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Background: Brain metastases (BM) occur in about 30% of all patients with non-small cell lung cancer (NSCLC). BM treatment guidelines recommend more frequent use of stereotactic radiotherapy (SRT). Overall, studies report no difference in overall survival (OS) comparing SRT to whole-brain radiotherapy (WBRT). We examined survival after radiotherapy for BM in a population-based sample from the South-Eastern Norway Regional Health Authority treated 2006-2018., Methods: We reviewed electronic medical records of 2140 NSCLC patients treated with SRT or WBRT for BM from 2006-2018. Overall survival (OS) was compared to predicted survival according to the prognostic systems DS-GPA and Lung-molGPA., Results: Use of SRT increased during the period, from 19% (2006-2014) to 45% (2015-2018). Median OS for all patients was 3.0 months, increasing from 2.0 (2006) to 4.0 (2018). Median OS after SRT was 7.0 months ( n  = 435) and 3.0 months after WBRT ( n  = 1705). Twenty-seven percent of SRT patients and 50% of WBRT patients died within 90 days after start of RT. Age ≥70, male sex, KPS ≤70, non-adenocarcinoma histology, ECM present, multiple BM, and WBRT were associated with shorter survival ( p  < .001). Actual mOS corresponded best with predicted mOS by DS-GPA and Lung-molGPA for the SRT group., Conclusion: Overall survival after radiotherapy (RT) for BM improved during the study period, but only for patients treated with SRT. Survival after WBRT remains poor; its use should be questioned. DS-GPA and Lung-molGPA seem most useful in predicting prognosis considered for SRT.

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 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.