Deep Inspiration Breath Hold Technique Research Articles

Minimizing normal tissue low dose bath for left breast Volumetric Modulated Arc Therapy (VMAT) using jaw offset.

With proper beam setup and optimization constraints in the treatment planning system, volumetric modulated arc therapy (VMAT) can improve target dose coverage and conformity while reducing doses to adjacent structures for whole breast radiation therapy. However, the low-dose bath effect on critical structures, especially the heart and the ipsilateral lung, remains a concern. In this study, we present a VMAT technique with the jaw offset VMAT (JO-VMAT) to reduce the leakage and scatter doses to critical structures for whole breast radiation therapy. The data of 10 left breast cancer patients were retrospectively used for this study. CT images were acquired on a CT scanner (GE, Discovery) with the deep-inspiration breath hold (DIBH) technique. The planning target volumes (PTVs) and the normal structures (the lungs, the heart, and the contralateral breast) were contoured on the DIBH scan. A 3D field-in-field plan (3D-FiF), a tangential VMAT (tVMAT) plan, and a JO-VMAT plan were created with the Eclipse treatment planning system. An arc treatment field with the x-jaw closed across the central axis creates a donut-shaped high-dose distribution and a cylinder-shaped low-dose volume along the central axis of gantry rotation. Applying this setup with proper multi-leaf collimator (MLC) modulation, the optimized plan potentially can provide sufficient target coverage and reduce unnecessary irradiation to critical structures. The JO-VMAT plans involve 5-6 tangential arcs (3 clockwise arcs and 2-3 counterclockwise arcs) with jaw offsets. The plans were optimized with objective functions specified to achieve PTV dose coverage and homogeneity; For organs at risk (OARs), objective functions were specified individually for each patient to accomplish the best achievable treatment plan. For tVMAT plans, optimization constraints were kept the same except that the jaw offset was removed from the initial beam setup. The dose volume histogram (DVH) parameters were generated for dosimetric evaluation of PTV and OARs. The D95% to the PTV was greater than the prescription dose of 42.56Gy for all the plans. With both VMAT techniques, the PTV conformity index (CI) was statistically improved from 0.62 (3D-FiF) to 0.83 for tVMAT and 0.84 for JO-VMAT plans. The difference in the homogeneity index (HI) was not significant. The Dmax to the heart was reduced from 12.15Gy for 3D-FiF to 8.26Gy for tVMAT and 7.20Gy for JO-VMAT plans. However, a low-dose bath effect was observed with tVMAT plans to all the critical structures including the lungs, the heart, and the contralateral breast. With JO-VMAT, the V5Gy and V2Gy of the heart were reduced by 32.7% and 15.4% compared to 3D-FiF plans. Significantly, the ipsilateral lung showed a reduction in mean dose (4.65-3.44Gy) and low dose parameters (23.4% reduction for V5Gy and 10.7% reduction for V2Gy) for JO-VMAT plans compared to the 3D-FiF plans. The V2Gy dose to the contralateral lung and breast was minimal with JO-VMAT techniques. A JO-VMAT technique was evaluated in this study and compared with 3D-FiF and tVMAT techniques. Our results showed that the JO-VMAT technique can achieve clinically comparable coverage and homogeneity and significantly improve dose conformity within PTV. Additionally, JO-VMAT eliminated the low-dose bath effect at all OARs evaluation metrics including the ipsilateral/contralateral lung, the heart, and the contralateral breast compared to 3D-FiF and tVMAT. This technique is feasible for the whole breast radiation therapy of left breast cancers.

A Prospective Study on the Use of Deep Inspiration Breath-Hold Technique in External Beam Radiotherapy for Breast Cancer

Background Breast cancer is the most common cancer and the leading cause of death in women. The deep inspiration breath-hold (DIBH) technique helps reduce the dose received by the heart and lungs in breast cancers during adjuvant radiotherapy (RT). We present the dosimetry of heart and lungs with DIBH technique, reproducibility, and ease of execution. Materials and Methods This is a prospective study among breast cancer patients planned for adjuvant RT following either breast conservation or mastectomy. Patients received adjuvant RT to a dose of 42.5 Gy/16 Fr to the chest wall/whole breast followed by a boost of 10 Gy/5 Fr for breast conservation surgery patients with either three-dimensional conformal RT or volumetric modulated arc therapy technique. The dosimetric parameters such as lung mean dose, heart mean dose, and V25 Gy were compared between DIBH and free-breathing (FB) scans. Data were analyzed using SPSS software, and p-value <0.05 was considered statistically significant. Results The study was conducted from September 2018 to August 2020, and 32 patients were included. The compliance to the DIBH technique was good. The dose received by ipsilateral lung V20 (17 vs. 25%) and mean dose (9 vs. 12 Gy) were significantly lower in DIBH compared with FB (p < 0.001). The V5 (31 vs. 15%), V25 (9 vs. 2%), and mean dose (7 vs. 3.3 Gy) to the heart were much higher in FB compared with DIBH (p < 0.001). Conclusion DIBH-based RT treatment delivery for breast cancer patients requiring adjuvant RT showed good compliance and offers a significant reduction in radiation dose to the heart and lung.

Dose delivery error from respiratory motion in free breathing left breast irradiation

PurposeMany institutions worldwide currently deliver left breast radiotherapy in free breathing mode, mostly due to the unavailability of a Deep Inspiration Breath Hold technique (DIBH). This study aims at quantifying the error in dose delivery (compared to treatment plan) due to respiratory motion in free breathing irradiation of left breast or chest wall. Since subfields often consist in small, fine-tuned, highly targeted fields, slight intrafractional target motion may compromise their subtle benefit. Thus we analyzed the respiratory motion effect on target dose coverage, dose homogeneity and left lung dose. MethodsTreatment plans for twenty left breast or chest wall cancer patients previously treated at our center were retrieved and retrospectively planned with the introduction of an appropriate shift in isocenter location to simulate free breathing target motion. ResultsNo clinically significant dosimetric changes were found in all twenty cases when breathing motion was accounted for. Changes in target dose coverage (V95%), in target maximum dose (D2%) and in V20Gy lung dose were respectively less than 1.5%, 0.3% and 2.6%. ConclusionThe findings suggest that breast irradiation in free breathing mode does not undermine the dosimetric merits of the field-in-field technique and does not produce clinically significant dosimetric differences in dose delivery for target and lung compared to plan.

Spot-scanning proton therapy for early breast cancer in free breathing versus deep inspiration breath-hold.

Proton therapy for breast cancer is usually given in free breathing (FB). With the use of deep inspiration breath-hold (DIBH) technique, the location of the heart is displaced inferiorly, away from the internal mammary nodes and, thus, the dose to the heart can potentially be reduced. The aim of this study was to explore the potential benefit of proton therapy in DIBH compared to FB for highly selected patients to reduce exposure of the heart and other organs at risk. We aimed at creating proton plans with delivery times feasible with treatment in DIBH. Sixteen patients with left-sided breast cancer receiving loco-regional proton therapy were included. The FB and DIBH plans were created for each patient using spot-scanning proton therapy with 2-3 fields, robust and single field optimization. For the DIBH plans, minimum monitor unit per spot and spot spacing were increased to reduce treatment delivery time. All plans complied with target coverage constraints. The median mean heart dose was statistically significant reduced from 1.1 to 0.6 Gy relative biological effectiveness (RBE) by applying DIBH. No statistical significant difference was seen for mean dose and V17Gy RBE to the ipsilateral lung. The median treatment delivery time for the DIBH plans was reduced by 27% compared to the FB plans without compromising the plan quality. The median absolute reduction in dose to the heart was limited. Proton treatment in DIBH may only be relevant for a subset of these patients with the largest reduction in heart exposure.

Dosimetric Impact of Voluntary Deep Inspiration Breath Hold (DIBH) in Mediastinal Hodgkin Lymphomas: A Comparative Evaluation of Three Different Intensity Modulated Radiation Therapy (IMRT) Delivery Methods Using Voluntary DIBH and Free Breathing Techniques.

Hodgkin lymphomas are radiosensitive and curable tumors that often involve the mediastinum. However, the application of radiation therapy to the mediastinum is associated with late effects including cardiac and pulmonary toxicities and secondary cancers. The adoption of conformal IMRT and deep inspiration breath- hold (DIBH) can reduce the dose to healthy normal tissues (lungs, heart and breast). We compared the dosimetry of organs at risk (OARs) using different IMRT techniques for two breathing conditions, i.e., deep inspiration breath hold (DIBH) and free breathing. Twenty-three patients with early-stage mediastinal Hodgkin lymphomas were accrued in the prospective study. The patients were given treatment plans which utilized full arc volumetric modulated arc therapy (F-VMAT), Butterfly VMAT (B-VMAT), and fixed field IMRT (FF-IMRT) techniques for both DIBH and free breathing methods, respectively. All the plans were optimized to deliver 95% of the prescription dose which was 25.2 Gy to 95% of the PTV volume. The mean dose and standard error of the mean for each OAR, conformity index (CI), and homogeneity index (HI) for the target using the three planning techniques were calculated and compared using Student's t-test for parametric data and Wilcoxon signed-rank test for non-parametric data. The HI and CI of the target was not compromised using the DIBH technique for mediastinal lymphomas. The mean values of CI and HI for both DIBH and FB were comparable. The mean heart doses were reduced by 2.1 Gy, 2.54 Gy, and 2.38 Gy in DIBH compared to FB for the F-VMAT, B-VMAT, and IMRT techniques, respectively. There was a significant reduction in V5Gy, V10Gy, and V15Gy to the heart (p < 0.005) with DIBH. DIBH reduced the mean dose to the total lung by 1.19 Gy, 1.47 Gy, and 1.3 Gy, respectively. Among the 14 female patients, there was a reduction in the mean right breast dose with DIBH compared to FB (4.47 Gy vs. 3.63 Gy, p = 0.004). DIBH results in lower heart, lung, and breast doses than free breathing in mediastinal Hodgkin Lymphoma. Among the different IMRT techniques, FF-IMRT, B-VMAT, and F-VMAT showed similar PTV coverage, with similar conformity and homogeneity indices. However, the time taken for FF-IMRT was much longer than for the F-VMAT and B-VMAT techniques for both breathing methods. B-VMAT and F-VMAT emerged as the optimal planning techniques able to achieve the best target coverage and lower doses to the OARs, with less time required to deliver the prescribed dose.

Dosimetric advantages for cardiac substructures in radiotherapy of esophageal cancer in deep-inspiration breath hold.

Radiotherapy is one of the main treatment options for patients with esophageal cancer; however, it has been linked with an increased risk of cardiac toxicities. In the current study, we evaluated the effect of planning the radiation in deep-inspiration breath hold (DIBH) on the dose sparing of cardiac substructures and lung. In this study, we analyzed 30radiation therapy plans from 15patients diagnosed with esophageal cancer planned for neoadjuvant radiotherapy. Radiation plans were generated for 41.4 Gy and delivered in 1.8 Gy per fraction for free-breathing (FB) and DIBH techniques. We then conducted acomparative dosimetric analysis, evaluating target volume coverage, the impact on cardiac substructures, and lung doses across the two planning techniques for each patient. There was no significant disparity in target volume dose coverage between DIBH and FB plans. However, the Dmean, D2%, and V30% of the heart experienced substantial reductions in DIBH relative to FB, with values of 6.21 versus 7.02 Gy (p = 0.011), 35.28 versus 35.84 Gy (p = 0.047), and 5% versus 5.8% (p = 0.048), respectively. The Dmean of the left ventricle was notably lower in DIBH compared to FB (4.27 vs. 5.12 Gy, p = 0.0018), accompanied by significant improvements in V10. Additionally, the Dmean and D2% of the left coronary artery, as well as the D2% of the right coronary artery, were significantly lower in DIBH. The dosimetric impact of DIBH on cardiac substructures proved more advantageous for middle esophageal (ME) than distal esophageal (DE) tumors. Radiotherapy in DIBH could provide amethod to reduce the radiation dose to the left ventricle and coronaries, which could reduce the cardiac toxicity of the modality.

Deep inspiration breath hold real-time tumor-tracking radiation therapy (DBRT) as a novel stereotactic body radiation therapy approach for lung tumors

Radiotherapy with deep inspiration breath hold (DIBH) reduces doses to the lungs and organs at risk. The stability of breath holding and reproducibility of tumor location are higher during expiration than during inspiration; therefore, we developed an irradiation method combining DIBH and real-time tumor-tracking radiotherapy (RTRT) (DBRT). Nine patients were enrolled in this study. Fiducial markers were placed near tumors using bronchoscopy. Treatment planning computed tomography (CT) was performed thrice during DIBH, assisted by spirometer-based device. Each CT scan was fused using fiducial markers. Gross tumor volume (GTV) was contoured for each dataset and summed to create GTVsum; adding a 5-mm margin around GTVsum generated the planning target volume. The prescribed dose was mainly 42 Gy in four fractions. The treatment plan was created using DIBH CT (DBRT-plan), with a similar treatment plan created for expiratory CT for cases for which DBRT could not be performed (conv-plan). Vx defined as the volume of the lung received x Gy, and the mean lung dose, V20, V10, and V5 were evaluated. DBRT was completed in all patients. Mean dose, V20, and V10 were significantly lower in the DBRT-plan than in the conv-plan (all p = 0.003). Mean rates of decrease for mean dose, V20, and V10 were 14.0%, 27.6%, and 19.1%, respectively. No significant difference was observed in V5. We developed DBRT, a stereotactic body radiation therapy performed with the DIBH technique; it combines a spirometer-based breath-hold support system with an RTRT system. All patients who underwent DBRT completed the procedure without any technical or mechanical complications. This is a promising methodology that may significantly reduce lung doses.

Chest Wall to Heart Distance Reproducibility in Postoperative Deep Inspiration Breath-Hold Radiotherapy for Left-Sided Breast Cancer Using an Anzai Laser Sensor With Visual Feedback.

Background Left-sided breast cancer radiotherapy may increase the risk of cardiovascular death due to possible heart irradiation. Thereproducibility of the chest wall to heart distance in deep inspiration breath-hold (DIBH) was studied using a laser sensor with visual feedback. Methodology A total of 10 consecutive postoperative left-sided breast cancer cases receiving DIBH radiotherapy between December 2022 and September 2023 were retrospectively investigated. The prescribed dose was 50 Gy in 25 fractions. An Anzai respiratory gating system, AZ-733VI (Anzai, Tokyo, Japan), was employed that has a laser displacement sensor and a visual feedback device. An Elekta linac with a cone-beam CT unit, Axesse (Elekta AB, Stockholm, Sweden), was used in this study. The interfractional changes in the chest wall to heart distance among 25 fractions were analyzed for each of the 10 patients in each coordinate axis. In addition, the median with the 95% confidence interval (CI) and interquartile range (IQR) for all 250 fractions were calculated in each axis to assess the reproducibility of our DIBH technique. Results The medians of the interfractional changes in the chest wall to heart distance in each of the 10 patients ranged from -2 mm to 3 mm, -1 mm to 3 mm, and -2 mm to 1 mm in the lateral (X), superior-inferior (Y), and anterior-posterior (Z) directions, respectively. For all 10 cases, the medians were 1 mm (95% CI = 0.72 to 1.28 mm) in X, 1 mm (95% CI = 0.76 to 1.24 mm) in Y, and 0 mm (95% CI = -0.20 to 0.20 mm) in Z directions, whereas the IQRs were 4 mm in X, 2 mm in Y and 2 mm in Z directions. The measured IQRs were two to three times smaller than those shown in a previous report without visual feedback, suggesting a clinical advantage of the visual feedback in DIBH for left-sided breast cancer radiotherapy. The DIBH solution shown in this study required approximately 10 minutes from room-in to room-out, thereby not reducing the daily number of patients. Conclusions Our DIBH approach with visual feedback achieved better distance reproducibility between the chest wall and heart by a factor of two to three in terms of IQR compared to the previously reported data without visual feedback. Patient throughput was also favorable. To our knowledge, this is the first report demonstrating the chest wall to heart distance reproducibility in DIBH with visual feedback.

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).

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. 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. 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 4mm in the lateral, longitudinal, and vertical directions if based on SGRT alone. The intrafractional error contributed ≤1mm to the calculated setup margins. 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.

Correlation between maximum heart distance and thoracic diameter changes and diaphragmatic descent in left-sided breast cancer patients during deep inspiration breath-hold (DIBH).

Cardioprotection is valued in radiotherapy for patients with left-sided breast cancer. Deep inspiration breath-hold (DIBH) technique can achieve cardioprotection well. However, during DIBH, the extent to which the heart enters the radiation field is affected by the movement of the thorax and diaphragm. The aim of this study was to analyze the correlation between the maximum distance of the heart entering the field (maximum heart distance, MHD) and thoracic diameter changes and diaphragmatic descent in left-sided breast cancer patients during DIBH. Ninety-eight patients with left-sided breast cancer were included in this retrospective study. They performed simulation in Sentinel-guided DIBH, and two sets of CT images were collected under both free breathing (FB) and DIBH, and diaphragm positions, anteroposterior thoracic diameter (ATD), transverse thoracic diameter (TTD), gating window level (GWL), and MHD were measured, and the change (Δ) of each parameter in DIBH relative to that in FB were calculated. Pearson or Spearman test were used to analyze the correlation between ΔMHD and the changes in other parameters. For all patients with DIBH, the average of ΔMHD was -8.3 mm, and the average of ΔATD and ΔTTD were 11.0 and 8.6 mm, and the median of both left diaphragmatic descent (LDD) and right diaphragmatic descent (RDD) were 35.0 mm, and the median of GWL was 11.1 mm. The correlation coefficients between MHD decrease (ΔMHD) and LDD, RDD, and ΔTTD were -0.430 (p = 0.000), -0.592 (p = 0.000) and 0.208 (p = 0.040), respectively, but not significantly correlated with ΔATD or GWL. The MHD decrease showed a moderate correlation with diaphragmatic descent In Sentinel-guided DIBH for patients with left-sided breast cancer, while there was a weak or no correlation with thoracic diameter changes or GWL. Abdominal breathing can lower diaphragm more and may be more beneficial to the heart stay away from tangential field.

Active Breathing Coordinator reduces radiation dose to the stomach in patients with left breast cancer

Background/Purpose Gastric dose parameters comparison for deep inspiration breath-hold (DIBH) or free breathing (FB) mode during radiotherapy (RT) for left-sided breast cancer patients (LSBCPs) has not been investigated before. This study aimed to analyze the impact of Active Breath Coordinator (ABC)-DIBH technique on the dose received by the stomach during RT for LSBCPs and to provide organ-specific dosimetric parameters. Materials and methods The study included 73 LSBCPs. The dosimetric parameters of the stomach were compared between FB and DIBH mode. The correlation between the stomach volume and dosimetric parameters was analyzed. Results Compared to FB mode, statistically significant reductions were observed in gastric dose parameters in ABC-DIBH mode, including Dmax (46.60 vs 17.25, p < 0.001), D1cc (38.42 vs 9.60, p < 0.001), Dmean (4.10 vs 0.80, p < 0.001), V40Gy (0.50 vs 0.00, p < 0.001), V30Gy (6.30 vs 0.00, p < 0.001), V20Gy (20.80 vs 0.00, p < 0.001), V10Gy (51.10 vs 0.77, p < 0.001), and V5Gy (93.20 vs 9.60, p < 0.001). ABC-DIBH increased the distance between the stomach and the breast PTV when compared to FB, from 1.3 cm to 2.8 cm (p < 0.001). Physiologic decrease in stomach volume was not found from FB to ABC-DIBH (415.54 cm3 vs 411.61 cm3, p = 0.260). The stomach volume showed a positive correlation with V40Gy (r2 = 0.289; p < 0.05), V30Gy (r2 = 0.287; p < 0.05), V20Gy (r2 = 0.343; p < 0.05), V10Gy (r2 = 0.039; p < 0.001), V5Gy (r2 = 0.439; p < 0.001), Dmax (r2 = 0.269; p < 0.05) and D1cc (r2 = 0.278; p < 0.05) in FB mode. While in ABC-DIBH mode, most stomach dosimetric parameters were not correlated with gastric volume. Conclusions The implementation of ABC-DIBH in LSBCPs radiotherapy resulted in lower irradiation of the stomach. Larger stomach volume was associated with statistically significantly higher dose irradiation in FB mode. To reduce radiotherapy related side effects in FB mode, patients should be fast for at least 2 hours before the CT simulation and treatment.

Investigation of Intra-fraction Stability and Inter-fraction Consistency of Active Breathing Coordinator (ABC)-Based Deep Inspiration Breath Holds in Left-Sided Breast Cancer.

Background Deep inspiration breath-hold (DIBH) has been established as a standard technique to reduce cardiac dose. The part of the heart exposed to radiation can be significantly decreased using the DIBH technique during tangential left-sided breast cancer (LSBC) irradiation. Aim The objective of this study was to investigate the intra-fraction breath-hold stability and inter-fraction consistency of patient breath-hold against the threshold as a function of air volumes in the setting of active breathing coordinator (ABC)-based DIBH (ABC-DIBH) treatment to LSBC. Methods A total of 34 patients treated with external beam radiation therapy (EBRT) to the left breast using the ABC-DIBH device were included. The frequency of breath-holds perfraction and the entire course of treatment along with the total treatment time was evaluated for all patients.A prescription dose of either 200 cGy (conventional) or 267 cGy (hypofractionation) was administered during 649 fractions, resulting in a total of 4,601 breath-hold measurements being evaluated. The amplitude of deviation in terms of air volumes between the baseline threshold and the patient-specific measurement (during each breath-hold) per fraction was used to define the DIBH stability. Likewise, the consistency of the breathing amplitudes was used to define the compliance of patient breath-holds throughout the entire treatment period. Positional accuracy was evaluated using orthogonal (portal) images. Results The average number of breath-holds measured over the entire course of treatment for each patient was 144 inspirations (58-351). Similarly, the average number of breath-holds for each fraction during the course of treatment was 11 inspirations (7-21), which included setup imaging and treatment. The total number of breath-holds reduced significantly (p-value < 0.05) with hypofractionation (104 inspirations; range 58-170) as compared to conventional fractionation (145 inspirations; 58-351). The average breath-hold threshold in terms of air volume was 1.41 L(0.6-2.1 L) for all patients. The total treatment time reduced significantly after the third fraction (p-value < 0.05).The average deviation between the measured and baseline threshold breath-holds during the course of treatment was 0.5 L/sec (0.12-1.32 L/sec). The consistency of the breathing amplitudes were maintained within±0.05 Lduring the entire treatment for all patients. The average translational shifts measured during setup were 0.28 cm ± 0.3 cm, 0.38 cm ± 0.4 cm, and 0.21 cm ± 0.3 cm in the lateral, longitudinal, and vertical directions, respectively. Conclusion The study has demonstrated the variations in intra-fraction breath-hold stability and inter-fraction breath-hold consistency in terms of air volumes for patients who were treated for LSBC. The frequency of breath-holds was observed to be higher with increased total treatment time for the first few fractions and reduced over the course of treatment.

Evaluation of the accuracy of heart dose prediction by machine learning for selecting patients not requiring deep inspiration breath‑hold radiotherapy after breast cancer surgery.

Increased heart dose during postoperative radiotherapy (RT) for left-sided breast cancer (BC) can cause cardiac injury, which can decrease patient survival. The deep inspiration breath-hold technique (DIBH) is becoming increasingly common for reducing the mean heart dose (MHD) in patients with left-sided BC. However, treatment planning and DIBH for RT are laborious, time-consuming and costly for patients and RT staff. In addition, the proportion of patients with left BC with low MHD is considerably higher among Asian women, mainly due to their smaller breast volume compared with that in Western countries. The present study aimed to determine the optimal machine learning (ML) model for predicting the MHD after RT to pre-select patients with low MHD who will not require DIBH prior to RT planning. In total, 562 patients with BC who received postoperative RT were randomly divided into the trainval (n=449) and external (n=113) test datasets for ML using Python (version 3.8). Imbalanced data were corrected using synthetic minority oversampling with Gaussian noise. Specifically, right-left, tumor site, chest wall thickness, irradiation method, body mass index and separation were the six explanatory variables used for ML, with four supervised ML algorithms used. Using the optimal value of hyperparameter tuning with root mean squared error (RMSE) as an indicator for the internal test data, the model yielding the best F2 score evaluation was selected for final validation using the external test data. The predictive ability of MHD for true MHD after RT was the highest among all algorithms for the deep neural network, with a RMSE of 77.4, F2 score of 0.80 and area under the curve-receiver operating characteristic of 0.88, for a cut-off value of 300 cGy. The present study suggested that ML can be used to pre-select female Asian patients with low MHD who do not require DIBH for the postoperative RT of BC.

The Impact of Deep Inspiration Breath Hold (DIBH) Implementation on the Hybrid Technique in Left-Sided Whole Breast Irradiation: A Dosimetric Characteristic Study of 3D-CRT Hybrid VMAT in DIBH and Free Breathing Conditions, and VMAT in Free Breathing Conditions.

To investigate the impact of DIBH for heart sparing effect on left sided breast postoperative whole breast irradiation by comparing the dosimetric characteristics of 3D-CRT hybrid VMAT and pure VMAT treatment planning under DIBH condition. The primary CT data sets from previously treated left sided early breast cancer were used for pure volumetric arc therapy (VMAT) technique re-planning for the dosimetric characteristics comparison. A treatment plan of 3D-CRT hybrid VMAT technique was re-planned on the free breath (FB) condition for the investigation of the dosimetric characteristics comparison on DIBH condition. The prescribed dose for all the treatment plans was 42.5Gy in 16 fractions. All plans were optimized to cover 100% of the PTV by 95% of prescribed dose. The dosimetric differences among the 3 treatment plans for the 20 patients were analyzed using Wilcoxon signed-rank test, with p value<0.05 considered statistically significant. 3D-CRT hybrid VMAT using DIBH technique yielded the best results on the conformity index (CI) and homogeneity index (HI). By comparing this 3D-CRT hybrid VMAT technique using FB and DIBH technique, the mean heart dose (MHD) was reduced from 5.38Gy to 1.65Gy, respectively (p =0.001) and the left anterior descending coronary artery (LAD)0.03cc dose was reduced from 27.87Gy to 9.41Gy, respectively (p =0.001). 3D-CRT hybrid VMAT using DIBH technique significantly reduced the V5, V20 and D mean of the ipsilateral lung and D mean of the contralateral lung. The D5 of right breast was significantly reduced by 3D-CRT hybrid VMAT compared with VMAT using DIBH technique. The incorporation of DIBH into 3D-CRT hybrid VMAT technique provides the best benefits for the heart and the OAR with respect to the radiation dose-sparing effect without compromising the target conformity and homogeneity in the treatment planning.

Evaluation of Daily Patient Position Accuracy and Calculation of Setup Errors with Skin Markers and Surface-Guided Radiotherapy (SGRT) in Breast Cancer

This study aims to compare the inter-fractional patient positioning errors between the use of skin markers and SGRT in patients receiving breast radiotherapy. It also includes calculating the inter- and intra-fractional PTV margins required for free breathing (FB) and deep inspiration breath-hold (DIBH) techniques due to setup uncertainties. The treatment data of a total of 2209 fractions from 80 patients who received whole breast or chest wall radiotherapy at an institution between March 2021 and December 2022 were retrospectively analyzed. In the first group of patients, the skin markers placed in the Computed Tomography (CT) scan with the FB technique were aligned and positioned with the room lasers in the Elekta Versa HD, and plan-specific shifts were made. The optical surface scanning procedure was applied to the second group of patients with the Sentinel™ system for FB or DIBH techniques in simulation. Patients were positioned for treatment by matching reference surface images with real-time images from the Catalyst™ HD surface imaging system. Positions of all patients were verified with kilovoltage or cone-beam CT imaging systems, and 3D shift vectors were recorded daily. To compare both setup methods, PTV margins including mean positioning shifts (MPS), the vector length of the shifts and setup errors were calculated from van Herk's formulas. The MPS of all patients using skin markers were 0.20±0.85 cm, 0.32±1.55 cm, and 0.18±0.44 cm in the vertical, longitudinal and lateral directions, respectively. Then, these values given above were found to be 0.12±0.15 cm, 0.06±0.17 cm, 0.07±0.23 cm for FB using Catalyst™ HD, and 0.34±0.30 cm, 0.29±0.26 cm, 0.23±0.30 cm for DIBH. In different setup techniques, no statistically significant difference was found between the 3D shift vectors in any direction with Wilcoxon signed-rank test (p>0.05). The mean standard deviation values in all directions were calculated as 1.22 cm and 0.61 cm, respectively, in patients using skin markers and SGRT. This study indicates a significant difference between the positioning shifts of patients positioned with skin markers and SGRT. The surface imaging system is an advantageous non-invasive method that increases setup accuracy and reproducibility in breast radiotherapy.

The Effect of Deep Inspiration Breath-Hold Technique on Right Coronary Artery, Heart, and Liver Doses in Right Breast Cancer Radiotherapy

The deep inspiration breath-hold (DIBH) approach has been thoroughly researched with the aim of reducing radiation exposures to normal tissues in breast cancer patients. Although heart and lung toxicity are widely addressed in many literature, radiation-associated liver toxicity and dose constraints for the right coronary artery (RCA) are not well studied in relation to breast radiotherapy. Additionally, very few studies have investigated the relationship between doses to cardiac substructures. This study aimed to determine the effect of the DIBH technique on the right coronary artery (RCA) region, cardiac substructures, and liver dose in right breast cancer irradiation. Between January 2022 and December 2022, thirty-five right breast cancer patients who previously received breast-surgery underwent computed tomography (CT) simulation with both free-breathing (FB) and DIBH techniques. Patients were contoured by a radiation oncologist on the scans using the Treatment Planning System. For cardiac substructures, reference atlas contours were used for accurate delineation and to reduce inter-observer variation. Each patient underwent two treatment plans for both the DIBH and FB datasets. The plan comprised the FB and DIBH techniques, and the doses to the cardiac substructures, ipsilateral lung, RCA region, and liver were compared using a two-tailed paired t-test. Radiotherapy was delivered with a Linac with the prescription dose of 50 Gy in 25 fractions. For both FB and DIBH irradiation groups, the mean radiation doses to the ipsilateral lung, heart, and RCA region in patients with FB and DIBH techniques were; 14.67 Gy, 2.33 Gy, 4.88 Gy and 12.05 Gy, 1.34 Gy and 3.29 Gy respectively. The mean radiation doses to the cardiac substructures; for the left ventricle, right ventricle, left atrium, and right atrium for the FB were 1.08 Gy, 1.79 Gy, 4.11 Gy, and for DIBH, 0.49 Gy, 1.49 Gy, 0.95 Gy, and 2.61 Gy, respectively. For the DIBH group, the liver maximum dose (p<0.01), right lung mean dose (p = 0.001), heart maximum dose (p = 0.009), RCA mean dose (p = 0.020), RCA maximum dose (p = 0.008), RCA V5 dose (p = 0.035), right atrium maximum dose (p = 0.009) and right ventricle mean dose (p = 0.040) were significantly lower than in patients treated in the non-gated group. DIBH resulted in considerable displacement of the liver away from the high-dose target region, such that the volume of liver in the high-dose region was reduced. Additionally, the use of the DIBH technique in right breast cancer irradiation effectively reduces the radiation doses to the cardiac substructures, such as the left ventricle, right ventricle, left atrium, right atrium, RCA region, and lungs. DIBH could lead to substantial sparing of these structures with the right breast cancer radiotherapy. Future prospective studies are required to determine whether improvements to dose-distribution will translate into improved toxicity outcomes.

Early Cardiotoxicity in Patients Receiving Hypofractionated Radiotherapy after Breast Conserving Surgery: Analysis of a Prospective Study

To evaluate the early cardiotoxicity of hypofractionated radiotherapy (HFRT) in patients with left-sided breast cancer after breast-conserving surgery, and to investigate the correlation between cardiotoxicity and cardiac dose. A total of 103 women from 2017 to 2018 who received left-sided whole-breast with or without regional nodal irradiation either using deep inspiration breath-hold (DIBH) or free-breathing (FB) technique were prospectively enrolled. N-terminal pro-B-type natriuretic peptide (NT-proBNP), electrocardiogram, and radionuclide myocardial perfusion imaging were conducted before and after HFRT. Logistic regression analyses were performed to determine the association of cancer treatment, cardiac dose, and cardiovascular risk factors with cardiotoxic effects. The mean dose (Dmean) of the heart, left anterior descending coronary artery (LAD), left ventricular (LV), and right ventricular (RV) in all patients was 403 cGy, 1685 cGy, 627 cGy, and 444 cGy, respectively. In comparison to FB, DIBH significantly reduced cardiac dose (heart Dmean 250 cGy vs. 570 cGy, LAD Dmean 1250 cGy vs. 2170 cGy, LV Dmean 420 cGy vs. 850 cGy, RV Dmean 260 cGy vs. 650 cGy; all p<0.001). With a median follow-up of 49 months (range, 2-65 months), no patients had clinical cardiac abnormalities or cardiac-related symptoms, but 42 (41%) patients had subclinical cardiac events. Among them, 41 were electrocardiogram changes, and one had LV ejection fraction decreased by 10% compared with the baseline level. Twenty-five (60%) recovered during follow-up, of which 17 (40%) experienced subclinical changes only once. The mean value of NT-proBNP did not change significantly before and after HFRT. In univariate analyses, DIBH technique significantly decreased the risk of subclinical cardiac events compared with FB (OR 0.31, 95% CI 0.14-0.71; p = 0.006); however, higher mean doses of heart and LV, anthracycline-based chemotherapy, obesity, and hypertension were associated with increased risk of subclinical cardiac events (all p<0.05). Early subclinical cardiac damage after HFRT in left-sided breast cancer is dose-related, and mostly manageable and reversible without medical intervention.

The Impact of Cardiac Sparing Techniques on Major Cardiac Events for Patients Undergoing Breast Radiotherapy

In radiotherapy, studies with historical estimates have shown a linear relationship between cardiac dose and risk of major cardiac events with no safe dose threshold. This study investigates the relationship between cardiac dose and event rates for patients undergoing breast radiotherapy with modern heart-sparing techniques, where substantially lower cardiac doses are achieved. From 2008 to 2018, all patients undergoing curative whole breast or chest wall radiotherapy at a tertiary care center were included. In this study, the deep-inspiration breath hold (DIBH) technique was implemented in 2013 as the standard of care for left-sided patients. Cardiacdosimetricdata from the clinical treatment plan was extracted and matched to patients from the ongoing, prospectively collected Alberta Provincial Project for Outcome Assessment in Coronary Heart disease (APPROACH) database that experienced a major adverse cardiac event (MACE). MACE was defined as myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure,or clinically indicated coronary revascularization.For all the left- and right-sided patients, the population event rates, the median time to event, and the average (± standard deviation) of the mean heart physical dose is reported. The proportion of left- and right-sided patients experiencing a major cardiac event were tested for independence using a two-sample z-test for proportions. A student's t-test was used to measure significance for mean heart dose. An alpha of 0.05 was used to indicate significance for both tests. A total of 4893 patients received breast radiotherapy with 2429 left-sided, 2429 right-sided, and 35 synchronous bilateral. For all patients, Table 1 describes laterality, treatment characteristics, and prescription. The median (range) age at the time of first radiotherapy treatment was 59 (23-94). Of these patients with contours available, 96 left-sided (3.9%) and 69 right-sided (2.8%) patients experienced a MACE (p = 0.03) with a mean heart dose of 1.4 (±0.7)Gyand 0.5 (±0.2)Gy, in the event cohorts respectively (p < 0.001). The mean time to event was 4.7 (±3.2) years and 4.8 (±3.0) years for left- and right-sided patients, respectively (p = 0.83). For the left-sided cohort treated with DIBH, the mean heart dose is 1.0 (±0.8)Gy. In the era of modern radiotherapy and cardiac-sparing techniques, mean heart dose and corresponding event rates are stillsignificantlyhigher for left-sided patients than right-sided patients. Future work will aim to test whether there is a safe threshold for cardiac dose in the context of these results.

Application of Deep Inspiration Breath Hold Technique in Radiotherapy After Breast- Conserving Surgery for Left Breast Cancer and Its Improvement on Cardiac Dose

Objective: To analyze the application of deep inspiration breath hold technique in radiotherapy after breast-conserving surgery for left breast cancer and the improvement of cardiac dose. Methods: A total of 45 patients with left breast cancer treated in our hospital after breast-conserving surgery were selected, and the selection time was set from January 2020 to August 2022. All patients received radiotherapy. The right breast, heart, and lung volumes, and dose parameters of the heart, lungs, right breast, and left anterior descending coronary artery were compared under free breathing (FB) and deep inspiration breath hold (DIBH) technical modes. Results: The heart volume of the DIBH group was smaller than that of the FB group, and the left and right lung volumes were significantly larger than those of the FB group. In the DIBH group, the heart dose parameters V5, proper lung dose parameters, and left anterior descending coronary artery dose parameters were found lower than that of the FB group, and the differences were statistically significant (P &lt; 0.05). Conclusion: Compared with FB, the DIBH technique can reduce the heart’s size and increase the lung volume when used for radiotherapy after breast-conserving surgery for left breast cancer. It also reduces the dose to the heart, right lung, and left anterior descending coronary artery, thus protecting the heart and lungs.

Dosimetric evaluation of accelerated partial breast irradiation (APBI) using volumetric modulated arc therapy (VMAT) technique

Purpose: Five-fraction radiation therapy treatment regimens for accelerated partial breast irradiation (APBI) using intensity modulated radiotherapy (IMRT) have become increasingly used after several phase three trials demonstrated similar or reduced toxicity compared with whole breast irradiation. Improving the treatment efficiency of this technique could significantly improve delivery accuracy and tolerability, especially for treatment plans utilizing deep inspiration breath hold (DIBH) technique. The aim of this study was to determine the optimal technique for APBI, with a focus on volumetric modulated arc therapy technique (VMAT) and flattening-filter free (FFF) delivery. Methods: Ten APBI cases, five cases each left and right breast, were randomly selected. Each case was contoured following guidelines included in the APBI-IMRT-Florence Trial and planned to use both non-coplanar static-field IMRT with standard flattened-filter (FF) beam and VMAT techniques with both FF and FFF beam. For each VMAT plan, two partial arcs were used with patient-specific start and stop angles. Arc extents emulated opposed tangential fields and were chosen based on target and organ at risk (OAR) locations. Evaluated OARs included the heart, ipsilateral and contralateral lung, and normal breast. All plans were generated using the Eclipse treatment planning system (Version 15.6). A prescription dose of 30Gy delivered in 5 fractions was used for all cases. Plans were compared and evaluated using several dose metrics as well as treatment time. Results: For targets, VMAT exhibited similar coverage (V95%) but higher Dmax compared to IMRT (105% (IMRT) v.s .111% (VMAT), p=0.002. VMAT provided similar OAR avoidance compared to IMRT for the heart (Dmean, V3Gy, V0.5Gy), ipsilateral lung (V10Gy), contralateral lung (V5Gy) and contralateral breast Dmax within 10cGy/2% (p~0.005). VMAT contributed slightly lower dose outside the target in the ipsilateral breast, with an average difference in V15Gy of approximately 8% (37% (IMRT) v.s. 29% (VMAT)). Finally, because IMRT delivery is non-coplanar, and typically requires at least 5 treatment fields, co-planar VMAT reduced the total treatment significantly. VMAT with FF beam energies also used fewer monitor unites compared to IMRT with FF beam energies. The utilization of FFF beam energies for VMAT further improved delivery time compared to IMRT. Overall, VMAT with FFF beam energies reduced treatment time by approximately 20% compared to IMRT with FF beam. Conclusions: Co-planar partial-arc FFF VMAT technique produced equivalent target coverage, improved efficiency, better normal tissue sparing, and shorter delivery time compared to non-coplanar IMRT technique. Shorter delivery time also assists in the reduction of patient motion associated with breath hold. VMAT technique with FFF delivery is a suitable replacement for IMRT in APBI.