Setup margins based on the inter- and intrafractional setup error of left-sided breast cancer radiotherapy using deep inspiration breath-hold technique (DIBH) and surface guided radiotherapy (SGRT).

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.

Three-dimensional conformal radiotherapy (3D-CRT) vs. volumetric modulated arc therapy (VMAT) in deep inspiration breath-hold (DIBH) technique in left-sided breast cancer patients-comparative analysis of dose distribution and estimation of projected secondary cancer risk.

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.

Hybrid planning techniques for early-stage left-sided breast cancer: dose distribution analysis and estimation of projected secondary cancer-relative risk.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Anxiety and depression in patients with breast cancer undergoing radiotherapy: the role of intelligence, life history, and social support-preliminary results from a monocentric analysis.

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.

Estimating the second primary cancer risk due to proton therapy compared to hybrid IMRT for left sided breast cancer.

BACKGROUND AND PURPOSE: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Estimating long-term health risks after breast cancer radiotherapy: merging evidence from low and high doses.

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.

A historical literature review on the role of posterior axillary boost field in the axillary lymph node coverage and development of lymphedema following regional nodal irradiation in breast cancer.

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.

Provider delay in treatment initiation and its influence on survival outcomes in women with operable breast cancer.

AIM: 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). BACKGROUND: Limited medical infrastructure and a lack of cancer prevention awareness in low- and middle-income countries have caused high BrCr incidence and mortality rates. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Heart toxicity from breast cancer radiotherapy : Current findings, assessment, and prevention.

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.

Estimated Doses to the Heart, Lungs and Oesophagus and Risks From Typical UK Radiotherapy for Early Breast Cancer During 2015-2023.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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%.

New technique and application of truncated CBCT processing in adaptive radiotherapy for breast cancer.

OBJECTIVE: A generative adversarial network (TCBCTNet) was proposed to generate synthetic computed tomography (sCT) from truncated low-dose cone-beam computed tomography (CBCT) and planning CT (pCT). The sCT was applied to the dose calculation of radiotherapy for patients with breast cancer. METHODS: The low-dose CBCT and pCT images of 80 female thoracic patients were used for training. The CBCT, pCT, and replanning CT (rCT) images of 20 thoracic patients and 20 patients with breast cancer were used for testing. All patients were fixed in the same posture with a vacuum pad. The CBCT images were scanned under the Fast Chest M20 protocol with a 50% reduction in projection frames compared with the standard Chest M20 protocol. Rigid registration was performed between pCT and CBCT, and deformation registration was performed between rCT and CBCT. In the training stage of the TCBCTNet, truncated CBCT images obtained from complete CBCT images by simulation were used. The input of the CBCT→CT generator was truncated CBCT and pCT, and TCBCTNet was applied to patients with breast cancer after training. The accuracy of the sCT was evaluated by anatomy and dosimetry and compared with the generative adversarial network with UNet and ResNet as the generators (named as UnetGAN, ResGAN). RESULTS: The three models could improve the image quality of CBCT and reduce the scattering artifacts while preserving the anatomical geometry of CBCT. For the chest test set, TCBCTNet achieved the best mean absolute error (MAE, 21.18±3.76 HU), better than 23.06±3.90 HU in UnetGAN and 22.47±3.57 HU in ResGAN. When applied to patients with breast cancer, TCBCTNet performance decreased, and MAE was 25.34±6.09 HU. Compared with rCT, sCT by TCBCTNet showed consistent dose distribution and subtle absolute dose differences between the target and the organ at risk. The 3D gamma pass rates were 98.98%±0.64% and 99.69%±0.22% at 2 mm/2% and 3 mm/3%, respectively. Ablation experiments confirmed that pCT and content loss played important roles in TCBCTNet. CONCLUSIONS: High-quality sCT images could be synthesized from truncated low-dose CBCT and pCT by using the proposed TCBCTNet model. In addition, sCT could be used to accurately calculate the dose distribution for patients with breast cancer.

Comparative Study of Hypo-Fractionated Radiotherapy Versus Conventional Radiotherapy in Breast Cancer.

BACKGROUND: Breast cancer is the most commonly diagnosed cancer causing death among females worldwide. Radiotherapy after lumpectomy/mastectomy in breast cancer cases is a successful treatment modality taking five weeks to complete. The aim of the present study is to compare the effectiveness of hypo-fractionated radiotherapy in breast cancer patients with conventional radiotherapy with respect to outcome and toxicity. METHODS: Sixty patients were randomly divided equally into a conventional group, Group A (dose: 50 Gy in 25 fractions), and a hypo-fractionated short-course radiotherapy group, Group B (dose: 40 Gy in 16 fractions). After thorough clinical and laboratory examination of all patients, the disease status was assessed prior to radiotherapy and three and six months after completion of radiotherapy. The cardiopulmonary function was assessed using echocardiography and pulmonary function tests prior to the procedure. The assessment of the development of toxicity (dysphagia, skin, lung, and lymphedema) was done during every clinical visit. RESULTS: The mean age of patients was 53.28 ± 9.73 years in Group A, and 55.67 ± 10.41 years in Group B (p=0.82). The right breast was involved in 13 (43.4%) patients in Group A and 14 (46.6%) in Group B, and the left breast was involved n 17 (56.6%) patients in Group A and 16 (53.4%) in Group B (p=0.81). Most of the patients were post-menopausal; 24 (80%) in Group A and 25 (83.4%) in Group B (p=0.91). Eleven (36.6%) patients were of stage T2N1M0 in both groups. However, no statistical difference was observed between the groups in the TNM (tumor, node, and metastasis) staging using the AJCC (American Joint Committee on Cancer) criteria (p=0.26). On comparing the responses in Group A and Group B, no significant difference was observed in either of the groups from immediate post-treatment to the 12-month follow-up period (p=0.53 and p=0.64, respectively). CONCLUSION: Hypo-fractionated radiotherapy is as effective as conventional radiotherapy and can be used as an alternative method for treatment following breast cancer surgery.

TROG 14.04: Multicentre Study of Feasibility and Impact on Anxiety of DIBH in Breast Cancer Patients.

AIMS: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Comparison of visibility of iodinated hydrogel and gadolinium-modified hyaluronic acid spacer gels on computed tomography and onboard imaging.

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.

Cost-effectiveness of Post-Mastectomy Radiotherapy (PMRT) for breast cancer in India: An economic modelling study.

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.

Comparison of normal tissue doses in deep inspiration breath-hold and free breathing methods for radiotherapy of left-sided breast cancer using 4D-XCAT digital phantom.

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.

Different meaning of the mean heart dose between 3D-CRT and IMRT for breast cancer radiotherapy.

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.

Toxicity of Hypofractionated Whole Breast Radiotherapy Without Boost and Timescale of Late Skin Responses in a Large Cohort of Early-Stage Breast Cancer Patients.

AIM: To report toxicity of hypofractionated whole-breast radiotherapy in a large cohort of early-stage breast cancer (BCaients. MATERIALS AND METHODS: From 02/2009-05/2017, 1325 consecutive BCa patients were treated with 40.05 Gy/15 fractions, without boost. Median age was 62 (IQR:51.1-70.5) years. Chemotherapy was prescribed for 28% of patients, hormonal therapy for 80.3%, monoclonal antibodies for 8.2%. RESULTS: Median follow-up was 72.4 (IQR: 44.6-104.1) months. Acute RTOG toxicity was: 69.8% Grade (G) 1, 14.3% G2 and 1.7% G3. Late SOMA-LENT toxicities were: edema-hyperpigmentation (E-H): G1 28.67%, G2 4.41%, G3 0.15%; fibrosis-atrophy-telangiectasia-pain (F-A-T-P): G1 14.6%, G2 3.2%, G3 0.8%, G4 0.1%. Median time to first occurrence was 6 and 18 months, respectively. Aesthetic result after surgery was excellent in 28.7%, good in 41.5%, acceptable in 20.3% and poor in 9.5% of patients. Change in breast appearance after radiotherapy was mild in 6.9%, moderate in 2.3% and marked in 1.3% of patients. Concomitant chemotherapy, obesity, smoking, use of bolus and planning target volume (PTV) were associated with higher acute toxicity. Patients ≥55 years old were less likely to experience acute toxicity. PTV and acute G2 toxicity were associated with ≥G2 E-H. PTV, concomitant chemotherapy, hypertension and ≥G2 acute toxicity were associated with increased risk of F-A-T-P. CONCLUSION: Hypofractionated whole-breast radiotherapy without boost demonstrated mild acute and late toxicity in a large cohort of consecutive patients. Moderate and marked changes in breast appearance were registered for 3.6% of patients and occurred between 18 to 42 months.

Improving deformable image registration with point metric and masking technique for postoperative breast cancer radiotherapy.

BACKGROUND: Deformable image registration (DIR) is increasingly used for target volume definition in radiotherapy. However, this method is challenging for postoperative breast cancer patients due to the large deformations and non-correspondence caused by tumor resection and clip insertion. In this study, an improved B-splines based DIR method was developed to address this issue for higher registration accuracy. METHODS: The conventional B-splines based DIR method was improved with the introduction of point metric and masking technique. The point metric minimizes the distance between 2 point sets with known correspondence for regularization of intensity-based B-splines registration. The masking technique reduces the influence of non-corresponding regions in breast computed tomography (CT) images. Two sets of CT images before and after breast surgery were used for image registration. One set was the diagnostic CT image acquired before surgery, and another set was the planning CT image acquired after surgery for breast cancer radiotherapy. A total of 26 sets of CT images from 13 patients were collected retrospectively for the test. The improved DIR method's registration accuracy was evaluated by target registration error (TRE), the Jacobian determinant, and visual assessment. RESULTS: For soft tissue, the difference in the median TRE between the improved DIR method and the conventional DIR method was statistically significant (2.27 vs. 5.88, P<0.05). The Jacobian determinant of the deformation field was positive for all patients. For visual assessment, the improved DIR method with point metric achieved better matching for soft tissue. CONCLUSIONS: The improved DIR method's registration accuracy was higher than the conventional DIR method based on the preliminary results. With point metric and masking technique, the influence of large deformations and non-correspondence on registration between pre- and post-operative CT images can be effectively reduced. Therefore, this method provides a feasible way for target volume definition in postoperative breast cancer radiotherapy treatment planning.