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Breast cancer radiotherapy can increase the risks of heart disease, lung cancer and oesophageal cancer. At present, the best dosimetric predictors of these risks are mean doses to the whole heart, lungs and oesophagus, respectively. We aimed to estimate typical doses to these organs and resulting risks from UK breast cancer radiotherapy. A systematic review and meta-analysis was conducted of planned or delivered mean doses to the whole heart, lungs or oesophagus from UK breast cancer radiotherapy in studies published during 2015–2023. Average mean doses were summarised for combinations of laterality and clinical targets. Heart disease and lung cancer mortality risks were then estimated using established models. For whole heart, thirteen studies reported 2893 doses. Average mean doses were higher in left than in right-sided radiotherapy and increased with extent of clinical targets. For left-sided radiotherapy, average mean heart doses were: 2.0 Gy (range 1.2–8.0 Gy) breast/chest wall, 2.7 Gy (range 0.6–5.6 Gy) breast/chest wall with either axilla or supraclavicular nodes and 2.9 Gy (range 1.3–4.7 Gy) breast/chest wall with nodes including internal mammary. For right-sided radiotherapy, average mean heart doses were: 1.0 Gy (range 0.3–1.0 Gy) breast/chest wall and 1.2 Gy (range 1.0–1.4 Gy) breast/chest wall with either axilla or supraclavicular nodes. There were no whole heart dose estimates from right internal mammary radiotherapy. For whole lung, six studies reported 2230 doses. Average mean lung doses increased with extent of targets irradiated: 2.6 Gy (range 1.4–3.0 Gy) breast/chest wall, 3.0 Gy (range 0.9–5.1 Gy) breast/chest wall with either axilla or supraclavicular nodes and 7.1 Gy (range 6.7–10.0 Gy) breast/chest wall with nodes including internal mammary. For whole oesophagus, two studies reported 76 doses. Average mean oesophagus doses increased with extent of targets irradiated: 1.4 Gy (range 1.0–2.0 Gy) breast/chest wall with either axilla or supraclavicular nodes and 5.8 Gy (range 1.9–10.0 Gy) breast/chest wall with nodes including internal mammary. The typical doses to these organs may be combined with dose-response relationships to estimate radiation risks. Estimated 30-year absolute lung cancer mortality risks from modern UK breast cancer radiotherapy for patients irradiated when aged 50 years were 2–6% for long-term continuing smokers, and <1% for non-smokers. Estimated 30-year mortality risks for heart disease were <1%. • Average mean whole organ doses were ∼2 Gy for heart, 3 Gy lung, and 4 Gy oesophagus. • Organ doses increased with increasing targets irradiated. • Estimated absolute 30-year radiation heart disease mortality risks were 0.2%–0.7%. • Equivalent lung cancer risks were 0.2%–0.4% for non-smokers and 2.3%–6.2% for smokers. [ABSTRACT FROM AUTHOR]

Purpose: The use of volumetric modulated arc therapy (VMAT), simultaneous integrated boost (SIB), and hypofractionated regimen requires adequate patient setup accuracy to achieve an optimal outcome. The purpose of this study was to assess the setup accuracy of patients receiving left‐sided breast cancer radiotherapy using deep inspiration breath‐hold technique (DIBH) and surface guided radiotherapy (SGRT) and to calculate the corresponding setup margins. Methods: The patient setup accuracy between and within radiotherapy fractions was measured by comparing the 6DOF shifts made by the SGRT system AlignRT with the shifts made by kV‐CBCT. Three hundred and three radiotherapy fractions of 23 left‐sided breast cancer patients using DIBH and SGRT were used for the analysis. All patients received pre‐treatment DIBH training and visual feedback during DIBH. An analysis of variance (ANOVA) was used to test patient setup differences for statistical significance. The corresponding setup margins were calculated using the van Herk's formula. Results: The intrafractional patient setup accuracy was significantly better than the interfractional setup accuracy (p < 0.001). The setup margin for the combined inter‐ and intrafractional setup error was 4, 6, and 4 mm in the lateral, longitudinal, and vertical directions if based on SGRT alone. The intrafractional error contributed ≤1 mm to the calculated setup margins. Conclusion: With SGRT, excellent intrafractional and acceptable interfractional patient setup accuracy can be achieved for the radiotherapy of left‐sided breast cancer using DIBH and modern radiation techniques. This allows for reducing the frequency of kV‐CBCTs, thereby saving treatment time and radiation exposure. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate three techniques of irradiation of left-sided breast cancer patients, three-dimensional conformal radiotherapy (3D-CRT), hybrid Intensity-Modulated Radiotherapy (h-IMRT), and hybrid Volumetric-Modulated Arc Therapy (h-VMAT, h-ARC), in terms of dose distribution in the planning target volume (PTV) and organs at risk (OARs). The second aim was to estimate the projected relative risk of radiation-induced secondary cancers for hybrid techniques. Three treatment plans were prepared in 3D-CRT, h-IMRT, and h-VMAT techniques for each of the 40 patients, who underwent CT simulation in deep inspiration breath-hold (DIBH). For hybrid techniques, plans were created by combining 3D-CRT and dynamic fields with an 80%/20% dose ratio for 3D-CRT and IMRT or VMAT. Cumulative dose–volume histograms were used to compare dose distributions within the PTV and OARs (heart, left anterior descending coronary artery [LAD], left and right lung [LL, RL], right breast [RB]). Projected risk ratios for secondary cancers were estimated relative to 3D-CRT using the organ equivalent dose (OED) concept for the Schneider's linear exponential, plateau, and full mechanistic dose–response model. All plans fulfilled the PTV criterium: V95%≥95%. Compared to 3D-CRT, both hybrid techniques showed significantly better target coverage (PTV: V95%>98%, p < 0.001), and the best conformality was achieved by h-ARC plans (CI: 1.18 ± 0.09, p < 0.001). Compared to 3D-CRT and h-ARC, h-IMRT increased the average sum of monitor units (MU) over 129.9% (p < 0.001). H-ARC increased the mean dose of contralateral organs and the LL V5Gy parameter (p < 0.001). Both hybrid techniques significantly reduced the Dmax of the heart by 5 Gy. Compared to h-IMRT, h-ARC increased secondary cancer projected relative risk ratios for LL, RL, and RB by 18, 152, and 81%, respectively. The results confirmed that both hybrid techniques provide better target quality and OARs sparing than 3D-CRT. Hybrid VMAT delivers less MU compared to hybrid IMRT but may increase the risk of radiation-induced secondary malignancies. [ABSTRACT FROM AUTHOR]

Background: Previous studies in 2D and in 3D conformal radiotherapy concludes that the maximal heart distance and the mean heart dose (MHD) are considered predictive of late cardiac toxicities. As the use of inverse-planned intensity modulated radiation therapy (IMRT) is increasing worldwide, we hypothesized that this 3D MHD might not be representative of heart exposure after IMRT for breast cancer (BC). Methods: Patients with left-sided BC and unfavorable cardiac anatomy received IMRT. Their treatment plan was compared to a virtual treatment plan for 3D conformal radiotherapy with similar target volume coverage (study A). Then, a second 3D conformal treatment plan was generated to achieve equivalent individual MHD obtained by IMRT. Then the heart and left anterior descending (LAD) coronary artery exposures were analyzed (study B). Last, the relationship between MHD and the heart volume or LAD coronary artery volume receiving at least 30Gy, 40Gy and 45Gy in function of each additional 1Gy to the MHD was assessed (study C). Results: A significant decrease of heart and LAD coronary artery exposure to high dose was observed with the IMRT compared with the 3D conformal radiotherapy plans that both ensured adequate target coverage (study A). The results of study B and C showed that 3D MHD was not representative of similar heart substructure exposure with IMRT, especially in the case of high dose exposure. Conclusions: The mean heart dose is not a representative dosimetric parameter to assess heart exposure following IMRT. Equivalent MHD values following IMRT and 3DRT BC treatment do not represent the same dose distribution leading to extreme caution when using this parameter for IMRT plan validation. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to compare two techniques of irradiation of left-sided breast cancer patients who underwent breast-conserving surgery, three-dimensional conformal radiotherapy technique (3D-CRT) and volumetric modulated arc therapy (VMAT), in terms of dose distribution in the planning target volume (PTV) and organs at risk (OARs). The second aim of the study was estimation of the projected risk of radiation-induced secondary cancer for both radiotherapy techniques. Materials and methods: For 25 patients who underwent CT simulation in deep inspiration breath-hold (DIBH), three treatment plans were generated: one using a three-dimensional conformal radiotherapy technique and two using volumetric modulated arc therapy. First VMAT-DIBH geometry consisted of three partial arcs (ARC-DIBH 3A) and second consisted of four partial arcs (ARC-DIBH 4A). Cumulative dose–volume histograms (DVHs) were used to compare dose distributions within the PTV and OARs (heart, left anterior descending coronary artery [LAD], ipsilateral and contralateral lung [IL, CL], and contralateral breast [CB]). Normal tissue complication probabilities (NTCPs) and organ equivalent doses (OEDs) were calculated using the differential DVHs. Excess absolute risks (EARs) for second cancers were estimated using Schneider's full mechanistic dose–response model. Results: All plans fulfilled the criterium for PTV V95% ≥ 95%. The PTV coverage, homogeneity, and conformity indices were significantly better for VMAT-DIBH. VMAT showed a significantly increased mean dose and V5Gy for all OARs, but reduced LAD Dmax by 15 Gy. For IL, CL, and CB, the 3D-CRT DIBH method achieved the lowest values of EAR: 28.38 per 10,000 PYs, 2.55 per 10,000 PYs, and 4.48 per 10,000 PYs (p < 0.001), compared to 40.29 per 10,000 PYs, 15.62 per 10,000 PYs, and 23.44 per 10,000 PYs for ARC-DIBH 3A plans and 41.12 per 10,000 PYs, 15.59 per 10,000 PYs, and 22.73 per 10,000 PYs for ARC-DIBH 4A plans. Both techniques provided negligibly low NTCPs for all OARs. Conclusion: The study shows that VMAT-DIBH provides better OAR sparing against high doses. However, the large low-dose-bath (≤ 5 Gy) is still a concern due to the fact that a larger volume of normal tissues exposed to lower doses may increase a radiation-induced risk of secondary cancer. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate normal lung and heart tissue doses for treatment of left-sided breast cancer in deep inspiration breath-hold (DIBH) and free breathing (FB) as a function of breast size and diaphragm displacement using 4D-XCAT digital phantom in a simulation study. Materials and Methods: 4D-XCAT digital phantom was used to create 36 left-sided breast cancer digital phantom datasets with different breast height (BH) of 40, 50, and 60 mm, breast length (BL) of 16, 17, and 18 mm, and diaphragm excursion of 20, 25, 30, and 35 mm. For each dataset, DIBH and FB treatment plans were prepared using planning computerized radiotherapy-three dimensional (PCRT-3D) treatment planning system (TPS) with superposition computational algorithm. Dose differences in DIBH and FB plans were assessed in terms of mean lung dose (MLD), the lung volume receiving ≤20 Gy (V20), normal tissue complication probability (NTCP) of the lung, mean heart dose (MHD), and the heart volume receiving ≤30 (V30). Results: DIBH reduced mean dose and V20 and NTCP of the lung in all cases, by up to 4.37 Gy, 7.62%, and 18.95%. Mean dose and V30 of the heart were also significantly reduced by 5.02 Gy and 8.23%. Conclusions: The use of DIBH for left-sided breast cancer radiotherapy offers excellent possibilities for sparing critical normal tissue without compromising radiation dose to the target. [ABSTRACT FROM AUTHOR]

Objective: Treatment side effects lead to a negative impact on the quality of life in breast cancer survivors. Exercise is reported to improve the physical and psychological status of these patients. We aimed to investigate the effect of exercise during radiotherapy on physical and psychological status in breast cancer patients. Material and Method: A randomized controlled study was set in outpatient rehabilitation clinic. Histologically proven stage I-III breast cancer patients referred for adjuvant radiotherapy were randomly assigned to a supervised aerobic and strengthening exercise program or usual medical care without exercise training. The primary outcome parameters were Rosenberg Self Esteem Scale (RSES), Short Form-36 (SF_36) Quality of life, Coping Strategies Questionnaire (COPE Inventory), Fatigue Severity Scale (FSS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI). End points were assessed 1 week prior to and 1 week following 6 weeks of exercise training. Results: In the repeated measured analysis, BAI and FSS scores decreased, general health (GH) and energy/fatigue (E) scores of SF-36 increased in the exercise group (p=0.045, Cohen d=0.757 for BAI, p=0.02, Cohen d=0.863, p=0.010, Cohen d =1.02 for GH, p=0.032, Cohen d=0.801 for E), while the use of problem-based coping score decreased in the control group (p=0.049, Cohen d=0.641). No significant differences were found in scores for BDI and RSES (p>0.05). Conclusion: In conclusion, supervised comined exercise training during adjuvant radiotherapy improved anxiety, fatigue, energy, general health perceptions and prevented decreasing in using effective coping strategies. [ABSTRACT FROM AUTHOR]

Background and purpose: In accelerated partial breast irradiation (APBI), accurate definition of the tumour bed is crucial to reduce the risk of local recurrence and the volume of healthy tissue irradiated. Recently, hydrogels have been proposed to improve visibility of the lumpectomy cavity for APBI. The aim of this study was to alter two commercially available hyaluronic acid (HA) gels, with gadopentenate dimeglumine (GD), a magnetic resonance imaging (MRI) contrast agent. We hypothesize that after injection in the surgical cavity, the mixtures will be visible with computed tomography (CT) for improved treatment planning, cone-beam CT (CBCT) for improved patient setup and planar kilovoltage (kV) x-ray for real-time tracking during treatment. Materials and methods: In this ex vivo study, GD was mixed with the two HA gels, and 1 mL of each mixture was injected into fatty and muscular tissue of a pork phantom. Visibility with CT, CBCT and planar x-ray imaging was assessed. Contrast-to-noise ratios (CNR) were measured and compared to commercially available iodinated polyethylene glycol (PEG). Results: The gel mixtures showed increased visibility over HA gels without GD. When comparing CNR of the gel mixtures to that of iodinated PEG on CT, there was a 4-fold increase in muscle for both mixtures and a 1.6-fold to 3.6-fold increase in fat, depending on the HA gel. Gel mixtures showed better visibility with planar kV imaging over iodinated PEG. Conclusion: Addition of GD to HA gels increases visibility with CT, CBCT and planar x-ray imaging, indicating potential for improved delineation and positioning in APBI.

BackgroundPrevious studies in 2D and in 3D conformal radiotherapy concludes that the maximal heart distance and the mean heart dose (MHD) are considered predictive of late cardiac toxicities. As the use of inverse-planned intensity modulated radiation therapy (IMRT) is increasing worldwide, we hypothesized that this 3D MHD might not be representative of heart exposure after IMRT for breast cancer (BC).MethodsPatients with left-sided BC and unfavorable cardiac anatomy received IMRT. Their treatment plan was compared to a virtual treatment plan for 3D conformal radiotherapy with similar target volume coverage (study A). Then, a second 3D conformal treatment plan was generated to achieve equivalent individual MHD obtained by IMRT. Then the heart and left anterior descending (LAD) coronary artery exposures were analyzed (study B). Last, the relationship between MHD and the heart volume or LAD coronary artery volume receiving at least 30Gy, 40Gy and 45Gy in function of each additional 1Gy to the MHD was assessed (study C).ResultsA significant decrease of heart and LAD coronary artery exposure to high dose was observed with the IMRT compared with the 3D conformal radiotherapy plans that both ensured adequate target coverage (study A). The results of study B and C showed that 3D MHD was not representative of similar heart substructure exposure with IMRT, especially in the case of high dose exposure.ConclusionsThe mean heart dose is not a representative dosimetric parameter to assess heart exposure following IMRT. Equivalent MHD values following IMRT and 3DRT BC treatment do not represent the same dose distribution leading to extreme caution when using this parameter for IMRT plan validation.

The aim of TROG 14.04 was to assess the feasibility of deep inspiration breath hold (DIBH) and its impact on radiation dose to the heart in patients with left-sided breast cancer undergoing radiotherapy. Secondary end points pertained to patient anxiety and cost of delivering a DIBH programme. The study comprised two groups – left-sided breast cancer patients engaging DIBH and right-sided breast cancer patients using free breathing through radiotherapy. The primary end point was the feasibility of DIBH, defined as left-sided breast cancer patients' ability to breath hold for 15 s, decrease in heart dose in DIBH compared with the free breathing treatment plan and reproducibility of radiotherapy delivery using mid-lung distance (MLD) assessed on electronic portal imaging as the surrogate. The time required for treatment delivery, patient-reported outcomes and resource requirement were compared between the groups. Between February and November 2018, 32 left-sided and 30 right-sided breast cancer patients from six radiotherapy centres were enrolled. Two left-sided breast cancer patients did not undergo DIBH (one treated in free breathing as per investigator choice, one withdrawn). The mean heart dose was reduced from 2.8 Gy (free breathing) to 1.5 Gy (DIBH). Set-up reproducibility in the first week of treatment assessed by MLD was 1.88 ± 1.04 mm (average ± 1 standard deviation) for DIBH and 1.59 ± 0.93 mm for free breathing patients. Using a reproducibility cut-off for MLD of 2 mm (1 standard deviation) as per study protocol, DIBH was feasible for 67% of DIBH patients. Radiotherapy delivery using DIBH took about 2 min longer than for free breathing. Anxiety was not significantly different in DIBH patients and decreased over the course of treatment in both groups. Although DIBH was shown to require about 2 min longer per treatment slot, it has the potential to reduce heart dose in left-sided breast cancer patients by nearly a half, provided careful assessment of breath hold reproducibility is carried out. • Deep inspiration breath hold (DIBH) was assessed in a prospective, multicentre trial as a means of reproducibly reducing dose to the heart. • DIBH was confirmed in plans of 30 patients from six institutions to reduce dose to the heart by about 45% compared with free breathing. • DIBH added about 2 min to the treatment time compared with right-sided breast patients treated in the same institutions using free breathing. • There was no difference in anxiety assessed on a visual analogue scale between DIBH patients compared with free breathing patients. [ABSTRACT FROM AUTHOR]

Zhikai Liu,1 Fangjie Liu,2,&ast; Wanqi Chen,1,&ast; Yinjie Tao,1 Xia Liu,1 Fuquan Zhang,1 Jing Shen,1 Hui Guan,1 Hongnan Zhen,1 Shaobin Wang,3 Qi Chen,3 Yu Chen,3 Xiaorong Hou1 1Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 2Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China; 3MedMind Technology Co., Ltd., Beijing, 100055, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaorong Hou Tel +86 138 1196 3013Email hxr_pumch@163.comObjective: Delineation of clinical target volume (CTV) and organs at risk (OARs) is important for radiotherapy but is time-consuming. We trained and evaluated a U-ResNet model to provide fast and consistent auto-segmentation.Methods: We collected 160 patients’ CT scans with breast cancer who underwent breast-conserving surgery (BCS) and were treated with radiotherapy. CTV and OARs were delineated manually and were used for model training. The dice similarity coefficient (DSC) and 95th percentile Hausdorff distance (95HD) were used to assess the performance of our model. CTV and OARs were randomly selected as ground truth (GT) masks, and artificial intelligence (AI) masks were generated by the proposed model. Two clinicians randomly compared CTV score differences of the contour. The consistency between two clinicians was tested. Time cost for auto-delineation was evaluated.Results: The mean DSC values of the proposed method were 0.94, 0.95, 0.94, 0.96, 0.96 and 0.93 for breast CTV, contralateral breast, heart, right lung, left lung and spinal cord, respectively. The mean 95HD values were 4.31mm, 3.59mm, 4.86mm, 3.18mm, 2.79mm and 4.37mm for the above structures, respectively. The average CTV scores for AI and GT were 2.89 versus 2.92 when evaluated by oncologist A (P=0.612), and 2.75 versus 2.83 by oncologist B (P=0.213), with no statistically significant differences. The consistency between two clinicians was poor (kappa=0.282). The time for auto-segmentation of CTV and OARs was 10.03 s.Conclusion: Our proposed model (U-ResNet) can improve the efficiency and accuracy of delineation compared with U-Net, performing equally well with the segmentation generated by oncologists.Keywords: clinical target volume, organ at risk, auto-segmentation, breast cancer radiotherapy, clinical evaluation

Summary: Background: The role of post-mastectomy radiotherapy (PMRT) for breast cancer is controversial when 3-or-less lymph nodes are metastatic. Apart from local control, survival and toxicity, cost also plays an important role in decision-making. Methods: A Markov model was designed to assess cost, health outcomes and cost-effectiveness of different radiotherapy techniques for management of PMRT patients. Thirty-nine scenarios were modelled based on type of radiotherapy, laterality, pathologic nodal burden, and dose fractionation. We considered a societal perspective, lifetime horizon and a 3% discount rate. The data on quality of life (QoL) was derived using the cancer database on cost and QoL. Published data on cost of services delivered in India were used. Findings: Post-mastectomy radiotherapy results in incremental quality adjusted life years (QALYs) that ranged from −0.1 to 0.38 across different scenarios. The change in cost ranged from estimated median savings of USD 62 (95% confidence intervals: −168 to −47) to incurring an incremental cost of USD 728 (650–811) across different levels of nodal burden, breast laterality and dose fractionation. For women with node-negative disease, disease-specific systemic therapy remains to be the preferred strategy. For women with node-positive disease, two-dimensional radiotherapy (2DRT) with hypofractionation is the most cost-effective strategy. However, a CT based planning is preferred when maximum heart distance (MHD) >1cm, irregular chest wall contour and inter-field separation >18cm. Interpretation: PMRT is cost-effective for all node-positive patients. With similar toxicity and effectiveness profile compared with conventional fractionation, moderate hypofractionation significantly reduces the cost of treatment and should be the standard of care. Conventional techniques for PMRT are cost-effective over newer modalities which provide minimal additional benefit, at high cost. Funding: The funding to collect primary data for study was provided by Department of Health Research, Ministry of Health and Family Welfare, New Delhi, wide letter number F. No. T.11011/02/2017-HR/3100291.

Purpose: It is known that the diagnosis of breast cancer often causes anxiety and depression. Radiotherapy of the breast as an obligatory part of a breast-conserving treatment concept can markedly increase these psychological symptoms in many, but not all patients. In this clinical observational study, we aimed at identifying cognitive, health-related and social factors that may either enhance or reduce the emergence of anxiety and depression. Methods: Using a longitudinal study design with 25 women (mean age: 52.9 years; SD = 10.6; age range 29–70 years) with a first diagnosis of nonmetastatic breast cancer, measures of anxiety, depression, situational emotional states, intelligence, and aspects of social frameworks were assessed before, during, and after radiotherapy of the breast. At 4 time-points, standard and self-constructed questionnaires were used to assess the course of anxiety and depressive symptoms across the radiotherapy intervention. Results: We found that anxiety is highest immediately before the start of radiation therapy, while the anxiety level was lowest on the day that therapy was completed. Anxiety and depression were enhanced in women with a lifetime history of chronic diseases at all time points of measurement. Moreover, women with high intelligence and low social support had stronger symptoms of depression than women with low intelligence and a stable family background at some time points of measurement. The degree of anxiety was neither related to intelligence nor to social support. Conclusion: For the first time, we demonstrate empirical pilot data on cognitive and social modulators of anxiety and depression in women with breast cancer over the course of radiotherapy. Our results may help to optimize clinical procedures and thereby reduce symptoms of anxiety and depression in these patients. [ABSTRACT FROM AUTHOR]

Melittin, a major peptide constituent of bee venom, exhibits potential anticancer effects against various types of cancers, including breast cancer. We determined the radiosensitizing effects of melittin on breast cancer both in vitro and in vivo models. Viability of murine (4T1) and human (MCF-7) breast cancer cell lines treated with melittin was measured by MTT assay. The radiosensitizing effects of melittin were investigated using a clonogenic assay. The expression of apoptosis-related proteins was assessed by Western blotting. Tumor growth with/without melittin treatment was investigated in a 4T1 xenograft breast cancer mouse model. Melittin-mediated radiosensitivity was evaluated by assessing growth inhibitory activity based on the change in tumor volume and the time taken for a five-fold increase in the relative tumor volume (RTV5). Melittin inhibited the viability of 4T1 and MCF-7 breast cancer cells with IC50 of 1.70 and 1.51 μM, respectively. Melittin decreased clonogenicity with a sensitization enhancement ratio of 1.09–1.32. Melittin plus irradiation significantly increased the Bax/Bcl-2 ratio. In vivo, intraperitoneal injection of melittin significantly reduced tumor growth in 4T1 tumor-bearing mice. Melittin plus irradiation treatment increased the tumor growth inhibition rate (87.97%) as compared with the control group and had the greatest effect on tumor growth inhibition with the longest RTV5 of 37.0 days. Irradiation alone, melittin alone, and control treatment showed RTV5 of 24.4, 16.2, and 13.6 days, respectively. By inducing apoptosis, melittin serves as a promising radiosensitizer for breast cancer radiotherapy, providing a valuable strategy to improve the efficacy of radiation therapy. [ABSTRACT FROM AUTHOR]

• Addresses low-density lung description in MC reference dose calculations. • Experimental measurements in air-filled phantom, corresponding MC calculations. • Mass density characterization had large effect on the lung dose distribution. • The effect of air/lung differentiation was not dominating. • Dosimetry effects quantified for 15 clinical plans. To investigate the sensitivity of Monte Carlo (MC) calculated lung dose distributions to lung tissue characterization in external beam radiotherapy of breast cancer under Deep Inspiration Breath Hold (DIBH). EGSnrc based MC software was employed. Mean lung densities for one hundred patients were analysed. CT number frequency and clinical dose distributions were calculated for 15 patients with mean lung density below 0.14 g/cm3. Lung volume with a pre-defined CT numbers was also considered. Lung tissue was characterized by applying different CT calibrations in the low-density region and air-lung tissue thresholds. Dose impact was estimated by Dose Volume Histogram (DVH) parameters. Mean lung densities below 0.14 g/cm3 were found in 10% of the patients. CT numbers below −960 HU dominated the CT frequency distributions with a high rate of CT numbers at −990 HU. Mass density conversion approach influenced the DVH shape. V 4Gy and V 8Gy varied by 7% and 5% for the selected patients and by 9% and 3.5% for the pre-defined lung volume. V 16Gy and V 20Gy , were within 2.5%. Regions above 20 Gy were affected. Variations in air- lung tissue differentiation resulted in DVH parameters within 1%. Threshold at −990 HU was confirmed by the CT number frequency distributions. Lung dose distributions were more sensitive to variations in the CT calibration curve below lung (inhale) density than to air-lung tissue differentiation. Low dose regions were mostly affected. The dosimetry effects were found to be potentially important to 10% of the patients treated under DIBH. [ABSTRACT FROM AUTHOR]

Currently available prone support devices for breast cancer radiotherapy show different limitations, such as inconsistent patient positioning, patient discomfort and limited beam accessibility. Furthermore, medical devices tend to be developed with a top-down waterfall approach. For devices with complex use scenarios, this may impact efficacy. Therefore, we developed a patient support device with a Research through Design approach, supported by a co-design trajectory with different stakeholders. In this deductive case study, we analyze our development approach. We reflect on the NIH's T-phases of translational research and the Stanford BioDesign Process. We conclude that the user-centred and iterative aspects of our approach were beneficial to the regulatory process and the quality of the product. Furthermore, cooperating with a university hospital enhanced the regulatory process by its access to clinical data. The outcomes of this interdisciplinary research may be beneficial to other types of cancer such as lung cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To elucidate whether (1) a posterior axillary boost (PAB) field is an optimal method to target axillary lymph nodes (LNs); and (2) the addition of a PAB increases the incidence of lymphedema, a systematic review was undertaken. A literature search was performed in the PubMed database. A total of 16 studies were evaluated. There were no randomized studies. Seven articles have investigated dosimetric aspects of a PAB. The remaining 9 articles have determined the effect of a PAB field on the risk of lymphedema. Only 2 of 9 articles have prospectively reported the impact of a PAB on the risk of lymphedema development. There are conflicting reports on the necessity of a PAB. The PAB field provides a good coverage of level I/II axillary LNs because these nodes are usually at a greater depth. The main concern regarding a PAB is that it produces a hot spot in the anterior region of the axilla. Planning studies optimized a traditional PAB field. Prospective studies and the vast majority of retrospective studies have reported the use of a PAB field does not result in increasing the risk of lymphedema development over supraclavicular-only field. The controversies in the incidence of lymphedema suggest that field design may be more important than field arrangement. A key factor regarding the use of a PAB is the depth of axillary LNs. The PAB field should not be used unless there is an absolute indication for its application. Clinicians should weigh lymphedema risk in individual patients against the limited benefit of a PAB, in particular after axillary dissection. The testing of the inclusion of upper arm lymphatics in the regional LN irradiation target volume, and universal methodology measuring lymphedema are all areas for possible future studies. [ABSTRACT FROM AUTHOR]

With improved survival outcomes of patients with cancer, cardiovascular diseases have become an important part of morbidity and mortality. In recent years, there has been much interest in the literature on the impact of radiotherapy on the late cardiac toxicity. Various cardiac dose-volume constraints have been reported in association with cardiovascular events and mortality, but without consistent constraint. Low-dose heart exposure in adjuvant breast cancer radiotherapy can lead to important cardiac events in decade or more after treatment. However, in radical lung cancer radiotherapy, high-dose heart exposure can lead to increased cardiovascular mortality in the first years after treatment. We can further influence the survival of patients with cancer after chest irradiation by lowering the absorbed dose to the heart, which is already made possible by better irradiation techniques and image-guided radiotherapy. Additional benefits can be gained by better understanding and considering the impact of radiation on individual cardiac structures, also in connection with other patients’ comorbidities, and by close cardiac follow-up of patients after chest radiation therapy.

Proton therapy has been proposed as a technique to improve the long-term quality of life of breast cancer patients. This is due to its ability to reduce the dose to healthy tissue compared to conventional X-ray therapy. The aim of this study was to investigate the risk of secondary carcinogenesis due to proton therapy compared to hybrid IMRT for breast treatments. In this study, the Pinnacle treatment planning system was used to simulate treatment plans for 15 female left-sided whole breast cancer patients with deep inspiration breath hold scans. Two treatment plans were generated for each patient: hybrid intensity modulated radiotherapy (h-IMRT) and intensity modulated proton therapy (IMPT). Using the dose-volume histograms (DVHs) from these plans, the mean lifetime attributed risk (LAR) for both lungs and the contralateral breast were evaluated using the BEIR VII and Schneider full risk models. The results from both risk models show lower LAR estimates for the IMPT treatment plan compared to the h-IMRT treatment plan. This result was observed for all organs of interest and was consistent amongst the two separate risk models. For both treatment plans, the organs from most to least at risk were: ipsilateral lung, contralateral breast, and contralateral lung. In all cases, the risk estimated via the BEIR VII model was higher that the Schneider full risk model. The use of proton therapy for breast treatments leads to reduced risk estimates for secondary carcinogenesis. Therefore, proton therapy shows promise in improving the long term treatment outcome of breast patients. [ABSTRACT FROM AUTHOR]

BackgroundThis study aims to construct and validate a model based on convolutional neural networks (CNNs), which can fulfil the automatic segmentation of clinical target volumes (CTVs) of breast cancer for radiotherapy.MethodsIn this work, computed tomography (CT) scans of 110 patients who underwent modified radical mastectomies were collected. The CTV contours were confirmed by two experienced oncologists. A novel CNN was constructed to automatically delineate the CTV. Quantitative evaluation metrics were calculated, and a clinical evaluation was conducted to evaluate the performance of our model.ResultsThe mean Dice similarity coefficient (DSC) of the proposed model was 0.90, and the 95th percentile Hausdorff distance (95HD) was 5.65 mm. The evaluation results of the two clinicians showed that 99.3% of the chest wall CTV slices could be accepted by clinician A, and this number was 98.9% for clinician B. In addition, 9/10 of patients had all slices accepted by clinician A, while 7/10 could be accepted by clinician B. The score differences between the AI (artificial intelligence) group and the GT (ground truth) group showed no statistically significant difference for either clinician. However, the score differences in the AI group were significantly different between the two clinicians. The Kappa consistency index was 0.259. It took 3.45 s to delineate the chest wall CTV using the model.ConclusionOur model could automatically generate the CTVs for breast cancer. AI-generated structures of the proposed model showed a trend that was comparable, or was even better, than those of human-generated structures. Additional multicentre evaluations should be performed for adequate validation before the model can be completely applied in clinical practice.

Background: This study aims to construct and validate a model based on convolutional neural networks (CNNs), which can fulfil the automatic segmentation of clinical target volumes (CTVs) of breast cancer for radiotherapy. Methods: In this work, computed tomography (CT) scans of 110 patients who underwent modified radical mastectomies were collected. The CTV contours were confirmed by two experienced oncologists. A novel CNN was constructed to automatically delineate the CTV. Quantitative evaluation metrics were calculated, and a clinical evaluation was conducted to evaluate the performance of our model. Results: The mean Dice similarity coefficient (DSC) of the proposed model was 0.90, and the 95th percentile Hausdorff distance (95HD) was 5.65 mm. The evaluation results of the two clinicians showed that 99.3% of the chest wall CTV slices could be accepted by clinician A, and this number was 98.9% for clinician B. In addition, 9/10 of patients had all slices accepted by clinician A, while 7/10 could be accepted by clinician B. The score differences between the AI (artificial intelligence) group and the GT (ground truth) group showed no statistically significant difference for either clinician. However, the score differences in the AI group were significantly different between the two clinicians. The Kappa consistency index was 0.259. It took 3.45 s to delineate the chest wall CTV using the model. Conclusion: Our model could automatically generate the CTVs for breast cancer. AI-generated structures of the proposed model showed a trend that was comparable, or was even better, than those of human-generated structures. Additional multicentre evaluations should be performed for adequate validation before the model can be completely applied in clinical practice. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer in women worldwide and encompasses a broad spectrum of diseases in one with significant epidemiological, clinical, and biological heterogeneity, which determines a different natural history and prognostic profile. Although classical tumour staging (TNM) still provides valuable information, the current reality is that the clinicians must consider other biological and molecular factors that directly influence treatment decision-making. The management of breast cancer has changed radically in the last 15 years due to significant advances in our understanding of these tumours. This knowledge has brought with it a major impact regarding surgical and systemic management and has been practice-changing, but it has also created significant uncertainties regarding how best integrate the radiotherapy treatment into the therapeutic scheme. In parallel, radiotherapy itself has also experienced major advances, new radiobiological concepts have emerged, and genomic data and other patient-specific factors must now be integrated into individualised treatment approaches. In this context, "precision medicine" seeks to provide an answer to these open questions and uncertainties. The aim of the present review is to clarify the meaning of this term and to critically evaluate its role and impact on contemporary breast cancer radiotherapy. [ABSTRACT FROM AUTHOR]

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• Manual contouring consistency increased relative to modern guidelines during trial. • Cardiac doses decreased over the study duration. • Mean whole heart dose is highly correlated with mean doses to cardiac substructures. • Predictive models: a useful tool for retrospective datasets. Radiotherapy for breast cancer can increase the risks of heart disease. Patient-specific risk assessment may be improved with the inclusion of doses to cardiac substructures. The purpose of this work was to use automatic segmentation to evaluate substructure doses and develop predictive models for these based on the dose to the whole heart. Automatic segmentation was used to delineate cardiac substructures in a Danish breast cancer trial (DBCG HYPO) dataset comprising over 1500 Danish women treated between 2009 and 2014. Trends in contouring practices and cardiac doses over time were investigated, and models to predict substructure doses from whole heart dose parameters were fit to the data. Manual contouring consistency improved over the study period when compared with automatic segmentation; systematic differences between automatically and manually defined heart volume decreased from 106 cm3 to 12.0 cm3. Doses to the heart and cardiac substructures also decreased. Mean whole heart doses for left-sided treatments in 2009 and 2014 were 1.94 ± 1.19 Gy and 1.29 ± 0.69 Gy (average ± SD), respectively. Prediction of mean substructure doses is accurate, with R2 scores in the range 0.45–0.95 (average 0.77), depending on the particular structure. This study reports heart and cardiac substructure doses in a large breast cancer cohort. Predictive models generated in this work can be used to estimate mean cardiac substructure doses for datasets where patient imaging and dose distributions are not available, provided the tangential field techniques are consistent with those used in the trial. [ABSTRACT FROM AUTHOR]

Background: Up to 95% of irradiated patients suffer from ionizing radiation (IR) induced early skin reaction, acute radiation dermatitis (ARD). Some experts think that additional skin hydration can reduce acute skin reactions. Individual radiosensitivity (IRS) determined from lymphocytes may help to predict acute radiation toxicity. The purpose of this study is to evaluate the clinical manifestation of ARD in different skincare groups during whole breast radiotherapy depending on IRS and other risk factors. Methods: A total of 108 early-stage breast cancer patients were randomized into best supportive care (BSC) and additional skincare (ASC) groups. IRS was evaluated using a G2 assay modified with caffeine-induced G2 checkpoint arrest. All patients received a 50 Gy dose to the breast planning target volume (PTV). Clinical assessment of ARD symptoms according to the CTCAE grading scale was performed once a week. Results: IRS was successfully determined for 91 out of 108 patients. A total of 10 patients (11%) had normal IRS, 47 patients (52%) were categorized as radiosensitive, and 34 (37%) as highly radiosensitive. There was no significant difference in the manifestation of ARD between patient groups by skincare or IRS. According to logistic regression, patients with bigger breasts were prone to more severe ARD (p = 0.002). Conclusions: The additional skincare did not improve skin condition during RT. A total of 89% of patients had increased radiosensitivity. IRS determined before RT did not show the predictive value for the manifestation of ARD. Logistic regression revealed that breast volume was the most significant risk factor for the manifestation of ARD.

• Automated heart edge detection in cine MV images was proposed and developed. • Highly efficient detection of heart irradiation in breast cancer radiotherapy. • Allows unmonitored surveillance of heart irradiation during breast treatments. To develop robust automated detection of heart irradiation in continuous portal images (cine MV images) of tangential breast cancer treatments. Cine MV images of 302 tangential field deliveries were recorded for ten left-sided breast cancer patients receiving deep-inspiration breath-hold radiotherapy. An algorithm for fully automated heart edge detection in cine MV images was developed and tested for all images. The algorithm first enhances the heart edge contrast greatly by exploiting that pixels on the heart edge change their intensity cyclically, and highly correlated, at 1–3 Hz due to heartbeat. The algorithm then detects the heart edge in the enhanced image and calculates the exposed heart area within the field aperture. The algorithm correctly identified the heart edge in all cine MV series with heart exposure (169 of 302 field deliveries). With conservative selection criteria the algorithm on average identified 70 heart edge pixels in the heart-including field deliveries (range: 10–230) without false positives. With less strict criteria 106 heart edge pixels were identified on average (range: 13–262) with 0.6% being false positives. The heart edge bordering the lung was segmented highly reliably even a few millimeters outside the field edge. For six patients with frequent heart irradiation, the exposed heart area showed large interfraction variations and smaller intrafraction variations. Automated heart edge detection in cine MV images was proposed, developed and shown to be highly efficient for heart exposure detection in tangential breast fields. It may allow unsupervised surveillance of heart exposure at all tangential breast cancer treatments in a clinic. [ABSTRACT FROM AUTHOR]

The goal of this study was to determine whether a delay in starting treatment via surgery or neoadjuvant chemotherapy is related to a decrease in cancer-specific survival (CSS) in women with operable breast cancer (BrCr). Limited medical infrastructure and a lack of cancer prevention awareness in low- and middle-income countries have caused high BrCr incidence and mortality rates. We analyzed a retrospective cohort of 720 women treated at a single center from 2005 to 2012. CSS estimates were obtained by the Kaplan-Meier method. A Cox model of proportional risks was performed to obtain the risk of dying from BrCr. We also obtained the risk according to the category of treatment initiation. Women with locally advanced stages and without hormone receptor expression were more likely to initiate treatment after 45 days. Patients in Stage IIIA had a 78.1% survival if treatment was initiated before 45 days (95% CI, 0.70–0.84) and 63.6% survival if treatment was started after 45 days (95% CI, 0.44–0.78; p < 0.001). Patients in Stage IIIB had a 62.9% survival if treatment was initiated before 45 days (95% CI, 0.53–0.72) and 57.4% survival if treatment started after 45 days (95% CI, 0.31-0.89; p < 0.001). Prognostic factors in which lower survival was recognized were Stage IIIA, Stage IIIB, treatment initiation after 45 days, and triple-negative tumors. The initiation of treatment within the first 45 days of diagnosis of BrCr in women portends better survival compared with those who began treatment longer than 45 days from diagnosis. [ABSTRACT FROM AUTHOR]

Background and purpose: Breast‑conserving surgery followed by radiation therapy to the whole breast is now recognized as a standard strategy in patients with breast cancer. Recommended technique for radiotherapy is whole breast irradiation followed by boost to the tumor bed. This study aimed to compare the dosimetric parameters of electron and photon beams for boosting irradiation in post‑lumpectomy patients of breast cancer. Materials and methods: This analytical study included 50 patients of post-lumpectomy breast cancer. Treatment Planning System (TPS) was used to compare the plans for electron beam and photon beam boost irradiation. The organs at risk (OAR) consist of heart, ipsilateral lung, and skin. Targetvolume coverage, Conformity Index (CI), Homogeneity Index (HI), and doses to OAR were compared. Results: Photon plans represented a considerably better CI and HI for the planning target volumes (PTV), compared to the electron beam plans. Regarding OAR sparing, the V1Gy and Dmean in heart and ipsilateral lung with photon beam were significantly higher than electron beam (P<0.05). Conclusion: Dosimetric analysis revealed that CI index, HI index, and PTV coverage were significantly better in photon boost plans, while OAR dosimetry conveyed a significant reduction in ipsilateral lung and heart doses with electron beam plans. [ABSTRACT FROM AUTHOR]

Background: Late cardiac toxicities caused by (particularly left-sided) breast radiotherapy (RT) are now recognized as rare but relevant sequelae, which has prompted research on risk structure identification and definition of threshold doses to heart subvolumes. The aim of the present review was to critically discuss the clinical evidence on late cardiac reactions based on dose-dependent outcome reports for mean heart doses as well as doses to cardiac substructures.Methods: A literature review was performed to examine clinical evidence on radiation-induced heart toxicities. Mean heart doses and doses to cardiac substructures were focused upon based on dose-dependent outcome reports. Furthermore, an overview of radiation techniques for heart protection is given and non-radiotherapeutic aspects of cardiotoxicity in the multimodal setting of breast cancer treatment are discussed.Results: Based on available findings, the DEGRO breast cancer expert panel recommends the following constraints: mean heart dose <2.5 Gy; DmeanLV (mean dose left ventricle) < 3 Gy; V5LV (volume of LV receiving ≥5 Gy) < 17%; V23LV (volume of LV receiving ≥23 Gy) < 5%; DmeanLAD (mean dose left descending artery) < 10 Gy; V30LAD (volume of LAD receiving ≥30 Gy) < 2%; V40LAD (volume of LAD receiving ≥40 Gy) < 1%.Conclusion: In addition to mean heart dose, breast cancer RT treatment planning should also include constraints for cardiac subvolumes such as LV and LAD. The given constraints serve as a clinicians' aid for ensuring adequate heart protection. The individual decision between sufficient protection of cardiac structures versus optimal target volume coverage remains in the physician's hand. The risk of breast cancer-specific mortality and a patient's cardiac risk factors must be individually weighed up against the risk of radiation-induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

Abstract This study aimed to investigate the effect of body habitus on supraclavicular (SC) dose-volume histogram (DVH) parameters among breast cancer patients according to 3 different techniques. Three SC irradiation plans were generated for 24 postoperative breast cancer patients: (1) direct antero-posterior field only (1fieldP), with dose prescribed to a 3-cm depth; (2) 3-cm depth plan (3cmP) using an antero-posterior field plus a posterior boost with the dose prescription defined to 3 cm; and (3) optimized plan (OptP) similar to 3cmP, with dose prescribed depending on the anatomy. The OptP plans had the least variation in DVH parameters with body habitus; 3cmP plans were the most varied. Conformity index among normal weight patients were 0.73, 0.78, and 0.87 (p = 0.02) and 0.61, 0.6, and 0.82 among overweight-obese patients for 1fieldP, 3cmP, and OptP, respectively (p < 0.001). V 95% of the planning target volume among normal weight patients were 72.63%, 78.03%, and 87.18% for 1fieldP, 3cmP, and OptP, respectively (p = 0.02). The corresponding values among overweight-obese patients were 60.5%, 59.62%, and 81.62%, respectively (p = 0.001). Fixed depth dose prescriptions caused greater SC under dose than plans optimized according to patient's anatomy. [ABSTRACT FROM AUTHOR]

The article presents a commentary on helical tomotherapy for patients presented with implant breast reconstruction in case of adjuvant breast cancer radiotherapy. Topics include patients presented with implant breast reconstruction (IBR) treated by intensity-modulated radiotherapy (IMRT) using helical tomotherapy; and indication of radiotherapy and fields were previously defined in multi-disciplinary meeting and in accordance with our institution's standard protocols.

For decades, postmastectomy radiotherapy (PMRT) has been recommended for node positive [N(+)] breast cancer patients; nevertheless, the beneficial effect of PMRT for treatment of node negative [N(-)] disease remains under discussion. Nowadays, the biology of breast cancer and the risk factors (RFs) for locoregional failure (LRF) must be included in the decision on whether or not to carry out PMRT. For these reasons, the present review aims to evaluate the rationale use of PMRT in N(-) patients and discuss which subgroups may further benefit from the treatment in present times where the decision must be personalised, according to the RFs of locoregional recurrence (LRR). To perform the analysis, we ponder that LRR of over 10% should be considered unacceptable due to the fact that LRRs generate great morbidity in patients. For this purpose, we consider that routine RT in these patients is not recommended, although there are subgroups of patients with high LRR, in which PMRT could be beneficial. [ABSTRACT FROM AUTHOR]

Purpose To train and evaluate a very deep dilated residual network (DD-ResNet) for fast and consistent auto-segmentation of the clinical target volume (CTV) for breast cancer (BC) radiotherapy with big data. Methods DD-ResNet was an end-to-end model enabling fast training and testing. We used big data comprising 800 patients who underwent breast-conserving therapy for evaluation. The CTV were validated by experienced radiation oncologists. We performed a fivefold cross-validation to test the performance of the model. The segmentation accuracy was quantified by the Dice similarity coefficient (DSC) and the Hausdorff distance (HD). The performance of the proposed model was evaluated against two different deep learning models: deep dilated convolutional neural network (DDCNN) and deep deconvolutional neural network (DDNN). Results Mean DSC values of DD-ResNet (0.91 and 0.91) were higher than the other two networks (DDCNN: 0.85 and 0.85; DDNN: 0.88 and 0.87) for both right-sided and left-sided BC. It also has smaller mean HD values of 10.5 mm and 10.7 mm compared with DDCNN (15.1 mm and 15.6 mm) and DDNN (13.5 mm and 14.1 mm). Mean segmentation time was 4 s, 21 s and 15 s per patient with DDCNN, DDNN and DD-ResNet, respectively. The DD-ResNet was also superior with regard to results in the literature. Conclusions The proposed method could segment the CTV accurately with acceptable time consumption. It was invariant to the body size and shape of patients and could improve the consistency of target delineation and streamline radiotherapy workflows. [ABSTRACT FROM AUTHOR]

There have been significant technological and technical advances in radiotherapy over the last 20 years. This paper presents the pertinent advances and examines their application in contemporary breast cancer (BC) radiotherapy, particularly for reducing the long-term toxicity, using intensity-modulated radiation therapy, image-guided radiation therapy, and management of breathing motion. These modern technologies and techniques enable precise delivery of a highly conformal radiation dose distribution to the target volume in real-time, to optimise tumour control, and minimise treatment toxicity. They have been used for the treatment of BC in selected centres around the world. Although there is insufficient high-level evidence to support their routine application in BC at present, implementation of these technologies has been shown to be feasible, and could result in clinically meaningful long-term benefits for selected patients with BC.

Objectives Atlas-based automatic segmentation (ABAS) addresses the challenges of accuracy and reliability in manual segmentation. We aim to evaluate the contribution of specific-purpose in ABAS of breast cancer (BC) patients with respect to generic-purpose libraries. Materials and methods One generic-purpose and 9 specific-purpose libraries, stratified according to type of surgery and size of thorax circumference, were obtained from the computed tomography of 200 BC patients. Keywords about contralateral breast volume and presence of breast expander/prostheses were recorded. ABAS was validated on 47 independent patients, considering manual segmentation from scratch as reference. Five ABAS datasets were obtained, testing single-ABAS and multi-ABAS with simultaneous truth and performance level estimation (STAPLE). Center of mass distance (CMD), average Hausdorff distance (AHD) and Dice similarity coefficient (DSC) between corresponding ABAS and manual structures were evaluated and statistically significant differences between different surgeries, structures and ABAS strategies were investigated. Results Statistically significant differences between patients who underwent different surgery were found, with superior results for conservative-surgery group, and between different structures were observed: ABAS of heart, lungs, kidneys and liver was satisfactory (median values: CMD<2 mm, DSC≥0.80, AHD<1.5 mm), whereas chest wall, breast and spinal cord obtained moderate performance (median values: 2 mm ≤ CMD<5 mm, 0.60 ≤ DSC<0.80, 1.5 mm ≤ AHD<4 mm) and esophagus, stomach, brachial plexus and supraclavicular nodes obtained poor performance (median CMD≥5 mm, DSC<0.60, AHD≥4 mm). The application of STAPLE algorithm generally yields higher performance and the use of keywords improves results for breast ABAS. Conclusion The homogeneity in the selection of atlases based on multiple anatomical and clinical features and the use of specific-purpose libraries can improve ABAS performance with respect to generic-purpose libraries. [ABSTRACT FROM AUTHOR]