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Background: Radiotherapy is a standard treatment option for breast cancer, but it may lead to significant late morbidity, including radiation heart damage. Breast irradiation performed individually in the supine or prone position may aid in minimizing the irradiation dose to the heart and LAD coronary artery. A series of CT scans and therapy plans are needed in both positions for the 'gold standard' decision on the preferable treatment position. This method is expensive with respect to technology and physician workload. Our ultimate goal is to develop a predictive tool to identify the preferable treatment position using easily measurable patient characteristics. In this article, we describe the details of how model building and consequently validation of the best model are done., Methods: Different models were used: both logistic regression and multiple linear regressions were used to estimate the LAD mean dose difference (the difference between the mean dose to the LAD in the supine position versus prone position); predicted dose differences were analysed compared to the 'gold standard' values, and the best model was selected accordingly. The final model was checked by random cross-validation. In addition to generally used measures (ROC and Brier score), decision curves were employed to evaluate the performance of the models., Results: ROC analysis demonstrated that none of the predictors alone was satisfactory. Multiple logistic regression models and the linear regression model lead to high values of net benefit for a wide range of threshold probabilities. Multiple linear regression seemed to be the most useful model. We also present the results of the random cross-validation for this model (i.e. sensitivity of 80.7% and specificity of 87.5%)., Conclusions: Decision curves proved to be useful to evaluate our models. Our results indicate that any of the models could be implemented in clinical practice, but the linear regression model is the most useful model to facilitate the radiation treatment decision. In addition, it is in use in everyday practice in the Department of Oncotherapy, University of Szeged, Hungary.

Background and Purpose: The benefit of reduced radiation heart exposure in the prone vs. supine position individually differs. In this prospective cohort study, the goal was to develop a simple method for the operation of a validated model for the prediction of preferable treatment position during left breast radiotherapy., Material and Methods: In 100 cases, a single CT slice was utilized for the collection of the needed patient-specific data (in addition to body mass index, the distance of the LAD from the chest wall and the area of the heart included in the radiation fields at the middle of the heart in the supine position). Outcome was analyzed in relation to the full CT series acquired in both positions and dosimetric data., Results: Great consistency was found between the tested and original method regarding sensitivity and specificity. The prioritization of LAD dose, and the use of heart dose and position-specific dose constraints as safety measures ensure sensitivity and specificity values of 82.8% and 87.3%, respectively. In an additional "routine clinical practice" series of 60 patients the new method seemed feasible in routine clinical practice. External testing on a 28-case series indicated similar accuracy., Conclusion: We consider this simple clinical tool appropriate for assisting individual positioning aiming at maximum heart protection during left breast irradiation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Prone positioning has been found feasible and appropriate for the reduction of radiation exposure of the lungs, but its effects on the heart dose remain controversial. Individual anatomical features were sought for the selection of optimal treatment positioning., Material and Methods: In 138 left-sided breast cancer cases awaiting postoperative whole-breast radiotherapy, conformal radiotherapy plans were generated in both prone and supine positions., Results: The radiation doses to the left anterior descending coronary artery (LAD) and heart in the two positions differed individually, and were strongly related to the body mass index (BMI). Image fusion of the CT scans revealed that prone positioning was detrimental if the heart was situated distant from the chest wall in the supine position, but moved to the chest wall in the prone position. For characterization of the geography of the heart and the breast, the median distance between the LAD and the chest wall (dmedian), and the heart area included in the radiation field on a single CT scan at the middle of the heart in the supine position (Aheart) proved most appropriate., Conclusion: A validated statistical model, utilizing the BMI, dmedian and Aheart, permits individualized positioning for maximum heart protection.

Purpose: To analyze the risk of radiogenic lung damage in breast cancer patients after conformal radiotherapy and different forms of systemic treatment., Methods and Materials: In 328 patients receiving sequential taxane-based chemotherapy, concomitant hormone therapy (tamoxifen or aromatase inhibitors), or no adjuvant systemic therapy, symptomatic and asymptomatic lung sequelae were prospectively evaluated via the detection of visible CT abnormalities, 3 months or 1 year after the completion of the radiotherapy., Results: Significant positive associations were detected between the development of both pneumonitis and fibrosis of Grade 1 and patient age, ipsilateral mean lung dose, volume of the ipsilateral lung receiving 20 Gy, and irradiation of the regional lymph nodes. In multivariate analysis, age and mean lung dose proved to be independent predictors of early (odds ratio [OR] = 1.035, 95% confidence interval [CI] 1.011-1.061 and OR = 1.113, 95% CI 1.049-1.181, respectively) and late (OR = 1.074, 95% CI 1.042-1.107 and OR = 1.207, 95% CI 1.124-1.295, respectively) radiogenic lung damage, whereas the role of systemic therapy was significant in the development of Grade 1 lung fibrosis (p = 0.01). Among the various forms of systemic therapy, tamoxifen increased the risk of late lung sequelae (OR = 2.442, 95% CI 1.120-5.326, p = 0.025). No interaction was demonstrated between the administration of systemic therapy and the other above-mentioned parameters as regards the risk of radiogenic lung damage., Conclusions: Our analyses demonstrate the independent role of concomitant tamoxifen therapy in the development of radiogenic lung fibrosis but do not suggest such an effect for the other modes of systemic treatment., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To study the risks of early and late radiogenic lung damage in breast cancer patients after conformal radiotherapy., Methods and Materials: Radiogenic lung sequelae were assessed prospectively in 119 patients by means of clinical signs, radiologic abnormalities, and the mean density change (MDC) of the irradiated lung on CT., Results: Significant positive associations were detected between the development of lung abnormalities 3 months or 1 year after the radiotherapy and the age of the patient, the ipsilateral mean lung dose (MLD), the radiation dose to 25% of the ipsilateral lung (D(25%)) and the volume of the ipsilateral lung receiving 20 Gy (V(20 Gy)). The irradiation of the axillary and supraclavicular lymph nodes favored the development of pneumonitis but not that of fibrosis. No relation was found between the preradiotherapy plasma TGF-beta level and the presence of radiogenic lung damage. At both time points, MDC was strongly related to age. Significant positive associations were demonstrated between the risks of pneumonitis or fibrosis and the age of the patient, MLD, D(25%), and V(20 Gy). A synergistic effect of MLD, D(25%), and V(20 Gy) with age in patients older than 59 years is suggested., Conclusion: Our analyses indicate that the risks of early and late radiogenic lung sequelae are strongly related to the age of the patient, the volume of the irradiated lung, and the dose to it.

Introduction: Radiotherapy comprises an integral part of the curative therapy of breast cancer by improving the locoregional control and survival when given on an individualized basis. Conformal radiotherapy and three-dimensional radiation treatment planning enhance the safety of radiotherapy by adjusting the irradiated volume to the shape of the target volume, and providing control of the radiation dose to the organs at risk (OARs)., Patients and Methods: The methods introduced at the authors' institute in 2002 are demonstrated. The breast/chest wall and lymph node areas were irradiated provided that there was a minimum risk of local or locoregional relapse of 10%. CT-based 3D radiotherapy treatment planning and individual patient-positioning were applied, with thermoplastic mask-fixation in the second part of the study. The dose constraints of the OARs were given in accordance with the literature recommendations. In the first group of patients, individually shaped blocks, in the second group, multileaf collimator, and in the third group, with the aim of a more homogenous dose-distribution in the target volume, intensity-modulated beams were applied., Results: During the study, 737 breast cancer patients received conformal radiotherapy based on individual risk estimation. In 372 cases only local, while in 365 cases locoregional radiotherapy was delivered. The dose-homogeneity in the target volume was significantly improved in the second period of the study, when segments were superposed on the radiotherapy fields. The proportions of the target volumes irradiated with +/-10% of the planned dose in the breast/chest wall, axillary and supraclavicular lymph nodes and internal mammary lymph nodes varied between 90.5-94.2%, 84.1-93.8% and 86.7-91.6%, respectively, depending on the radiation technique used. The parameters indicating the dose to the ipsilateral lung or to the heart were significantly higher when locoregional radiotherapy was applied compared to that in case of local radiotherapy. Radiation dose to the ipsilateral lung and the heart was significantly reduced in the second part of the study when locoregional, but not when local radiotherapy was delivered. The introduction of individual immobilization by means of thermoplastic mask-fixation resulted in a relevant decrease in the uncertainty due to breathing motion and daily positioning errors, and also in a significant reduction of the dose to the contralateral breast., Conclusions: Adjuvant radiotherapy should be based on individual risk-benefit features. The need of the introduction of special techniques may be decided after the dose-volume analysis of the conformal radiotherapy plan based on 3D radiation treatment planning.

Introduction: A retrospective analysis of the relation between the presence of casting-type calcifications on the mammogram and the prognosis of breast cancer was performed., Materials and Methods: The mammographic tumor features and other characteristics (invasive tumor size, histological tumor type, grade, nodal, hormone receptor and HER2 status, presence of lymphovascular invasion) of 55 high-risk breast cancers were studied., Results: After a median follow-up time of 29.1 months, the median relapse-free survival and overall survival times among breast cancer patients with tumors associated with casting calcifications were 26.6 and 29.6 months, respectively. The corresponding parameters among patients with tumors not accompanied by casting calcifications were 54.4 and > 58.5 months, respectively. Significant associations were found between the presence of casting calcifications and the risks of relapse (HR = 3.048, 95% CI: 1.116-8.323, p = 0.030) or death (HR = 3.504, 95% CI: 1.074-11.427, p = 0.038). Positive associations were found between casting calcifications and ER/PR negativity (p = 0.015 and p = 0.003, respectively) and HER2 overexpression (p = 0.019)., Discussion: Our findings support the theory that breast tumors associated with casting-type calcifications at mammography comprise a disease entity which exhibits significantly more aggressive behavior and a poorer outcome than do cancers with other mammographic tumor features.

Objective: The feasibility of dose-dense sequential adjuvant chemotherapy with Adriamycin, paclitaxel and cyclophosphamide was evaluated., Methods: Fifty-five high-risk breast cancer patients were enrolled. The following chemotherapy schedule was used: 4 x Adriamycin --> 4 x paclitaxel --> 4 x cyclophosphamide, q 2 weeks (Adriamycin, 60 mg/m2; paclitaxel, 200 mg/m2 over 3 h, and cyclophosphamide, 800 mg/m2)., Results: The dose intensity was 95.0, 99.8 and 97.4% of that planned for treatment with Adriamycin, paclitaxel and cyclophosphamide, respectively. During treatment with Adriamycin, paclitaxel and cyclophosphamide, 20, 12.7 and 25.5% of the patients, respectively, did not need filgrastim to maintain the dose density. The average number of filgrastim doses per cycle, when necessary, was 3.6. Neutropenia of grade 3-4 was found in 67.3, 13.5 and 10.0% of the patients after treatment with Adriamycin, paclitaxel and cyclophosphamide, respectively. A single case of febrile neutropenia was observed. Anemia occurred in 96.4% of the patients, and was significantly more frequent (p = 0.031) and more severe (p = 0.002) during paclitaxel treatment than in the other chemotherapy cycles., Conclusions: Dose-dense sequential chemotherapy with Adriamycin, paclitaxel and cyclophosphamide is well tolerated and safe. Individual treatment with granulocyte colony-stimulating factor is needed to maintain the dose density in most patients, but some tolerate this regimen without it, probably due to differences in drug clearances., ((c) 2005 S. Karger AG, Basel)