Left-sided Breast Cancer Patients Research Articles

Ultrahypofractionated Adjuvant Proton Therapy for Localized Stage Breast Cancer: Early Toxicity Report

<h3>Purpose/Objective(s)</h3> To report early toxicity and dosimetry data in breast cancer patients treated with ultrahypofractionated proton therapy (Ultra-HF-PT). <h3>Materials/Methods</h3> Patients with localized breast cancer (Tis-T2, N0) who required postoperative whole-breast radiotherapy were eligible. The prescribed dose was 26 Gy in 5 daily fractions ± single fraction 5,2 Gy boost. Treatment planning was performed with 1 or 2 anterior fields (0°±40°) using multi-field optimization. Robust optimization was performed on the CTV structure with a 3- mm setup uncertainty and a 3.5% range uncertainty. For 69% of patients with left-sided cancer deep inspiration breath hold technique (DIBH) was used. The target coverage was defined as V_100%>98% (>98% of volume receiving 100% of the prescribed dose). Patients were seen weekly while on treatment, at 1 month after radiation therapy completion, and at 3-month intervals thereafter. Toxicity was scored using CTCAE ver. 5.0. <h3>Results</h3> From July 2020 to November 2021, 63 patients were treated with intensity-modulated proton therapy. Median follow-up was 9 months (2 to 18). During radiotherapy Grade 1 and 2 dermatitis occurred in 45 (71%) and 4 (6%) patients respectively. After the end of treatment Grade 1 or 2 dermatitis occurred in all patients, resolving in 4 weeks. Mean dose to the left anterior descending coronary artery (LAD) was 1,28 Gy (0,12-8,2) for left-sided breast cancer patients. Mean ipsilateral lung dose was 2,66 Gy (0,55-5,8). Compared to free breathing DIBH significantly reduced mean dose to the heart (0,4 to 0,1 Gy, p=0,03) and LAD (2,5 to 1,2 Gy, p=0,03) in patients with left-sided cancer. <h3>Conclusion</h3> Limited data exists demonstrating the clinical benefit of proton radiotherapy (PRT) in breast cancer. This study is the first report of clinical data for Ultra-HF-PT in patients with localized breast cancer. Treatment was well tolerated, with acceptable rates of skin toxicity, providing low dose to normal tissue without compromising target coverage. Dose reduction to organs at risk might translate into the reduction of late toxicities.

Assessing Acute Cardiac Inflammation after Left-Sided Breast Cancer Radiotherapy with Hybrid PET/MRI (RICT-BREAST)

<h3>Purpose/Objective(s)</h3> The goal of this study is to investigate the utility of hybrid ¹⁸FDG PET/MRI and serial blood work to detect early inflammatory response and cardiac functionality changes at one-month and one-year post radiation therapy (RT) in patients with left-sided breast cancer. <h3>Materials/Methods</h3> Fifteen left-sided breast cancer patients are currently enrolled in the RICT-BREAST study (NCT03748030). Serial imaging with hybrid ¹⁸FDG PET/MRI and blood work was obtained at baseline (before RT), at one-month post RT, and at one-year post RT. The hybrid ¹⁸FDG PET/MR imaging protocol consisted of a sixty-minute list-mode ¹⁸FDG PET scan with prior glucose suppression. Myocardial inflammation was quantified by calculating the change of mean ¹⁸FDG standard uptake (meanSUV_bw) at 40-60 minutes post injection and was grouped based on the supplied artery (left anterior descending (LAD), left circumflex (LC) or right coronary artery (RCA)). MRI assessments, including left ventricle (LV) functional and extracellular volume matrices (ECV), were extracted from T1 (pre and during-constant infusion of gadolinium) and cine images, respectively, and acquired simultaneously during PET acquisition. Cardiac disease and inflammation biomarker measurements of high-sensitivity troponin T (hs-TnT), C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR) were compared at each timepoint. <h3>Results</h3> Eleven patients received deep-inspiration breath-hold RT (DIBH-RT), while four patients received free-breathing RT (FB-RT), where 4D-CT simulation was performed to define cardiac motion encompassment. To date, all patients have received hybrid ¹⁸FDG PET/MRI cardiac imaging and bloodwork at baseline and at one month after RT. Two patients have received their one-year follow-up ¹⁸FDG PET/MRI scan and bloodwork. At 1-month follow-up, a significant increase (10%) of ¹⁸FDG/PET myocardial uptake (meanSUV_bw) was detected at LAD territories (p = 0.04). A significant increase in mean ECV, measured with T1-mapping, was observed in slices of the apex (6%) and base (5%) were also detected (p < 0.02). A significant reduction of mean LV stroke volume (-7%) was also identified (p < 0.02). Insignificant changes of all blood work measurements at 1-month follow-up were reported. There was no detectable difference in any cardiac measure between patients who received DIBH-RT and FB-RT. For the two patients who had their one-year follow-ups, an increase in hs-CRP and ESR levels were detected compared to baseline, whereas global reduction of FDG uptake was seen. One patient had an increase of hs-TnT (up to 19ng/L) with left ventricle remodeling reported in echocardiography and a global increase of ECV. <h3>Conclusion</h3> ¹⁸FDG/PET myocardial uptake and functional MR, including SV and ECV were sensitive to changes at 1-month after breast cancer RT with findings suggesting an acute inflammatory response in the heart. One-year median follow-up imaging and bloodwork has been acquired for 2 of 15 patients thus far.

Machine Learning to Predict the Quality of a Left-Sided Whole Breast Radiotherapy Treatment Plan

<h3>Purpose/Objective(s)</h3> Develop a Support Vector Machine (SVM) model that uses dosimetric data to predict the quality of a breast radiotherapy treatment plan. <h3>Materials/Methods</h3> One hundred twenty left-sided breast cancer patients from a single institute were included in the study. They were treated with 15-fractions whole breast radiotherapy up to 40.05 Gy with a concomitant boost to deliver 48 Gy to the tumor bed. There was no treatment of lymph nodes. Dose was delivered with a fixed-beam treatment mode and delivered plans were manually created. For each patient, a second treatment plan was generated, using an in-house system for automated plan generation. The treating clinician evaluated the two available plans for each patient and assigned a sentence regarding the quality of the plan in the format of yes/no variable (well optimized plan i.e., "yes" or plan that can be further optimized i.e., "no"). A quantitative scoring tool (ST) already used by Orecchia et al was used to assign 0, 0.5 or 1 points for each involved OAR and PTVs depending on both the fulfilment of multiple DVH constraints and on achieved coverage level for PTVs. Four SVM models were trained using 216 plans (arbitrarily selected from the available 240) using: i) dose volume parameters for target and OARs of each plan, ii) ST and iii) the clinician's plan sentence. Training was performed through iterative optimization using ten Cross-validation folds with four models: a) Model 1 with the ST only, b) Model 2 with the difference between dose volume parameters and the DVH constraints, c) Model 3 with both information from models 1 and 2 and d) Model 4 with ST and dose volume parameter. All models had clinician's sentence as response variable. Finally, the 24/240 patients not used for training were used for final validation. Models' performances were assessed through confusion matrix parameters and multiclass ROC analyses on the training and independent validation set. <h3>Results</h3> The involved clinician refereed as "yes" 92 plans (77%) out of 120 and "no" the remaining 28 in the manual set; 79 plans (66%) were judged "yes" and 41 "no" in the automatic set. Results in terms of Accuracy (ACC), Positive Predicted Values (PPV), True Positive Rates (TPR) and Area under Curve (AUC) for the four models are presented in table 1. <h3>Conclusion</h3> Clinicians' judgements are crucial in daily plan evaluations. We have proposed supervised learning to predict if a plan will be considered by clinician well optimized or not. Results are encouraging and the tool could potentially become useful for aiding treatment planners and reducing clinicians' workload.

Dosimetric Comparison of Supine vs. Prone Position Utilizing Traditional Linac-Based Stereotactic Body Radiation Therapy for Accelerated Partial Breast Irradiation

<h3>Purpose/Objective(s)</h3> Our institution recently completed a pilot trial using stereotactic body radiation therapy (SBRT) for accelerated partial breast irradiation (APBI) on a traditional Linac delivering 30 Gy in 5 fractions. In this study, we compared dosimetry of patients treated in supine versus prone positions. <h3>Materials/Methods</h3> Patients enrolled on our recent pilot trial and additional post-accrual patients using the same SBRT technique were included. All patients had early-stage breast cancer, met the APBI ASTRO suitability criteria, and were treated on a traditional Linac. Treatment position, breast laterality and volume, BMI, and organs at risk (OAR) dosimetry were recorded. Prone treatments were delivered on a prone breast board using sliding window IMRT, and supine plans used either IMRT or partial arcs. All prone and 15 of 18 supine plans used free breathing technique (3 utilized deep inspiration breath-hold). CTV was 1 cm expansion from GTV. PTV was a 3 mm expansion from CTV and excluded skin surface+3 mm. Laterality was controlled for heart dosimetry. A small subset of patients was simulated in both supine and prone positions with associated radiation plans available for comparison. For unpaired data, unadjusted comparisons of means were performed using two-group t-test, and analysis of covariance was used for adjusted comparisons. For paired data, unadjusted comparisons were performed using the paired t-test, and adjusted comparisons used mixed models repeated measures analysis. Statistical tests were two-sided. <h3>Results</h3> This study included 35 patients with 36 treated plans. One patient had bilateral breast cancer. Of the 36 treated plans, 18 were supine (11 right-sided breast cancer, 7 left-sided) and 18 prone (8 right-sided, 10 left-sided). Eight patients had comparison plans in both positions. For patients with left-sided breast cancer, heart mean dose supine vs prone was 0.49 and 1.14 Gy, respectively (p < 0.001), and continued to be significant when controlling for BMI and treated breast volume. Mean heart dose was not different for right-sided patients supine vs prone, 0.36 vs 0.47 Gy, respectively (p = 0.870). Ipsilateral lung V1.5 Gy was higher for supine vs prone, 39.44 vs 29.89% (p=0.017). Max rib dose was higher for supine compared to prone, 28.29 vs 16.12 Gy (p<0.001). For the subset of patients with plans in both positions, mean heart dose continued to be lower for left-sided patients treated supine vs prone (p = 0.001). Ipsilateral lung V1.5 Gy and max dose to ribs were lower for prone with p values of 0.003 and <0.001, respectively. <h3>Conclusion</h3> Supine treatment provided heart dosimetry benefit for left-sided breast cancer patients compared to prone. Benefit was independent of BMI and breast volume. Prone position offered lower dose to ipsilateral lung and ribs. The results from this study can help determine the best treatment position based on patient-specific OAR concerns.

Preoperative Spirometry and BMI are Early Predictive Factors of the Cardiac and Lung Dose in Deep Inspiration Breath-Hold Radiotherapy

<h3>Purpose/Objective(s)</h3> This study aimed to investigate preoperative spirometry and BMI as early predictors of the mean heart and lung dose (MHD, MLD) in deep inspiration breath-hold (DIBH) radiotherapy. <h3>Materials/Methods</h3> Left-sided breast cancer patients underwent breast-conserving surgery followed by DIBH radiotherapy enrolled. Patients who were not available for preoperative spirometry were excluded. One hundred eligible patients were performed free-breathing (FB-) CT and DIBH-CT for plan comparison. We completed the correlative and multivariate analysis to develop the linear regression models for dose prediction. The residuals were calculated to explore the unpreferable subgroups and compare the prediction accuracy. <h3>Results</h3> Among the parameters, vital capacity (VC) and BMI showed the strongest negative correlation with MHD (r = –0.33) and MLD (r = –0.34), respectively. They were also significant in multivariate analysis (<i>P</i><0.001). Elderly and less VC were independent predictors of increasing absolute residuals (AR). The VC model showed no significant difference in AR compared to the model using the CT parameter of lung volume in FB (LV-FB): median AR of the LV-FB model vs. the VC model was 0.12 vs. 0.11 Gy (<i>P</i> = 0.79). On the other hand, the median AR of the MLD model was 0.38 Gy, showing no specific subgroups of larger AR. <h3>Conclusion</h3> Preoperative spirometry and BMI are significant predictors of MHD and MLD, respectively. Although elderly and low-VC patients may have larger predictive variations, spirometry might be a substitute for LV-FB as a predictor of MHD.

The effect of respiratory capacity for dose sparing in left-sided breast cancer irradiation with active breathing coordinator technique.

Background and aimA subsequent cardiac toxicity is deemed to be dose-dependent for left-sided breast cancer irradiation. This study aims to demonstrate the effect of respiratory capacity for dose sparing when the deep inspiration breath hold with Active Breathing Coordinator technique (ABC-DIBH) is used in left-sided breast cancer irradiation.Methods74 left-sided breast cancer patients, who received whole breast or post-mastectomy chest wall radiotherapy with ABC-DIBH between 2020 and 2021 in our center, were retrospectively reviewed in this study. CT scans of free breath (FB) and ABC-DIBH were done for each patient, and two treatment plans with a prescription dose of 5000 cGy/25 Fr were designed separately. The dose to heart, left anterior descending artery (LAD) and lungs was compared between FB and ABC-DIBH. The correlation between individual parameters (dose to organs at risk (OARs) and minimum heart distance (MHD)) was analyzed, and the effect of respiratory capacity for dose sparing was assessed.ResultsThe plans with ABC-DIBH achieved lower Dmean for heart (34.80%, P < 0.01) and LAD (29.33%, P < 0.01) than those with FB. Regression analysis revealed that both Dmean and D2 of heart were negatively correlated with MHD in the plans with FB and ABC-DIBH, which decreased with the increase in MHD by 37.8 cGy and 309.9 cGy per 1mm, respectively. Besides, a lower Dmean of heart was related to a larger volume of ipsilateral lung in plans with FB. With the increase in volume of ipsilateral lung, the linear correlation was getting weaker and weaker until the volume of ipsilateral lung reached 1700 cc. Meanwhile, a negative linear correlation between Dmean of LAD and MHD in plans with FB and ABC-DIBH was observed, whose slope was 162.5 and 135.9 cGy/mm, respectively. Furthermore, when the respiratory capacity of ABC-DIBH reached 1L, and the relative ratio (ABC-DIBH/FB) reached 3.6, patients could obtain the benefit of dose sparing. The larger difference in respiratory capacity had no significant effect in the larger difference of MHD, Dmean of heart and Dmean of LAD between FB and ABC-DIBH.ConclusionThis study demonstrates the sufficiently good effect of ABC-DIBH when utilizing for cardiac sparing. It also reveals the correlations among individual parameters and the effect of respiratory capacity for dose sparing. This helps take optimal advantage of the ABC-DIBH technique and predict clinical benefits.

Accuracy and potential improvements of surface-guided breast cancer radiotherapy in deep inspiration breath-hold with daily image-guidance

Objective. Radiotherapy of left-sided breast cancer in deep inspiration breath-hold (DIBH) reduces the heart dose. Surface guided radiotherapy (SGRT) can guide the DIBH, but the accuracy is subject to variations in the chest wall position relative to the patient surface. Approach. In this study, ten left-sided breast cancer patients received DIBH radiotherapy with tangential fields in 15–18 fractions. After initial SGRT setup in free breathing an orthogonal MV/kV image pair was acquired during SGRT-guided breath-hold. The couch was corrected to align the chest wall during another breath-hold, and a new SGRT reference surface was acquired for the gating. The chest wall position error during treatment was determined from continuous cine MV images in the imager direction perpendicular to the cranio-caudal direction. A treatment error budget was made with individual contributions from the online registration of the setup MV image, the difference in breath-hold level between setup imaging and SGRT reference surface acquisition, the SGRT level during treatment, and intra-fraction shifts of the chest wall relative to the SGRT reference surface. In addition to the original setup protocol (Scenario A), SGRT was also simulated with better integration of image-guidance by capturing either the new reference surface (Scenario B) or the SGRT positional signal (Scenario C) simultaneously with the setup MV image, and accounting for the image-guided couch correction by shifting the SGRT reference surface digitally. Main results. In general, the external SGRT signal correlated well with the internal chest wall position error (correlation coefficient >0.7 for 75% of field deliveries), but external-to-internal target position offsets above 2 mm occasionally occurred (13% of fractions). The PTV margin required to account for the treatment error was 3.5 mm (Scenario A), 3.4 mm (B), and 3.1 mm (C). Significance. Further integration of SGRT with image-guidance may improve treatment accuracy and workflow although the current study did not show large accuracy improvements of scenario B and C compared to scenario A.

Integrated scoring approach to assess radiotherapy plan quality for breast cancer treatment.

BackgroundProposal of an integrated scoring approach assessing the quality of different treatment techniques in a radiotherapy planning comparison. This scoring method incorporates all dosimetric indices of planning target volumes (PTVs) as well as organs at risk (OARs) and provides a single quantitative measure to select an ideal plan.Materials and methodsThe radiotherapy planning techniques compared were field-in-field (FinF), intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), hybrid IMRT (H-IMRT), and hybrid VMAT (H-VMAT). These plans were generated for twenty-five locally advanced left-sided breast cancer patients. The PTVs were prescribed a hypofractionation dose of 40.5 Gy in 15 fractions. The integrated score for each planning technique was calculated using the proposed formula.ResultsAn integrated score value that is close to zero indicates a superior plan. The integrated score that incorporates all dosimetric indices (PTVs and OARs) were 1.37, 1.64, 1.72, 1.18, and 1.24 for FinF, IMRT, VMAT, H-IMRT, and H-VMAT plans, respectively.ConclusionThe proposed integrated scoring approach is scientific to select a better plan and flexible to incorporate the patient-specific clinical demands. This simple tool is useful to quantify the treatment techniques and able to differentiate the acceptable and unacceptable plans.

Deep inspiration breath-hold radiation therapy in left-sided breast cancer patients: a single-institution retrospective dosimetric analysis of organs at risk doses

BackgroundRadiotherapy can induce cardiac injury in left-sided breast cancer cases. Cardiac-sparing irradiation using the deep inspiration breath-hold (DIBH) technique can achieve substantial dose reduction to vulnerable cardiac substructures compared with free breathing (FB). This study evaluated the dosimetric differences between both techniques at a single institution.MethodsFrom 2017 to 2019, 130 patients with left-sided breast cancer underwent breast-conserving surgery (BCS; n = 121, 93.1%) or mastectomy (ME; n = 9, 6.9%) along with axillary lymph node staging (n = 105, 80.8%), followed by adjuvant irradiation in DIBH technique; adjuvant systemic therapy was included if applicable. 106 (81.5%) patients received conventional and 24 (18.5%) hypofractionated irradiation. Additionally, 12 patients received regional nodal irradiation. Computed tomography (CT) scans in FB and DIBH position were performed for all patients. Intrafractional 3D position monitoring of the patient surface in deep inspiration and breath gating was performed using Sentinel and Catalyst HD 3D surface scanning systems (C-RAD, Catalyst, C‑RAD AB, Uppsala, Sweden). Individual coaching and determination of breathing amplitude during the radiation planning CT was performed. Three-dimensional treatment planning was performed using standard tangential treatment portals (6 or 18 MV). The delineation of cardiac structures and both lungs was done in both the FB and the DIBH scan.ResultsAll dosimetric parameters for cardiac structures were significantly reduced (p < 0.01 for all). The mean heart dose (Dmean) in the DIBH group was 1.3 Gy (range 0.5–3.6) vs. 2.2 Gy (range 0.9–8.8) in the FB group (p < 0.001). The Dmean for the left ventricle (LV) in DIBH was 1.5 Gy (range 0.6–4.5), as compared to 2.8 Gy (1.1–9.5) with FB (p < 0.001). The parameters for LV (V10 Gy, V15 Gy, V20 Gy, V23 Gy, V25 Gy, V30 Gy) were reduced by about 100% (p < 0.001). The LAD Dmean in the DIBH group was 4.1 Gy (range 1.2–33.3) and 14.3 Gy (range 2.4–37.5) in the FB group (p < 0.001). The median values for LAD such as V15 Gy, V20 Gy, V25 Gy, V30 Gy, and V40 Gy decreased by roughly 100% (p < 0.001). An increasing volume of left lung in the DIBH position resulted in dose sparing of cardiac structures.ConclusionFor all ascertained dosimetric parameters, a significant dose reduction could be achieved in DIBH technique.

The effect of using virtual bolus on VMAT plan quality for left-sided breast cancer patients

In breast cancer radiotherapy treatment with Volumetric Modulated Arc Therapy (VMAT), the respiratory motion may lead to underdosing of the target and overdosing of critical organs such as the heart and lungs. This study aims to investigate the effect of using Virtual Bolus with different thicknesses on VMAT plan quality for patients with 20 advanced left-sided breast cancers. The result of the study showed that using Virtual Bolus for VMAT treatment planning is a viable method to avoid any missing target coverage.

Development of deep learning chest X-ray model for cardiac dose prediction in left-sided breast cancer radiotherapy

Deep inspiration breath-hold (DIBH) is widely used to reduce the cardiac dose in left-sided breast cancer radiotherapy. This study aimed to develop a deep learning chest X-ray model for cardiac dose prediction to select patients with a potentially high risk of cardiac irradiation and need for DIBH radiotherapy. We used 103 pairs of anteroposterior and lateral chest X-ray data of left-sided breast cancer patients (training cohort: n = 59, validation cohort: n = 19, test cohort: n = 25). All patients underwent breast-conserving surgery followed by DIBH radiotherapy: the treatment plan consisted of three-dimensional, two opposing tangential radiation fields. The prescription dose of the planning target volume was 42.56 Gy in 16 fractions. A convolutional neural network-based regression model was developed to predict the mean heart dose (∆MHD) reduction between free-breathing (MHDFB) and DIBH. The model performance is evaluated as a binary classifier by setting the cutoff value of ∆MHD > 1 Gy. The patient characteristics were as follows: the median (IQR) age was 52 (47–61) years, MHDFB was 1.75 (1.14–2.47) Gy, and ∆MHD was 1.00 (0.52–1.64) Gy. The classification performance of the developed model showed a sensitivity of 85.7%, specificity of 90.9%, a positive predictive value of 92.3%, a negative predictive value of 83.3%, and a diagnostic accuracy of 88.0%. The AUC value of the ROC curve was 0.864. The proposed model could predict ∆MHD in breast radiotherapy, suggesting the potential of a classifier in which patients are more desirable for DIBH.

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.

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. For 25patients who underwent CT simulation in deep inspiration breath-hold (DIBH), three treatment plans were generated: one using athree-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. All plans fulfilled the criterium for PTV V95% ≥ 95%. The PTV coverage, homogeneity, and conformity indices were significantly better for VMAT-DIBH. VMAT showed asignificantly 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 10,000PYs, 2.55 per 10,000PYs, and 4.48 per 10,000PYs (p < 0.001), compared to 40.29 per 10,000PYs, 15.62 per 10,000PYs, and 23.44 per 10,000PYs for ARC-DIBH 3A plans and 41.12 per 10,000PYs, 15.59 per 10,000PYs, and 22.73 per 10,000PYs for ARC-DIBH 4A plans. Both techniques provided negligibly low NTCPs for all OARs. The study shows that VMAT-DIBH provides better OAR sparing against high doses. However, the large low-dose-bath (≤ 5 Gy) is still aconcern due to the fact that alarger volume of normal tissues exposed to lower doses may increase aradiation-induced risk of secondary cancer.

A Critical Overview of Predictors of Heart Sparing by Deep-Inspiration-Breath-Hold Irradiation in Left-Sided Breast Cancer Patients.

Radiotherapy represents an essential part of the therapeutic algorithm for breast cancer patients after conservative surgery. The treatment of left-sided tumors has been associated with a non-negligible risk of developing late-onset cardiovascular disease. The cardiac risk perception has especially increased over the last years due to the prolongation of patients' survival owing to the advent of new drugs and an ever earlier cancer detection through screening programs. Improvements in radiation delivery techniques could reduce the treatment-related heart toxicity. The deep-inspiration-breath-hold (DIBH) irradiation is one of the most advanced treatment approaches, which requires specific technical equipment and uses inspiration to displace the heart from the tangential radiation fields. However, not all patients benefit from its use. Moreover, DIBH irradiation needs patient compliance and accurate training. Therefore, such a technique may be unjustifiably cumbersome and time-consuming as well as unnecessarily expensive from a mere healthcare cost point of view. Hence the need to early select only the true beneficiaries while tailoring more effective heart-sparing techniques for the others and streamlining the workflow, especially in high-volume radiation oncology departments. In this literature overview, we collected some possible predictors of cardiac dose sparing in DIBH irradiation for left breast treatment in an effort to provide an easy-to-consult summary of simple instruments to insiders for identifying patients actually benefitting from this technique. We critically reviewed the reliability and weaknesses of each retrieved finding, aiming to inspire new insights and discussions on this much-debated topic.

A comprehensive dosimetric comparison in adjuvant radiotherapy for various regional lymph node irradiations of left-side breast cancer using volumetric modulated arc therapy

Breast cancer is the most common cancer among women worldwide. The purpose of this study was to investigate the dosimetric parameters of critical organs for various irradiation ranges in the treatment of left-side breast cancer. The irradiation planning target volume (PTV) range in this research was divided into four groups: whole breast irradiation (group 1), whole breast with SCF irradiation (group 2), whole breast with SCF and AXLN irradiation (group 3), and whole breast with SCF, AXLN and IMN irradiation (group 4). Each group included 20 patients. We analyzed the dose parameters for the various irradiation ranges in the treatment plans retrospectively. The prescription dose was 45 Gy in 25 fractions to the PTV. In terms of the left lung, the mean dose in the four groups was 7.29 ± 1.04 Gy in group 1, 8.94 ± 2.13 Gy in group 2, 10.20 ± 1.44 Gy in group 3, and 11.44 ± 1.20 Gy in group 4. The average V5Gy, V10Gy, and V20Gy values of the left lung and whole lungs for group 1 and group 2 plans, group 1 and group 3 plans, and group 1 and group 4 plans were statistically significantly different. In terms of the heart, the average dose was 2.50 ± 0.47 Gy, 2.58 ± 0.74 Gy, 3.00 ± 0.43 Gy, and 3.97 ± 1.14 Gy in the plans of groups 1 to 4, respectively. The average V5Gy of the heart was 6.90 ± 2.26 Gy in group 1, 7.75 ± 2.58 Gy in group 2, 8.43 ± 2.10 Gy in group 3, and 13.89 ± 2.88 Gy in group 4. The study demonstrated various RT irradiation areas for left-side breast cancer patients. The dosimetric results of this research showed that an extensive volume with regional nodal irradiation may have the potential to increase the risks of radiation pneumonitis and heart disease. The comprehensive dosimetric analysis performed in this study will be helpful for clinical oncologists and medical physicists in terms of clarifying treatment plans to identify the results of any planned irradiation.

Comparison of Heart and Lung Doses According to Tumor Bed Boost Techniques in Early-Stage Left-Sided Breast Cancer: Simultaneous Integrated Boost versus Sequential Boost.

Background and Objectives: The boost dose to the tumor bed after whole breast irradiation (WBI) can be divided into sequential boost (SEQ) and simultaneous integrated boost (SIB). SIB using modern radiation therapy (RT) techniques, such as volumetric modulated arc therapy, allow the delivery of a highly conformal dose to the target volume and has a salient ability to spare at-risk organs. This study aimed to compare the radiation dose delivered to the heart and lungs according to boost technique and tumor bed location. Materials and Methods: RT planning data of 20 patients with early-stage left-sided breast cancer were used in this study. All patients were treated with volumetric modulated arc therapy after breast-conserving surgery with a sentinel lymph node biopsy. For each patient, two different plans, whole breast irradiation with simultaneous integrated boost (WBI-SIB) and sequential boost after WBI (WBI-SEQ), were generated. To compare the dose received by each organ at risk (OAR), dose-volume histogram data were analyzed. The mean dose (Dmean) and volume of each organ that received x Gy (Vx) were calculated and compared. Results: For the heart, the V10 was lower for the WBI-SIB plan than for the WBI-SEQ plan (5.223 ± 1.947% vs. 6.409 ± 2.545%, p = 0.008). For the left lung, the V5 was lower in the WBI-SIB plan than for the WBI-SEQ plan (27.385 ± 3.871% vs. 32.092 ± 3.545%, p < 0.001). The Dmean for the heart and left lung was lower for the WBI-SIB plan than for the WBI-SEQ plan (heart: 339.745 ± 46.889 cGy vs. 413.030 ± 52.456 cGy, p < 0.001; left lung: 550.445 ± 65.094 cGy vs. 602.270 ± 55.775 cGy, p < 0.001). Conclusions: The WBI-SIB plan delivered lower radiation doses to the heart and left lung than the WBI-SEQ plan in terms of Dmean and low-dose volume in hypofractionated RT of early-stage left-sided breast cancer patients. Furthermore, a large radiation dose per day may be advantageous, considering the radiobiologic aspects of breast cancer. Long-term follow-up data are needed to determine whether the dosimetric advantages of the WBI-SIB plan can lead to clinically improved patient outcomes and reduced late side effects.

Incidental irradiation of the regional lymph nodes during deep inspiration breath-hold radiation therapy in left-sided breast cancer patients: a dosimetric analysis

BackgroundRadiotherapy using the deep inspiration breath-hold (DIBH) technique compared with free breathing (FB) can achieve substantial reduction of heart and lung doses in left-sided breast cancer cases. The anatomical organ movement in deep inspiration also cause unintended exposure of locoregional lymph nodes to the irradiation field.MethodsFrom 2017–2020, 148 patients with left-sided breast cancer underwent breast conserving surgery (BCS) or mastectomy (ME) with axillary lymph node staging, followed by adjuvant irradiation in DIBH technique. Neoadjuvant or adjuvant systemic therapy was administered depending on hormone receptor and HER2-status.CT scans in FB and DIBH position with individual coaching and determination of the breathing amplitude during the radiation planning CT were performed for all patients. Intrafractional 3D position monitoring of the patient surface in deep inspiration and gating was performed using Sentinel and Catalyst HD 3D surface scanning systems (C-RAD, Catalyst, C-RAD AB, Uppsala, Sweden). Three-dimensional treatment planning was performed using standard tangential treatment portals (6 or 18 MV). The delineation of ipsilateral locoregional lymph nodes was done on the FB and the DIBH CT-scan according to the RTOG recommendations.ResultsThe mean doses (Dmean) in axillary lymph node (AL) level I, II and III in DIBH were 32.28 Gy (range 2.87–51.7), 20.1 Gy (range 0.44–53.84) and 3.84 Gy (range 0.25–39.23) vs. 34.93 Gy (range 10.52–50.40), 16.40 Gy (range 0.38–52.40) and 3.06 Gy (range 0.21–40.48) in FB (p < 0.0001). Accordingly, in DIBH the Dmean for AL level I were reduced by 7.59%, whereas for AL level II and III increased by 22.56% and 25.49%, respectively.The Dmean for the supraclavicular lymph nodes (SC) in DIBH was 0.82 Gy (range 0.23–4.11), as compared to 0.84 Gy (range 0.22–10.80) with FB (p = 0.002). This results in a mean dose reduction of 2.38% in DIBH.The Dmean for internal mammary lymph nodes (IM) was 12.77 Gy (range 1.45–39.09) in DIBH vs. 11.17 Gy (range 1.34–44.24) in FB (p = 0.005). This yields a mean dose increase of 14.32% in DIBH.ConclusionsThe DIBH technique may result in changes in the incidental dose exposure of regional lymph node areas.

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 Comparison of Three Different Breath Hold Techniques Used for Reducing Cardiac Dose for Patients Receiving Left-Sided Breast Cancer Radiation Therapy

Purpose: Cardiac toxicity is a major concern for left-sided breast cancer patients receiving radiation therapy (RT). Different breath-hold techniques may be used to reduce cardiac dose including voluntary deep inspiration breath hold (vDIBH), the Elekta Active Breathing Coordinator (ABC), and the AlignRT system from VisionRT. The purpose of this study is to evaluate the differences in heart position and mean heart dose for these three techniques during RT of left-sided breast cancer patients.

Deep inspiratory breath-hold radiotherapy for left-sided breast cancer: Initial experience with Active Breathing Coordinator™ in a regional hospital.

Deep inspiratory breath-hold (DIBH) has become standard in radiotherapy for left-sided breast cancer to reduce the heart dose. This study evaluated breath-hold stability and reproducibility using Elekta's Active Breathing Coordinator™ (ABC) and its effectiveness and feasibility in left-sided breast cancer patients undergoing radiotherapy. Eligible patients were planned with free breathing (FB) and DIBH protocols. DIBH treatment was considered if the mean heart dose (MHD) was ≥2 Gy on the FB plan. Those who proceeded with DIBH treatment were enrolled for the pilot study. Electronic portal images of DIBH treatment beams were taken using the movie-exposure mode for breath-hold stability and reproducibility analysis. DIBH effectiveness in heart dose reduction and impact on simulation and treatment durations were compared with FB protocol. Out of 56 eligible patients, 15 proceeded with DIBH treatment. The mean difference of patient setup within a single breath-hold was 0.4 mm; between different breath-holds of the same beam 1.1 mm and between different days 2.6 mm. DIBH reduced the MHD by 47% and the mean left anterior descending artery (LAD) dose by 35%. DIBH took longer time than FB in simulation and treatment. At least 14% of the eligible patients did not tolerate DIBH during simulation. ABC leads to stable and reproducible breath-holds and results in significant heart dose reductions. It may not be tolerated by all patients and has resource implications.

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.