicity will increase in the future.The aim of this dissertation was therefore to investigate how to reducethe heart irradiation without compromising the target coverage.During treatment preparation a model of the patient is created using a CT-scan of the patient. The dose delivered to the target volumes and the organs-at-risk, e.g. the heart, is predicted by a dose calculation algorithm. Due to the complexity of the modeling of the interaction of the ionizing beams with the patient, different dose calculation algorithms exist. The impact of the dose calculation algorithm on the parameters of different radiobiological models was investigated. Those radiobiological models estimate the probability of tumor control or the probability of normaltissue complication. For the most advanced and most accurate dose calculation algorithms, new parameters were derived such that the clinical implementation of the new algorithm does not affect the probability of tumor control and the probability of breast fibrosis.The therapeutic dose is delivered in 16 or 25 daily fractions to enable the repair of sublethal damage in the organs-at-risk e.g. the heart. Therefore, the patient has to be positioned in the same position each day. Setup uncertainties are however unavoidable. To minimize the underdosage of the target volumes, margins are created around the target volume. Those margins definevolumes in which the target volume can move without deteriorating the target coverage. Large volumes ensure correct target coverage but increase the heart dose in left-sided breast radiotherapy. Small margins restrict the heart dose, but might induce target underdosage. Current linear accelerators are equipped with imaging technology enabling pre-treatment patient setup verification. In this dissertation a new and accurate technique for online setup verification was developed. The technique was used to determine the systematic setup error, i.e. the setup error occurring each day, and the random setup error, i.e. the error varying from day to day. Both errors were used to calculate the margins required in breast radiotherapy. Daily application of online setup verification and correction supported reducing those margins. It was shown that this induces areduction of the heart dose which is radiobiologically, i.e. clinically, significant. However, for a subgroup of the left-sided breast cancer patients, the heart dose remains unacceptably high. For those patients deep inspiration breath-hold breast radiotherapy can be applied. Irradiation is then restricted to the deep inspiration phase. Deep inspiration increases the distance between the breast and the heart and hence reduces the heart dose. This technique unavoidably increases the complexity of treatment preparation and treatment delivery. It is therefore of utmost importance to select those patients with clinical benefit at the beginning of the treatment preparation chain. In this dissertation a methodologyfor patient stratification between free-breathing and deep inspiration breath-hold breast radiotherapy was developed. The methodology has a high specificity.This dissertation proves that the integration of new and existing technologies in the treatment preparation chain reduces the heart dose without compromising the target coverage. The technologies incorporate accurate dose calculation algorithms and accurate setup verification and correction protocols. Individualized treatment modality selection improves workflow efficiency.status: publishe