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Aim: To analyse the use of radiotherapy (RT) and factors affecting overall survival (OS) after RT in breast cancer patients with brain metastases., Methods: Breast cancer patients treated from 2008 to 2018 with whole brain RT (WBRT) or stereotactic radiosurgery (SRS) at a large regional cancer referral center were identified from the hospital's RT register. Clinical variables were extracted from medical records. OS was calculated from date of first RT until death or last follow up. Potential factors affecting OS were analyzed., Results: 255 females with WBRT (n = 206) or SRS (n = 49) as first RT were included. An increased use of initial SRS was observed in the second half of the study period. The most common WBRT fractionation regimen was 3 Gy × 10. SRS was most often single fractions; 18 or 25 Gy between 2009 and 2016, while fractionated SRS was mostly used in 2017 and 2018. Median OS in the WBRT group was 6 months (CI 1-73) relative to 23 (CI 0-78) in the SRS group. Age, performance status, initial RT technique, extracranial disease, brain metastasis surgery, number of brain metastases and DS-GPA score had significant impact on OS. Only ECOG 0 and brain metastasis surgery were associated with superior OS in multivariate analysis., Conclusion: WBRT was the most frequent primary RT. An increased use of initial SRS was observed in the second half of the study period. Only ECOG 0 and brain metastasis surgery were associated with superior OS in multivariate analysis., (Copyright © 2021. Published by Elsevier Inc.)

Background/purpose: We explored the relation between coronary artery calcium (CAC) and cardiac radiation doses in breast cancer survivors (BCS) treated with radiotherapy (RT). Additionally, we examined the impact of other risk factors and biomarkers of coronary artery disease (CAD)., Materials and Methods: 236 BCS (median age 51years [range 30-70], median observation time 12years [9.2-15.7]), treated with 4-field RT of 50GY, were included and examined in 2004 (T1), 2007 (T2) and 2011 (T3) with clinical examination, blood tests and questionnaires. At T3, cardiac computed tomography was performed with quantification of CAC using Agatston score (AS). For 106 patients cardiac dose volume histograms were available., Results: The cohort-based median of the mean cardiac dose was 2.5 (range 0.5-7.0) Gy. There was no correlation between measures of cardiac dose and AS. AS was correlated with high cholesterol at T1/T2 (p=0.022), high proBNP at T1/T2 (p<0.022) and T3 (p<0.022) and high HbA1c at T3 (p=0.022). In addition, a high AS was significantly associated with hypertension (p=0.022). Age (p<0.001) and cholesterol at T1/T2 (p=0.001) retained significant associations in multivariate analysis., Conclusions: Traditional, modifiable risk factors of CAD correlate with CAC and may be important for the long term risk of CAD after RT. With low to moderate cardiac radiation exposure, a contribution of radiation dose to CAC could not be demonstrated., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To explore the relationship between radiotherapy (RT) dose levels in the arm/shoulder region and arm/shoulder morbidity in breast cancer patients., Material and Methods: This study included 183 breast cancer patients who had received locoregional RT with or without chemotherapy and/or hormone treatment during the period 1998-2002. Individual RT dose level, reflected by dose-volume histograms (DVHs), for the shoulder joint and joining structures were obtained from archived CT-based RT plans. Individual median, mean and maximum arm/shoulder RT dose levels were extracted. Arm/shoulder morbidity was assessed 29-58 months after breast cancer treatment using the following clinical endpoints: arm pain, arm stiffness, swollen arm, use of arm, numbness, shoulder flexion and shoulder abduction difference, fibrosis and breast cancer-related lymphedema. The relationship between arm/shoulder RT dose level and these clinical endpoints was assessed by Spearman's correlation and multivariate logistic regression., Results: Ninety-one percent of the included patients had some degree of arm/shoulder morbidity. Neither mean nor maximum RT dose level was associated with clinical endpoints. However, significant correlations (p < 0.05) were found between DVHs and arm stiffness, arm pain, use of arm and shoulder abduction difference, when arm/shoulder RT dose levels were approximately 15 Gy., Conclusions: Three-dimensional conformal locoregional RT for breast cancer results in long-term arm/shoulder morbidity. To minimize this risk, large shoulder volumes receiving RT doses of approximately 15 Gy should be reduced.

Purpose: To explore very-long-term mortality from ischemic heart disease (IHD) after locoregional radiation therapy of breast cancer (BC) in relation to degree of hypofractionation and other treatment variables., Methods and Materials: Two hypofractionated regimens used for locoregional radiation therapy for BC from 1975 to 1991 were considered. Patients received 4.3 Gy × 2/week (10 fractions; target dose 43 Gy; n=1107) or 2.5 Gy × 5/week (20 fractions; target dose 50 Gy; n=459). To estimate cardiac doses, radiation fields were reconstructed in a planning system. Time to death from IHD was the endpoint, comparing the groups with each other and with age-matched, cancer-free control individuals, modeled with the Cox proportional hazards model., Results: Patients given 4.3 Gy × 10 had an increased risk of dying of IHD compared with both the 2.5 Gy group (hazard ratio [HR] = 2.37; 95% confidence interval [CI]: 1.06-5.32; P=.036) and the control group (HR = 1.59; 95% CI: 1.13-2.23; P=.008). Photon beams for parasternal fields gave an increased risk of dying of IHD compared with electron beams (HR = 2.56; 95% CI: 1.12-5.84; P=.025). Multivariate analysis gave an increased risk for the 4.3-Gy versus 2.5-Gy regimen with borderline significance (HR = 2.90; 95% CI: 0.97-8.79; P=.057) but not for parasternal irradiation., Conclusions: The degree of hypofractionation and parasternal photon beams contributed to increased cardiac mortality in this patient cohort. Differences emerged after 12 to 15 years, indicating the need of more studies with observation time of 2 decades., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To assess the impact of using breathing adapted radiotherapy on contralateral breast (CB) dose, to relate the thorax shape with the dose to the organs at risk (OARs) and to predict the risk for induced malignancies in CB using linear and non-linear models, following tangential irradiation of breast., Material and Methods: Sixteen patients with stage I-II breast cancer treatment planned with tangential fields using deep inspiration breath hold (DIBH) and free breathing (FB) techniques were included in this analysis. The dose results mainly based on DVH analysis were compared. Four parameters were defined to describe thoracic shape. Excess relative risk (ERR) for cancer induction in CB, employing linear and non-linear models was calculated., Results: Average CB volumes exposed to a dose of 1 Gy is 1.3 times higher in DIBH plans than in FB plans. No significant difference in average V3Gy and V5Gy for DIBH and FB plans is observed. The average mean CB dose for DIBH and FB plans is 0.33 and 0.28 Gy, respectively. No correlation between thorax shape parameters and mean OARs dose is observed. The estimated average mean ERR with linear model is lower in FB plans (0.12) than for the DIBH plans (0.14). The estimated ERR with non-linear model is 0.14 for DIBH plans and 0.15 for FB plans., Conclusion: No significant difference in CB dose between DIBH and FB plans is observed. The four thorax shape parameters defined in this study can not be related to the dose at OARs using DIBH and FB radiation techniques. The ERR estimates for secondary CB cancer are nearly the same for FB and DIBH planning when using a linear and non-linear risk prediction models.

Purpose: To investigate the impact of using different radiation therapy techniques on contra-lateral breast (CB) dose, and also dose to other involved organs at risk such as heart and lungs following radiation therapy of breast and regional lymph nodes. Furthermore, to predict the risk for induced malignancies in CB using linear and non linear models., Material and Methods: Eight patients with stage II-III breast cancer were included in this analysis. It was focused on three treatment techniques; conventional radiotherapy technique forwardly planed, IMRT and volumetric modulated arc (RapidArc) techniques, inversely planed. The CC algorithm was employed to calculate the standard treatment plans whereas for the IMRT and RapidArc treatment plans AAA algorithm was adopted. The dose results based on mostly DVH analysis were compared. The excess relative risk (ERR) for cancer induction in CB, employed both linear and non-linear models, was estimated., Results: A better homogeneity and conformation in PTV was observed in the RapidArc plans. The highest minimum dose to PTV was observed in the conventional plans while no difference was observed for minimum significant doses D(98%) and D(99%) where D(X%) is the dose received by X% of the PTV volume. In terms of organ sparing, the IMRT and RapidArc plans spare ipsilateral-lung better, but a 40% lower mean dose in the contra-lateral lung in the conventional plans is observed. The mean dose to the contra-lateral breast was lowest for the RapidArc plans as well as the V(10Gy) and the maximum dose. The mean predicted ERR for the eight patients were lower for the conventional and RA plans than for the IMRT plans assuming a linear dose-risk relationship. The mean predicted ERR when using a non linear model was lower for all the three techniques (with lowest ERR for RapidArc plans)., Conclusions: From a clinical perspective, it should be concluded that all three solutions investigated in the study can offer high quality treatment of patients. Further comparative analysis of the two algorithms used in the present study, however, should be performed especially on the peripheral organ dose. The impact of CB exposure to a low-dose radiation on minimizing the risk of radiation induced malignancy in CB can be interpreted differently when using linear or non linear models to predict ERR. In general, no detriment was observed when using RapidArc compared to conventional treatments while a potentially higher risk could be associated to IMRT treatments with fixed gantry.

Purpose: To facilitate a discussion about the impact of dose heterogeneity on the risk for secondary contralateral breast (CB) cancer predicted with linear and non linear models associated with primary breast irradiation., Methods and Materials: Dose volume statistics of the CB calculated for eight patients using a collapsed cone algorithm were used to predict the excess relative risk (ERR) for cancer induction in CB. Both linear and non-linear models were employed. A sensitivity analysis demonstrating the impact of different parameter values on calculated ERR for the eight patients was also included in this study., Results: A proportionality assumption was established to make the calculations with a linear and non-linear model comparable. ERR of secondary cancer predicted by the linear model varied considerably between the patients, while the predicted ERR for the same patients using the non-linear model showed very small variation. The predicted ERRs by the two models were indistinguishable for small doses, i.e. below approximately 3 Gy. The sensitivity analysis showed that the quadratic component of the radiation-induction pre-malignant cell term is negligible for lower dose level. The ERR is highly sensitive to the value of alpha(1) and alpha(2)., Conclusions: Optimization of breast cancer radiation therapy, where also the risk for radiation induced secondary malignancies in the contralateral breast is taken into account, requires robust and valid risk assessment. The linear dose-risk model does not account for the complexity in the mechanisms underlying the development of secondary malignancies following exposure to radiation; this is particularly important when estimating risk associated with highly heterogeneous dose distributions as is the case in the contralateral breast of women receiving breast cancer irradiation.

Purpose: To measure the dose distribution in the contralateral breast (CB) following radiotherapy of the breast and regional lymph nodes by a 4-field technique, and to examine whether related treatment planning calculations of CB doses reproduce the measurements., Materials and Methods: CB doses were measured by thermoluminescence dosimetry on the surface of 8 patients and in an anthropomorphic phantom. Dose calculations at corresponding points of interest were performed by the treatment planning system Helax-TMS 6.1 using the pencil beam or the collapsed cone algorithm., Results: The measured CB doses were typically between 1% and 15% of the prescribed dose. The dose decreased significantly both in the medial-lateral and cranial-caudal direction. The average ratio of the measured to the calculated CB dose was about 0.7 and 0.9 for the pencil beam and the collapsed cone algorithm, respectively. One of the treatment fields aimed at the regional lymph nodes and some of the chest wall gave the highest contribution to the CB dose., Conclusions: The dose distribution in the CB following locoregional radiotherapy of the breast and regional lymph nodes is quite inhomogeneous. The collapsed cone algorithm may be used for estimating doses to the CB. Some concern is raised regarding the current field arrangement and the consequences for the CB dose.