Right-sided Breast Cancer Patients Research Articles

Determinants of radiation dose to immune cells during breast radiotherapy.

The immune system has been identified as an organ at risk in esophageal and lung cancers. However, the dosimetric impact of radiotherapy on immune system exposure in patients treated for breast cancer has never been studied. Amonocentric retrospective dosimetric study included 163 patients treated at the Institut Curie (Paris, France) between 2010 and 2016 with locoregional helical tomotherapy after conservative surgery or total mastectomy. The effective dose to the immune system (EDIC) was calculated based on diverse dosimetric parameters. The clinical and volumetric determinants of EDIC in adjuvant radiotherapy of breast cancer were analyzed. The median EDIC for the population was 4.23 Gy, ranging from 1.82 to 6.19Gy. Right-sided radiotherapy and regional lymph node irradiation were associated with significantly higher EDIC in univariate (4.38 Gy vs. 3.94 Gy, p < 0.01, and 4.27 Gy vs. 3.44 Gy, p < 0.01, respectively) and multivariate analyses (p < 0.01 and p < 0.01). Liver overexposure was the main contributor to EDIC increase in right-sided breast cancer patients (+0.38 Gy [95%CI: +0.30; +0.46]), while the integral total dose increase was the main contributor to EDIC increase in cases of regional node irradiation (+0.63 Gy [95%CI: +0.42; +0.85]). The EDIC score during adjuvant radiotherapy after breast cancer was statistically significantly higher in the case of right-sided radiotherapy and regional lymph node irradiation. Liver irradiation is the main contributor to immune system exposure in adjuvant irradiation of right-sided breast cancer. Populations in which an association between EDIC and survival would exist have yet to be identified but could potentially include patients treated for triple-negative breast cancer with apoor response to neoadjuvant chemoimmunotherapy.

7 Flexible probabilistic methods to unlock the clinical potential of liquid biopsy sampling

OBJECTIVES/GOALS: Decoding the origins of cell-free DNA (cfDNA) released from dying cells in a liquid biopsy sample (e.g. blood) offers the potential to provide insight into the dynamic, organism-wide changes reflective of health and disease. Thus, making cfDNA an ideal target for serial, minimally invasive monitoring of disease-related changes. METHODS/STUDY POPULATION: We develop a probabilistic method that leverages the co-regulation of neighboring CpG sites on individual methylome-wide sequencing (WGBS) reads to more flexibly model cell-specific methylation compared to prior methods that focus on the methylation rate of a single CpG site. We then extend our cross-sectional model to account for sequential sampling within the same subject. The increased sampling frequency is critical to identifying the evolutionary dynamics of disease progression influencing treatment response and resistance, and disease recurrence. We utilize Bayesian inference techniques to model patient-specific longitudinal profiles of cell-type turnover in simulated serial samples. RESULTS/ANTICIPATED RESULTS: We found our model more effective at capturing a range of methylation patterns on cfDNA fragments with lower Root Mean Square Error across simulations compared to a single CpG model. We apply our model to detect significant (p &lt; 0.05, Friedman’s test) increases in cellular contributions from lung and cardiac tissue in breast cancer patients (n=15) undergoing radiation therapy compared to baseline. We also identify signals of radiation induced toxicity to the liver in right-sided breast cancer patients (n=8) receiving radiation treatment compared to left-sided breast cancer patients (n=7). Finally, we show our extended model results in more efficient estimates of simulated cell-type turnover profiles compared to analyzing serial samples cross-sectionally, ignoring the longitudinal nature of the data. DISCUSSION/SIGNIFICANCE: Here we address an unmet need in developing novel statistical methodologies to decode the origins of methylated cfDNA obtained from liquid biopsy samples. We demonstrate the far-ranging clinical utility of serial liquid biopsy sampling to complement and advance the standards of clinical care in oncology and other pathologies.

103 Predicting Lung Dose for Right-Sided Breast Cancer Patients with Traditional Machine Learning and Neural Networks

103 Predicting Lung Dose for Right-Sided Breast Cancer Patients with Traditional Machine Learning and Neural Networks

Integrating subvolume dose and myocardial perfusion imaging parameters to assess the impact of radiation therapy on heart function in breast cancer patients: A comparative analysis between left- and right-sided breast cancer.

This study aimed to utilize an innovative method of integrating the 20 subvolume dose of left ventricle and the Tl-201 single photon emission computed tomography (SPECT) with myocardial perfusion imaging (MPI) parameters in patients with left- and right-sided breast cancer after radiation therapy. Female patients with breast cancer underwent SPECT MPI before commencing radiotherapy and 12 months later were enrolled from January 2014 to December 2018. The images of CT simulation and SPECT MPI were integrated into the treatment planning system. The differences of doses and parameters of MPI in all cardiac subvolumes between left- and right-sided breast cancer patients were analyzed. Patients with left-sided breast cancer (n = 61) received a higher radiation dose to the heart, left ventricular, and its territories and subvolumes, compared to patients with right-sided breast cancer (n = 19). The 20-segment analysis also showed statistically significant disparities in the average radiation doses received by the two groups. In different coronary artery territories, the end-diastolic perfusion and end-systolic perfusion showed a decrease in both sides, with no significant differences. However, the wall motion and wall thickening showed a significant decline in subregions within the left- and right-sided coronary artery territories. This study demonstrates an innovative integrated method combining the left ventricular 20 regional doses with SPECT MPI which shows that left-sided breast cancer patients receive a higher subvolume dose than right-sided breast cancer patients. Further research is needed to confirm the potential impact on heart function after radiotherapy on both sides.

The effect of breath-hold technique on conformal and intensity modulated radiotherapy techniques at right breast cancer radiotherapy including internal mammarian field

Background/Aim: Significantly lower heart doses can be achieved by breath-hold technique at left-sided breast cancer radiotherapy (RT). We see high doses at organs at risk such as lung, heart, and contralateral breast during right-sided breast cancer RT planning especially in the presence of RT indication for mammaria interna (MI) lymph nodes. This study compared RT-planning methods that are conformal with intensity-modulated RT (IMRT) with breath holding and free breathing for right-sided breast cancer RT including full axillary and MI lymph node fields. Methods: Computed tomography (CT) simulations were performed using free-breath (FB) and breath-hold (BH) methods in 10 patients with right-sided breast cancer. A total of 40 RT treatment plans were calculated. Right-sided breast, level 1-2-3 axillary regions, and MI regions served for the target-planning volume. Left-sided breast, heart, as well as right-sided and left lungs were contoured as critical organs according to the atlas of the "Radiation Therapy Oncology Group." We used a Varian Eclipse v.13 for treatment planning. Conformal “FieldinField” RT (FinFRT) and dynamic IMRT (dIMRT) planning were performed separately for each patient over breath-hold and free-breath images. For PTV, 50 Gy was prescribed in 25 fractions and optimized such that the planned target volume (PTV) remained between 95% and 110% of the dose. The mean and maximum doses of the heart, V5 and V20 of the lungs, as well as V95 doses for MI were recorded. Statistical analyses were performed with SPSS version 22, and a paired t-test was used for comparison. Results: Four treatment plans (FB FinFRT, BH FinFRT, FB dIMRT, BH dIMRT) were made separately for 10 patients. For comparison, common FB FinFRT plans were accepted as the baseline plan. As expected, there were no significant differences in PTV coverage. The mean dose received by 95% of the MI volume was between 42.27 Gy and 42.4 Gy. For the maximum heart dose, the breath hold technique had no significant effect on plans. The lowest average maximum heart dose was seen in the BH FinFRT group. Mean heart doses are between 1.28 Gy – 4.85 Gy. There was no significance between BH FinFRT and FB FinFRT plan (P=0.504), and there was a significant difference for heart mean dose versus dIMRT plans (P=0.001). The mean V20 of the lungs ranged from 11.9 to 17.8. There was a significant decrease in V20 with BH or FB dIMRT plans (P=0.001). There was no difference between BH FinFRT (P=0.138). On the contrary, lung V5 values were significantly higher in dIMRT plans, and the lowest mean V5 value was seen in BH FinFRT plan. Conclusion: With the BH method, lower doses (but not significantly lower doses) were obtained in critical organ doses. There was a significant decrease with FinFRT plans in terms of heart mean and maximum dose and lung V5 percentages. The dIMRT plans were significant only in lung V20 percentages. When planning RT, we recommend evaluating all treatment techniques individually for right-sided breast cancer patients to obtain lower doses in critical organs.

Effects of low-to-moderate doses of X-rays on the cardiac rhythm via the sympathetic nervous system in female mice

Radiotherapy is one of the common therapeutic approaches in the treatment of breast cancer, with the heart inevitably being exposed to ionizing radiation which may cause late cardiac pathologies. Our recent study revealed that right atrium irradiation of right-sided breast cancer patients is associated with the development of cardiac diseases such as heart failure, arrhythmias, and conduction disorders. The aim of this project is to examine the effect of low to moderate doses of X-rays on the development of late cardiac pathologies. We specifically studied the alterations in the cardiac sympathetic nervous system which is located in potentially arrhythmogenic structures of the sinoatrial and atrioventricular nodes. Female C57Bl/6J mice were exposed to X-rays irradiation targeted to top, bottom or whole heart, such that different cardiac nodes were exposed. To examine the presence of a threshold in a dose-response for cardiac rhythm pathology, as assessed by ultrasound examinations, mice were exposed to doses ranging from 0.25 to 2 Gy. Molecular and cellular mechanisms involved in these cardiac disorders at early (24-hours) and late (60-weeks) time points post-irradiation were studied. At the functional level, our Doppler echography data show the presence of an alteration of cardiac function with the occurrence of arrhythmic events at 60-weeks post-irradiation in all irradiated animals, specifically in top heart irradiation. To confirm these results, we will also use transesophageal atrial stimulation (10 Hz during 3 sec) to assess supraventricular arrhythmias. At the molecular level, we focused on proteins involved in cardiac conduction system and in sympathetic innervation patterning 24-hours post-irradiation. Our Western Blot results show a significant increase of Connexin 40 (P = 0.02), Connexin 43 (P = 0.02), Tyrosine Hydroxylase (P = 0.04), and b3-Tubulin (P = 0.03) protein levels in whole heart irradiated animals. Altogether, our preliminary results showed modifications of cardiac function 60-weeks post-irradiation with the development of cardiac rhythm disorders and molecular alterations of cardiac conduction and sympathetic nervous system already present 24-hours post-irradiation.

SGRT-based DIBH radiotherapy practice for right-sided breast cancer combined with RNI: A retrospective study on dosimetry and setup accuracy.

We retrospectively studied the dosimetry and setup accuracy of deep inspiration breath-hold (DIBH) radiotherapy in right-sided breast cancer patients with regional nodal irradiation (RNI) who had completed treatment based on surface-guided radiotherapy (SGRT) technology by Sentinel/Catalyst system, aiming to clarify the clinical application value and related issues. Dosimetric indicators of four organs at risk (OARs), namely the heart, right coronary artery (RCA), right lung, and liver, were compared on the premise that the planning target volume met dose-volume prescription requirements. Meanwhile, the patients were divided into the edge of the xiphoid process (EXP), sternum middle (SM), and left breast wall (LBW) groups according to different positions of respiratory gating primary points. The CBCT setup error data of the three groups were contrasted for the treatment accuracy study, and the effects of different gating window heights on the right lung volume increases were compared among the three groups. Compared with free breath (FB), DIBH reduced the maximum dose of heart and RCA by 739.3±571.2 cGy and 509.8±403.8 cGy, respectively (p<0.05). The liver changed the most in terms of the mean dose (916.9±318.9 cGy to 281.2±150.3 cGy, p<0.05). The setup error of the EXP group in the anterior-posterior (AP) direction was 3.6±4.5mm, which is the highest among the three groups. The right lung volume increases in the EXP, SM, and LBW groups were 72.3%, 69.9%, and 67.2%, respectively (p=0.08), and the corresponding breath-holding heights were 13.5±3.7mm, 10.3±2.4mm, and 9.6±2.8mm, respectively (p<0.05). SGRT-based DIBH radiotherapy can better protect the four OARs of right-sided breast cancer patients with RNI. Different respiratory gating primary points have different setup accuracy and breath-hold height.

35 Novel statistical methods to unlock the clinical potential of liquid biopsy sampling

OBJECTIVES/GOALS: Decoding the origins of cell-free DNA (cfDNA) released from dying cells in a liquid biopsy sample (e.g. blood) can provide insight into the dynamic, organism-wide changes reflective of health and disease state. Making cfDNA an ideal target for genomic monitoring of disease-related changes. METHODS/STUDY POPULATION: Methylome-wide sequencing (WGBS) data present unique statistical challenges. To this end, we developed a novel statistical method using an Expectation-Maximization algorithm to decode the cellular origins of cfDNA fragments in liquid biopsies. Our flexible, probabilistic method leverages the co-regulation of neighboring CpG sites on the individual sequencing read to facilitate tissue of origin analysis, as opposed to prior methods that focus on the methylation rate of a single CpG site. We assess the performance of our model in various simulated settings and apply our model to an important clinical example in which we are able to detect early off-target tissue damage from radiation therapy via minimally invasive blood draws. RESULTS/ANTICIPATED RESULTS: We found our model more effective at capturing the range of biologically plausible methylation patterns on cfDNA read fragments compared to prior models that use single CpG sites. We also show our model is robust to high levels of noise inherent with WGBS data. We demonstrate the accuracy of cell-type proportion estimation on in-silico mixed cfDNA samples from real WGBS data. Finally, we use our model in a clinical application. We detect significant (p &lt; 0.05) increases in cellular contributions from lung and cardiac tissue in breast cancer patients (n=15) undergoing radiation therapy compared to baseline. We also detect novel signals of radiation induced toxicity to the liver in right-sided breast cancer patients (n=8) receiving radiation treatment compared to matched left-sided breast cancer patients (n=7). DISCUSSION/SIGNIFICANCE: Here we address an unmet need in developing novel statistical methodologies that can handle the unique complexities of methylated cfDNA obtained from liquid biopsy samples. We also demonstrate the far-ranging clinical utility of serial liquid biopsy sampling to complement and advance standards of clinical care in oncology and other pathologies.

Dosimetric evaluation of VMAT and helical tomotherapy techniques comparing conventional volumes with clinical target volumes based on new ESTRO ACROP post-mastectomy with immediate implant reconstruction contouring guidelines

BackgroundThe ESTRO-ACROP Consensus Guideline (EACG) recommends implant excluded clinical target volume (CTVp) definitions for post-mastectomy radiation therapy after implant-based immediate breast reconstruction (IBR). The purpose of this study is to investigate the effectiveness of Helical Tomotherapy (HTp) and Volumetric Modulated Arc Therapy (VMATp) treatment techniques in terms of CTVp coverage and reduced organ at risk (OAR), normal tissue and implant doses when CTVp was used for treatment planning as the target structure instead of conventional CTV.MethodsEight left-sided and eight right-sided breast cancer patients who underwent IBR after mastectomy were included in this study. Planning CT data sets were acquired during free breathing and patients were treated with HT technique targeted to conventional CTV. Retrospectively, CTVp was delineated based on EACG by the same radiation oncologist, and treatment plans with HTp and VMATp techniques were generated based on CTVp. For each patient, relevant dosimetric parameters were obtained from three different treatment plans.ResultsThere was no statistically significant difference on target coverage in terms of, PTVp-D95, PTVp-Vpres, homogeneity index (p > 0.05) between HTp and VMATp plans. But, the conformity numbers were significantly higher (HTp vs VMATp, 0.69 ± 0.15 vs 0.79 ± 0.12) for VMATp (Z = − 2.17, p = 0.030). While HTp significantly lowered Dmax and Dmean for LAD (LAD-Dmax: χ2 = 12.25, p = 0.002 and LAD-Dmean: χ2 = 12.30, p = 0.002), neither HTp nor VMATp could reduce maximum and mean dose to heart (p > 0.05). Furthermore, heart volume receiving 5 Gy was significantly higher for VMATp when compared to HTp (21.2 ± 9.8 vs 42.7 ± 24.8, p: 0.004). Both techniques succeeded in reducing the mean dose to implant (HTp vs HT, p < 0.001; VMATp vs HT, p < 0.001; VMATp vs HTp, p = 0.005).ConclusionBoth HTp and VMATp techniques succeeded to obtain conformal and homogeneous dose distributions within CTVp while reducing the mean implant dose. HTp was found to be superior to VMATp with regards to lowering all OAR doses except for CB.

Association Between Cardiac Radiation Exposure and the Risk of Arrhythmia in Breast Cancer Patients Treated With Radiotherapy: A Case-Control Study.

BackgroundPrevious studies suggested that radiation therapy (RT) for breast cancer (BC) can induce cardiac arrhythmias and conduction disorders. However, the association with mean heart dose and specific cardiac substructures doses was less studied.Materials and MethodsWe conducted a nested case–control study based on French BC patients, enrolled in the European MEDIRAD-BRACE study (https://clinicaltrials.gov, Identifier: NCT03211442), who underwent three-dimensional conformal radiation therapy (3D-CRT) between 2009 and 2013 and were retrospectively followed until 2019. Cases were incident cases of cardiac arrhythmia. Controls without arrhythmia were selected with propensity-scored matching by age, duration of follow-up, chemotherapy, hypertension, and diabetes (ratio 1:4 or 5). Doses to the whole heart (WH), left and right atria (LA and RA), and left and right ventricles (LV and RV) were obtained after delineation with multi-atlas-based automatic segmentation.ResultsThe study included 116 patients (21 cases and 95 controls). Mean age at RT was 64 ± 10 years, mean follow-up was 7.0 ± 1.3 years, and mean interval from RT to arrhythmia was 4.3 ± 2.1 years. None of the results on association between arrhythmia and cardiac doses reached statistical significance. However, the proportion of right-sided BC was higher among patients with arrhythmia than among controls (57% vs. 51%, OR = 1.18, p = 0.73). Neither mean WH dose, nor LV, RV, and LA doses were associated with an increased risk of arrhythmia (OR = 1.00, p > 0.90). In contrast, the RA dose was slightly higher for cases compared to controls [interquartile range (0.61–1.46 Gy) vs. (0.49–1.31 Gy), p = 0.44], and a non-significant trend toward a potentially higher risk of arrhythmia with increasing RA dose was observed (OR = 1.19, p = 0.60). Subanalysis according to BC laterality showed that the association with RA dose was reinforced specifically for left-sided BC (OR = 1.76, p = 0.75), while for right-sided BC, the ratio of mean RA/WH doses may better predict arrhythmia (OR = 2.39, p = 0.35).ConclusionDespite non-significant results, our exploratory investigation on BC patients treated with RT is the first study to suggest that right-sided BC patients and the right atrium irradiation may require special attention regarding the risk of cardiac arrhythmia and conduction disorders. Further studies are needed to expand on this topic.

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

AimsThe 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 methodsThe 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. ResultsBetween 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. ConclusionAlthough 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.

A semi-automatic planning technique for whole breast irradiation with tangential IMRT fields

PurposeTo implement a semi-automatic planning technique for whole breast irradiation with two tangential IMRT fields and to test the produced dose distribution against clinical 3DCRT plans, for introducing the technique in clinical practice. MethodsThe Auto-Planning module of the Pinnacle3 (Philips) treatment planning system was used for generating a Treatment Technique on left-sided breast cancer patients treated in free breathing or in deep inspiration breath hold (DIBH) and to right-sided breast cancer patients. The technique was evaluated against 3DCRT clinical plans in terms of dosimetric plan parameters. Plan robustness toward patient displacements was assessed on a subset of patients by inducing shifts to the isocenter. ResultsA statistically significant improvement in target coverage and dose homogeneity was observed for autoIMRT. No statistically significant differences were observed for ipsilateral organs, except for the ipsilateral lung in left DIBH, where slightly lower Dmean and V18% are registered for autoIMRT. Slightly higher Dmean doses (although far below the constraints) to contralateral organs were observed for autoIMRT plans.AutoIMRT plans were shown to be as robust as 3DCRT plans toward isocenter shifts, with a maximum decrease in CTV coverage of −2.2% and −2.1% for autoIMRT and 3DCRT, respectively. Average planning times were 40 min for 3DCRT and 6 min for IMRT plans. ConclusionsThe developed autoIMRT technique was proven to be advantageous for target coverage and homogeneity and sufficiently robust towards isocenter displacements. The use of automated planning consistently reduces the planning workload with improvements in plan quality.

Clinical Implications of Geometric and Dosimetric Uncertainties Due to Inter- and Intra-Fractional Movement During Volumetric Modulated Arc Therapy for Breast Cancer Patients

Compared to conventional radiotherapy (RT) techniques, modern RT with fewer fractions and smaller target volumes requires higher accuracy. This study evaluated the necessity of pre-treatment and intra-fractional cone-beam computed tomography (CBCT) by analyzing inter- and intra-fractional CBCT images of breast cancer patients receiving RT.From 57 patients, 1,206 pre-treatment CBCT and 1,067 intra-fractional CBCT images were collected. After positioning the patient according to the three skin markers drawn during simulation, pre-treatment CBCT images were acquired. During partial-arc volumetric modulated arc therapy, a simultaneous intra-fractional CBCT scan was taken as the gantry rotated around the patient. The change in position between simulation and the actual position of the patient before and during RT was assessed according to the differences in x-, y-, and z-axes. After the difference in each axis was measured, the absolute distance between two CT images was measured. Changes in dosimetric parameters were evaluated in selected patients with extreme intra-fractional movement.For right-sided breast cancer patients, left-sided breast cancer patients treated using deep-inspiration breath hold, and left-sided breast cancer patients treated using continuous positive airway pressure, median inter-fractional deviations were 0.53 (range 0.06-2.98) cm, 0.66 (range 0.08-4.41) cm, and 0.69 (range 0.04-3.80) cm and median intra-fractional deviations were 0.14 (range 0.00-0.62) cm, 0.23 (range 0.02-0.96) cm, and 0.24 (0.00-1.15) cm, respectively. Modified plans reflecting large changes in intra-fractional position in 10 selected cases revealed insufficient target coverage in seven cases and more than 20-fold increase in the volume of heart receiving more than 25 Gy of radiation in two cases.Even though the intra-fractional ROM was minimal in most cases, few cases showed huge variations that could significantly affect the goal of RT; therefore, intra-fractional verification might be necessary as well as inter-fractional verification.

Investigation of clinical target volume segmentation for whole breast irradiation using three-dimensional convolutional neural networks with gradient-weighted class activation mapping.

This study aims to implement three-dimensional convolutional neural networks (3D-CNN) for clinical target volume (CTV) segmentation for whole breast irradiation and investigate the focus of 3D-CNNs during decision-making using gradient-weighted class activation mapping (Grad-CAM). A 3D-UNet CNN was adopted to conduct automatic segmentation of the CTV for breast cancer. The 3D-UNet was trained using three datasets of left-, right-, and both left- and right-sided breast cancer patients. Segmentation accuracy was evaluated using the Dice similarity coefficient (DSC). Grad-CAM was applied to trained CNNs. The DSCs for the datasets of the left-, right-, and both left- and right-sided breasts were on an average 0.88, 0.89, and 0.85, respectively. The Grad-CAM heatmaps showed that the 3D-UNet used for segmentation determined the CTV region from the target-side breast tissue and by referring to the opposite-side breast. Although the size of the dataset was limited, DSC ≥ 0.85 was achieved for the segmentation of breast CTV using the 3D-UNet. Grad-CAM indicates the applicable scope and limitations of using a CNN by indicating the focus of such networks during decision-making.

Clinical Implications of Geometric and Dosimetric Uncertainties of Inter- and Intra-Fractional Movement during Volumetric Modulated Arc Therapy for Breast Cancer Patients.

Simple SummaryRadiotherapy is an essential treatment modality for breast cancer. Compared to conventional radiotherapy techniques, modern radiotherapy with fewer fractions and smaller target volumes requires higher accuracy. Image-guidance using cone-beam computed tomography (CBCT) is one of the most common methods used for positional verification before treatment. This study reports geometric and dosimetric outcomes evaluated by analyzing CBCT images acquired before and during treatments. The positional change and internal movement of the patient were less than 1 cm in most cases without significant deviation in the dosimetric parameters of interest. However, there were cases involving extreme variation, which resulted in insufficient radiation delivered to the target areas and increased radiation exposure to adjacent normal organs. The results of the current study suggest that unexpected intra-fractional motion may occur, prompting for marginal adaptation in selected patients who are deemed to suffer from this kind of event.With the introduction of modern sophisticated radiotherapy (RT) techniques, the significance of accuracy has increased considerably. This study evaluated the necessity of pre-treatment and intra-fractional cone-beam computed tomography (CBCT) by analyzing inter- and intra-fractional CBCT images of breast cancer patients receiving RT. From 57 patients, 1206 pre-treatment CBCT and 1067 intra-fractional CBCT images were collected. Geometric movements of patients were measured quantitively in both inter- and intra-fractional CBCT, and changes in dosimetric parameters were evaluated in selected patients with extreme intra-fractional movement. For right-sided breast cancer patients, left-sided breast cancer patients treated using deep-inspiration breath hold (DIBH), and left-sided breast cancer patients treated using continuous positive airway pressure (CPAP), median inter-fractional deviations were 0.53 (range 0.06–2.98) cm, 0.66 (range 0.08–4.41) cm, and 0.69 (range 0.04–3.80) cm, and median intra-fractional deviations were 0.14 (range 0.00–0.62) cm, 0.23 (range 0.02–0.96) cm, and 0.24 (0.00–1.15) cm, respectively. Modified plans reflecting large changes in intra-fractional position in 10 selected cases revealed insufficient target coverage in seven cases and more than 20-fold increase in the volume of heart receiving at least 25 Gy in two cases. Intra-fractional verification, as well as pre-treatment verification, might be considered in patients using DIBH or CPAP.

Volumetric Modulated Arc Therapy Versus Three-Dimensional Conformal Radiotherapy for Breast Cancer Patients Treated with Regional Nodal Irradiation

Locally advanced breast cancer is often treated with adjuvant radiotherapy to the chest wall or breast and the regional nodes following surgery. Intensity-modulated radiotherapy (IMRT) can improve target coverage and spare organ at risk, but the efficacy and safety of IMRT for locally advanced breast cancer have not been clarified. We aimed to compare the dosimetric parameters and clinical outcomes between 3D-CRT and volumetric modulated arc therapy (VMAT) for breast cancer. The hypothesis is that VMAT has better target coverage without increasing toxicities. Breast cancer patients who received adjuvant radiotherapy with regional nodes irradiation between July 2016 and December 2019 were included. Patients with a right-sided disease were treated with three-dimensional conformal radiotherapy (3D-CRT), whereas patients with a left-sided disease were treated with VMAT to reduce heart dose. Patients who received bilateral radiotherapy were excluded. Radiotherapy was delivered to the chest wall or breast, and supraclavicular region with or without internal mammary nodes. A dose of 50 Gy in 25 fractions was prescribed to the reference point for 3D-CRT, and to cover 75% of the PTV for VMAT. Single full or two partial arcs with 6MV were used for VMAT. Clinical outcome and dosimetric data were collected retrospectively from medical records. Toxicities were assessed by CTCAE ver.4.0. A total of 74 consecutive patients were included in this study. Thirty-five left-sided breast cancer patients received VMAT, and 39 right-sided breast cancer patients received 3D-CRT. The median follow-up was 591 days. The median age was 50 years. Grade 2 or higher acute dermatitis were observed in 10 patients (29%) with VMAT versus 17 patients (44%) with 3D-CRT (P = 0.18). Grade 3 acute dermatitis occurred in one patient in the 3D-CRT group. Grade 2 radiation pneumonitis occurred in one patient in each group (P = 1.0). Acute radiation esophagitis occurred in 25 patients only in the VMAT group. CTV coverage (CTV V47.5Gy, D95%, D75%) was significantly better for VMAT (86%, 42 Gy, 49 Gy) compared to 3D-CRT (72%, 29 Gy, 46 Gy) (all P < 0.01). Total lung V20 Gy was lower for VMAT versus 3D-CRT (11Gy versus 13 Gy, P < 0.01), whereas total lung V5 Gy and mean dose were higher for VMAT (34 Gy and 7.8 Gy) compared to 3D-CRT (22 Gy and 6.9 Gy) (P < 0.01, 0.01). Because of the laterality, the dose to the heart and esophagus was higher in the VMAT group (P < 0.01, 0.01). Five patients experienced recurrence (two distant metastases in the VMAT group and two distant and one local and distant metastases in the 3D-CRT group). VMAT for breast radiotherapy with regional nodal irradiation had better target coverage and lower lung V20 Gy at the expense of a small increase in the lung mean dose and V5 Gy. VMAT can be safely administered with similar toxicity to 3D-CRT.

Crawl positioning improves set-up precision and patient comfort in prone whole breast irradiation

Prone positioning for whole-breast irradiation (WBI) reduces dose to organs at risk, but reduces set-up speed, precision, and comfort. We aimed to improve these problems by placing patients in prone crawl position on a newly developed crawl couch (CrC). A group of 10 right-sided breast cancer patients requiring WBI were randomized in this cross-over trial, comparing the CrC to a standard prone breastboard (BB). Laterolateral (LL), craniocaudal (CC) and anterioposterior (AP) set-up errors were evaluated with cone beam CT. Comfort, preference and set-up time (SUT) were assessed. Forty left and right-sided breast cancer patients served as a validation group. For BB versus CrC, AP, LL and CC mean patient shifts were − 0.8 ± 2.8, 0.2 ± 11.7 and − 0.6 ± 4.4 versus − 0.2 ± 3.3, − 0.8 ± 2.5 and − 1.9 ± 5.7 mm. LL shift spread was reduced significantly. Nine out of 10 patients preferred the CrC. SUT did not differ significantly. The validation group had mean patient shifts of 1.7 ± 2.9 (AP), 0.2 ± 3.6 (LL) and − 0.2 ± 3.3 (CC) mm. Mean SUT in the validation group was 1 min longer (P < 0.05) than the comparative group. Median SUT was 3 min in all groups. The CrC improved precision and comfort compared to BB. Set-up errors compare favourably to other prone-WBI trials and rival supine positioning.

Modified Technique of Chemoport Insertion in Breast Cancer Patient for Administration of Chemotherapy with Special Focus on Right-Sided Breast Cancer

Central venous cannulation is a common procedure for administration of chemotherapeutic agents and nutritional support in cancer patients. Mechanical complications most often occur and are closely related to anatomical relationship of great vessels. Use of surface anatomical landmarks along with ultrasound (USG) minimizes these complications. We describe a different safe and easy to replicate method of chemoport insertion using right-sided internal jugular vein (IJV) only in breast cancer patients. The role of real-time ultrasound as a safety enhancer is also reviewed. Chemoport insertion was done in 150 breast cancer patients treated at a tertiary cancer center by use of this modified technique. In our technique, there was a successful cannulation of vein with convenient placement of catheter in all the cases. It is particularly more useful for right-sided breast cancer patients. This technique is safe and easy to replicate method of chemoport placement by using right-sided internal jugular vein.

Effect of radiotherapy on coronary arteries and heart in breast-conserving surgery: a dosimetric analysis.

BackgroundThere are certain risks of radiotherapy (RT), especially patients with left-sided breast cancer have a higher tendency to develop cardiac complications than the right-sided cancers. This study aims to perform a dosi-metric analysis the effect of RT on coronary arteries and heart in breast-conserving surgery.Patients and methodsA total of 40 patients with early stage right and left-sided breast carcinomas (T1/T2 + N0) were randomly selected. RT was delivered to the entire breast, and tumor beds were boosted in these patients using tangential fields with computed tomography based planning. The doses for Left anterior descending coronary artery (LAD), left circumflex coronary artery (LCx), right ventricle (RV), left ventricle (LV), and heart were recorded and median values compared between groups.ResultsThe highest mean of radiation dose in patients with left-sided breast cancer was to LAD 2402.48 ± 838.39 cGy, while the highest mean dose in right-sided breast cancer patients was to RV 130.18 ± 24.92. The highest maximum dose of radiotherapy was applied to heart at left-sided breast cancer patients as well as at right-sides prients. The mean V5 of the LV was 18.68% (6.89–31.69), mean V25 of the LV was 5.22% (0.45–16.54), mean V5 in bilateral ventricles was 23.73% (2.56–26.89), and mean V25 in bilateral ventricles 6.78% (0.63–13.63).ConclusionsEspecially in left-sided breast cancer, the most direct and best strategy to reduce and protect radiation-induced cardiac injury is to balance dose constraints between several high-dose regions of cardiac substructures and the mean heart dose.

Dosimetric Comparison of Deep Inspiration Breath-Hold versus Free Breathing for Right-Sided Breast Cancer with Comprehensive Nodal Radiation

Patients undergoing radiation for breast cancer are at risk of long-term cardiac morbidity and radiation-related coronary artery disease, which is correlated with dose to the heart. Deep inspiration breath-hold (DIBH) technique reduces dose to organs at risk for patients undergoing left breast radiation. The role of DIBH in reducing dose to coronaries, heart, and lungs for right-sided breast cancers is less clear. We evaluated whether treatment planning using DIBH produces significant reduction in right coronary artery (RCA), heart, and lung dose as compared to free breathing (FB) for patients receiving radiation to the breast and regional lymph nodes lymph nodes for right-sided breast cancer. We compared 8 consecutive right-sided breast cancer patients planned with modified wide tangent plans to cover the breast, levels I-III of the axilla, and supraclavicular and internal mammary lymph nodes on paired DIBH and FB CT scans. Lymph nodes were contoured according to the RTOG atlas. RCA was contoured according to the RADCOMP breast atlas available on the RTOG website. All patients were planned to receive 50 Gy in 25 fractions. We compared dose-volume data for DIBH versus FB for RCA, heart, right lung, and total lung. Plan metrics were compared using Wilcoxon signed-rank testing on SPSS. DIBH significantly decreased RCA mean dose, heart maximum point dose, mean heart dose, and heart V5 (Table 1). The difference in maximum point dose and V5 for RCA approached statistical significance (p=0.063 and 0.068, respectively). Mean lung dose for the right lung and total lung were significantly improved with DIBH, as were V20 for the right lung and total lung (Table 1). DIBH resulted in a significantly decreased RCA mean dose as well as a decrease in multiple cardiac and lung dose metrics. DIBH should be considered for right-sided breast cancer patients undergoing radiation to the breast and regional lymph nodes via partial wide tangents.Abstract TU_11_3432: Table 1Organ at risk dose-volume comparison between FB versus DIBHFB MeanBH Meanp-valueRCA D(0.03cc) (cGy)1199333.063RCA D(mean) (cGy)251140.025RCA V5(%)6.80.068Heart D(0.03cc) (cGy)1710552.036Heart D(mean) (cGy)9356.012Heart V5 (%)20.027Right Lung D(mean) (cGy)15241202.036Total Lung D(mean) (cGy)886678.036Right Lung V20 (%)3124.025Total Lung V20 (%)1813.025 Open table in a new tab