This study aims to identify key anatomic features that govern the individual variability of lung doses from breast-cancer radiotherapy. 3D conformal, intensity-modulated and hybrid techniques with 50.4 Gy whole-breast dose were planned for 128 patients. From their CT images, 17 anatomic measures were assessed and tested as predictors for lung dose-volume characteristics. Tangential techniques yielded mean ipsilateral lung doses in the range of 3-11 Gy. This inter-patient variability was explained to almost 40% by central lung distance, and to almost 60% if this measure was complemented by midplane lung width and maximum heart distance. Also the variability in further dose-volume metrics such as volume fractions receiving 5, 20 or 40 Gy could be largely explained by the anatomy. Multi-field intensity-modulated radiotherapy reduced high-exposed lung volumes, but resulted in higher mean ipsilateral lung doses and larger low-dose burden. Contralateral lung doses ranged from 0.3 to 1 Gy. The results highlight that there are large differences in lung doses among breast-cancer patients. Most of this inter-individual variability can be explained by a few anatomic features. The results will be implemented in a dedicated software tool to provide personalized estimates of long-term health risks related to breast-cancer radiotherapy. The results may also be used to identify favourable as well as problematic anatomies, and serve as a quick quantitative benchmark for individual treatment plans.

• MeSH
• konformní radioterapie * metody   MeSH
• lidé MeSH
• nádory prsu * radioterapie   MeSH
• plánování radioterapie pomocí počítače metody   MeSH
• plíce diagnostické zobrazování   MeSH
• prsy diagnostické zobrazování   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In breast cancer radiotherapy, substantial radiation exposure of organs other than the treated breast cannot be avoided, potentially inducing second primary cancer or heart disease. While distant organs and large parts of nearby ones receive doses in the mGy-Gy range, small parts of the heart, lung and bone marrow often receive doses as high as 50 Gy. Contemporary treatment planning allows for considerable flexibility in the distribution of this exposure. To optimise treatment with regards to long-term health risks, evidence-based risk estimates are required for the entire broad range of exposures. Here, we thus propose an approach that combines data from medical and epidemiological studies with different exposure conditions. Approximating cancer induction as a local process, we estimate organ cancer risks by integrating organ-specific dose-response relationships over the organ dose distributions. For highly exposed organ parts, specific high-dose risk models based on studies with medical exposure are applied. For organs or their parts receiving relatively low doses, established dose-response models based on radiation-epidemiological data are used. Joining the models in the intermediate dose range leads to a combined, in general non-linear, dose response supported by data over the whole relevant dose range. For heart diseases, a linear model consistent with high- and low-dose studies is presented. The resulting estimates of long-term health risks are largely compatible with rate ratios observed in randomised breast cancer radiotherapy trials. The risk models have been implemented in a software tool PASSOS that estimates long-term risks for individual breast cancer patients.

• MeSH
• hodnocení rizik MeSH
• kouření MeSH
• leukemie MeSH
• lidé MeSH
• nádory plic MeSH
• nádory prsu radioterapie   MeSH
• nemoci srdce MeSH
• software MeSH
• teoretické modely * MeSH
• vztah dávky záření a odpovědi MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Track structure based simulations valuably complement experimental research on biological effects of ionizing radiation. They provide information at the highest level of detail on initial DNA damage induced by diverse types of radiation. Simulations with the biophysical Monte Carlo code PARTRAC have been used for testing working hypotheses on radiation action mechanisms, for benchmarking other damage codes and as input for modelling subsequent biological processes. To facilitate such applications and in particular to enable extending the simulations to mixed radiation field conditions, we present analytical formulas that capture PARTRAC simulation results on DNA single- and double-strand breaks and their clusters induced in cells irradiated by ions ranging from hydrogen to neon at energies from 0.5 GeV/u down to their stopping. These functions offer a means by which radiation transport codes at the macroscopic scale could easily be extended to predict biological effects, exploiting a large database of results from micro-/nanoscale simulations, without having to deal with the coupling of spatial scales and running full track-structure calculations.

• MeSH
• dvouřetězcové zlomy DNA účinky záření   MeSH
• lidé MeSH
• lineární přenos energie MeSH
• metoda Monte Carlo * MeSH
• poškození DNA * MeSH
• protony * MeSH
• radioterapie * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The purpose of this study was to estimate the additional risk of side effects attributed to internal mammary node irradiation (IMNI) as part of regional lymph node irradiation (RNI) in breast cancer patients and to compare it with estimated overall survival (OS) benefit from IMNI. MATERIAL AND METHODS: Treatment plans (n = 80) with volumetric modulated arc therapy (VMAT) were calculated for 20 patients (4 plans per patient) with left-sided breast cancer from the prospective GATTUM trial in free breathing (FB) and in deep inspiration breath hold (DIBH). We assessed doses to organs at risk ((OARs) lung, contralateral breast and heart) during RNI with and without additional IMNI. Based on the OAR doses, the additional absolute risks of 10-year cardiac mortality, pneumonitis, and secondary lung and breast cancer were estimated using normal tissue complication probability (NTCP) and risk models assuming different age and risk levels. RESULTS: IMNI notably increased the mean OAR doses. The mean heart dose increased upon IMNI by 0.2-3.4 Gy (median: 1.9 Gy) in FB and 0.0-1.5 Gy (median 0.4 Gy) in DIBH. However, the estimated absolute additional 10-year cardiac mortality caused by IMNI was <0.5% for all patients studied except 70-year-old high risk patients (0.2-2.4% in FB and 0.0-1.1% in DIBH). In comparison to this, the published oncological benefit of IMNI ranges between 3.3% and 4.7%. The estimated additional 10-year risk of secondary cancer of the lung or contralateral breast ranged from 0-1.5% and 0-2.8%, respectively, depending on age and risk levels. IMNI increased the pneumonitis risk in all groups (0-2.2%). CONCLUSION: According to our analyses, the published oncological benefit of IMNI outweighs the estimated risk of cardiac mortality even in case of (e.g., cardiac) risk factors during VMAT. The estimated risk of secondary cancer or pneumonitis attributed to IMNI is low. DIBH reduces the estimated additional risk of IMNI even further and should be strongly considered especially in patients with a high baseline risk.

• MeSH
• celková dávka radioterapie * MeSH
• kritické orgány MeSH
• lidé MeSH
• nádory prsu radioterapie   MeSH
• nemoci srdce mortalita   MeSH
• plánování radioterapie pomocí počítače MeSH
• prospektivní studie MeSH
• radiační poranění mortalita   MeSH
• radioterapie škodlivé účinky   mortalita   MeSH
• senioři MeSH
• srdce účinky záření   MeSH
• zadržování dechu MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The biophysical simulation tool PARTRAC has been primarily developed to model radiation physics, chemistry and biology on nanometre to micrometre scales. However, the tool can be applied in simulating radiation effects in an event-by-event manner over macroscopic volumes as well. Benchmark simulations are reported showing that PARTRAC does reproduce the macroscopic Bragg peaks of proton beams, although the penetration depths are underestimated by a few per cent for high-energy beams. PARTRAC also quantifies the increase in DNA damage and its complexity along the beam penetration depth. Enhanced biological effectiveness is predicted in particular within distal Bragg peak parts of therapeutic proton beams.

• MeSH
• algoritmy MeSH
• DNA účinky záření   MeSH
• dvouřetězcové zlomy DNA účinky záření   MeSH
• lineární přenos energie MeSH
• metoda Monte Carlo MeSH
• počítačová simulace * MeSH
• poškození DNA MeSH
• protonová terapie MeSH
• protony MeSH
• relativní biologická účinnost MeSH
• software MeSH
• voda MeSH
• výpočetní biologie MeSH
• Publikační typ
• časopisecké články MeSH

Breast cancer radiotherapy may in the long term lead to radiation-induced secondary cancer or heart disease. These health risks hugely vary among patients, partially due to anatomy-driven differences in doses deposited to the heart, ipsilateral lung and contralateral breast. We identify four anatomic features that largely cover these dosimetric variations to enable personalized risk estimates. For three exemplary, very different risk scenarios, the given parameter set reproduces 63-74% of the individual risk variability for left-sided breast cancer patients. These anatomic features will be used in the PASSOS software to support decision processes in breast-cancer therapy.

• MeSH
• celková dávka radioterapie MeSH
• kritické orgány účinky záření   MeSH
• lidé MeSH
• nádory prsu radioterapie   MeSH
• nádory vyvolané zářením etiologie   patologie   MeSH
• plánování radioterapie pomocí počítače metody   MeSH
• plíce patologie   účinky záření   MeSH
• počítačová rentgenová tomografie metody   MeSH
• počítačové zpracování obrazu metody   MeSH
• prsy patologie   účinky záření   MeSH
• radiační poranění etiologie   patologie   MeSH
• radioterapie s modulovanou intenzitou škodlivé účinky   MeSH
• srdce anatomie a histologie   účinky záření   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH