Left-sided Breast Cancer Patients Research Articles

Proton therapy reduces the effective dose to immune cells in breast cancer patients.

The effective dose to circulating immune cells (EDIC) is associated with survival in lung and esophageal cancer patients. This study aimed to evaluate the benefit of intensity-modulated proton therapy (IMPT) for EDIC reduction as compared to volumetric modulated arc therapy (VMAT) in patients with locally advanced breast cancer (BC). Ten BC patients treated with locoregional VMAT after breast-conserving surgery were included. Mean dose to the heart (MHD), lungs (MLD), and liver (MlD), as well as the integral dose to the body (ITD), were retrieved, and we calculated EDIC as 0.12 × MLD + 0.08 × MHD + 0.15 × 0.85 × √(n/45) × MlD + (0.45 + 0.35 × 0.85 × √(n/45)) × ITD/(62 × 103), where n is the number of fractions. EDIC was compared between VMAT and IMPT plans. Median EDIC was reduced from 3.37 Gy (range: 2.53-5.99) with VMAT to 2.13 Gy (1.31-3.77) with IMPT (p < 0.01). For left-sided BC patients, EDIC was reduced from 3.15 Gy (2.53-3.78) with VMAT to 1.65 Gy (1.31-3.77) with IMPT (p < 0.01). For right-sided BC patients, EDIC was reduced from 5.60 Gy (5.06-5.99) with VMAT to 3.38 Gy (3.10-3.77) with IMPT (p < 0.01). Right-sided BC patients had ahigher EDIC irrespective of the technique. Integral dose reduction was the main driver of EDIC reduction with IMPT and was associated with lung sparing for left-sided BC patients or liver sparing for right-sided BC patients. IMPT significantly reduced EDIC in BC patients undergoing locoregional adjuvant radiotherapy. Integral total dose reduction, associated with improved lung sparing in left-sided BC patients or liver sparing in right-sided BC patients, mainly drove EDIC reduction with IMPT. The emergence of dynamic models taking into account the circulatory kinetics of immune cells may improve the accuracy of the estimate of the dose received by the immune system compared to calculation of the EDIC, which is based solely on static dosimetric data.

Prospective Randomized Trial Comparing 2 Devices for Deep Inspiration Breath Hold Management in Breast Radiation Therapy: Results of the BRAVEHeart Trial

Aims: The BRAVEHeart trial prospectively randomized left-sided breast cancer patients to one of two deep inspiration breath hold (DIBH) biofeedback devices: a novel chest surface tracking system and an abdominal block tracking system. The primary hypothesis was that the accuracy of chest tracking would be higher than that of abdominal tracking as the chest is a more direct surrogate of the breast target.Methods: Left-sided breast cancer patients were treated in DIBH with IMRT delivery. Patients were randomized to either the novel chest surface system or abdominal block system for active management of breath hold with visual feedback. On both trial arms the unallocated system monitored passively.239,296 cine EPID images were analyzed retrospectively to extract the chest wall position. Treatment accuracy was quantified as the deviation of the internal chest wall during treatment relative to the planned position from the digitally reconstructed radiograph. The correlation between motion of the external surrogate and internal chest wall was calculated per breath hold. Ease of use was assessed with questionnaires for both radiation therapists and patients and appointment length recorded.Results: Data from 26 participants were available for analysis. No difference was found in delivered treatment accuracy between arms. Across all patients and fractions, the median correlation between internal chest wall movement and external surrogate was 0.69 for the chest surface and 0.17 for the abdominal block. Patients found it easy to follow visual feedback from both systems. No difference was found in appointment length between arms.Conclusions: No statistical evidence was found for superior treatment accuracy, satisfaction or appointment length for the novel chest surface tracking device compared to the abdominal block system. During DIBH, the median per-breath hold correlation of internal chest wall movement to the motion of the chest surface was higher than the median correlation of the abdominal block to the chest surface.

Cardiac markers in left-sided breast cancer patients receiving adjuvant radiotherapy: a prospective study.

To investigate the association between radiotherapy (RT) and cardiac biomarkers in women with left-sided breast cancer. This prospective observational study recruited patients with stage I-III left-sided breast cancer without coronary heart disease who required adjuvant RT. High-sensitivity troponin I(hsTnI), N-terminal pro-brain natriuretic peptide(NT-proBNP), and high-sensitivity C-reactive protein(hsCRP) levels were measured pre-RT, immediately after RT, and 3 months post-RT. Cardiac-sparing RT techniques were utilized (Field-in-Field IMRT/VMAT ± voluntary deep inspiration breath-hold). Statistical analyses were performed using non-parametric tests and multivariable quantile regression (QR). One hundred five patients completed the study, with 63 evaluable at three months post-RT. Pre- and post-RT biomarkers showed no significant differences. Median pre-RT and post-RT values were: hsTnI (0.012ng/mL; 0.012ng/mL), hsCRP (3.1mg/L; 2.8mg/L), and NT-proBNP (59pg/mL; 45pg/mL). Three months post-RT, hsTnI, hsCRP and NT-proBNP levels also showed no significant differences. Multivariable QR revealed no association between heart Dmean [median(IQR): 2.87Gy (2.05-3.94)] and post-RT biomarkers. Age and BMI were associated with hsCRP and NT-proBNP, respectively. hsTnI, NT-proBNP, and hsCRP are not correlated with contemporary low cardiac exposure in left-sided breast cancer patients treated with contemporary RT techniques.

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.

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.

Analysis of multicatheter interstitial brachytherapy: Accelerated partial breast irradiation in a retrospective cohort of early-stage breast cancer patients

To determine cardiac dose received by patients treated with high dose rate interstitial brachytherapy. Patients with early-stage, node negative breast cancer can be treated using multi-catheter interstitial brachytherapy accelerated partial breast irradiation (MIB-APBI), with the benefit of reduced treatment volumes and favorable toxicity. We conducted a retrospective review of left-sided breast cancer patients treated using MIB-APBI at our institution since 2014. The mean heart dose (MHD) was calculated using the Oncentra 3.2 planning system. The minimum distance between the planning target volume (PTVeval) and heart contour was measured manually. 81 patients were included. The upper outer quadrant was the most common site. The MHD was 97.8 cGy (EQD2a/b=2) (range 22-229 cGy). MHD significantly correlated with the closest distance between PTVeval and heart contour (correlation coefficient -0.823, p <0.001); size of PTVeval (cc) and quadrant location did not. Appropriately selected women with early-stage, low-risk, left-sided breast cancer who received MIB-APBI had acceptable MHD. There was a strong correlation between the distance of PTVeval and MHD. Quadrant breast tumor is in cannot be used as a surrogate for MHD in brachytherapy. Our findings contribute to the growing evidence of the utility and safety of MIB-APBI.

Locoregional breast radiotherapy including IMN: optimizing the dose distribution using an automated non-coplanar VMAT-technique

Background Volumetric Modulated Arc Therapy (VMAT) offers better conformity, homogeneity and sparing of the heart and ipsilateral lung for locoregional radiotherapy in left-sided breast cancer compared to three-dimensional conformal radiotherapy (3D-CRT). However, conventional coplanar VMAT (cVMAT) can result in higher doses to the normal tissue on the contralateral side. This study investigates a non-coplanar VMAT-technique (ncVMAT) to mitigate this issue. Material and methods CT series of 20 left sided breast cancer patients were included for planning of locoregional breast radiotherapy including internal mammary nodes (IMN). Three treatment plans; 3D-CRT, cVMAT and ncVMAT, were generated for each patient with a prescription dose of 40.05 Gy in 15 fractions. Both VMAT-techniques consisted of a single arc in the axial plane, while ncVMAT included an additional arc in the sagittal plane. All plans were optimized to cover the clinical target volume (CTV) by 38.05 Gy for the breast and 36.05 Gy for lymph nodes, with as low as possible dose to organs at risk. Results Full CTV coverage was achieved for all plans. Both cVMAT and ncVMAT delivered more conformal and homogeneous target doses than 3D-CRT. Doses to the heart and ipsilateral lung were significantly lower with ncVMAT compared to both cVMAT and 3D-CRT. ncVMAT reduced doses to both the contralateral breast and lung compared to cVMAT and achieved levels similar to 3D-CRT for the contralateral breast and moderately higher doses for the contralateral lung. Delivery of high doses (>30 Gy) to the contralateral side was completely avoided with ncVMAT, contrary to the results for cVMAT and 3D-CRT. Conclusion ncVMAT reduced doses to the heart and ipsilateral lung as compared to both cVMAT and 3D-CRT. All contralateral dose metrics were reduced with the novel ncVMAT technique compared to cVMAT, and the mean contralateral breast doses were similar to 3D-CRT.

A Retrospective Dosimetric Study in Breast Cancer Patients Who Received Conformal Radiation Therapy for Achievability of Recommended Dose Constraints of RTOG, DBCG, EORTC for Lung and Heart

In India, carcinoma of breast is the commonest malignancy among women. In multidisciplinary approach of its management, radiotherapy (RT) is an important component. Different cooperative groups have defined dose constraints to lungs and heart to minimize these late side effects such as radiation pneumonitis and coronary artery disease. To assess the achievability of dose constraints given for lung and heart by RTOG, EORTC and DBCG in our cohort of breast cancer patients who underwent conformal radiation therapy to chest wall / breast along with supraclavicular nodal region. This retrospective dosimetric study included all breast cancer patients who underwent conformal radiation in our institute from Jan 2021 to Dec 2022 and was treated with a dose of 40 Gy in 15 fractions. A total of 302 patients (162 - Left sided, 140 - Right sided) were in the study cohort. Majority of them received RT with 3DCRT with FiF (266 patients) and 36 patients received RT by VMAT technique. Respiratory gating was done in left sided breast cancer by DIBH for 46.2 % of patients due to COVID pandemic during this period. Our analysis showed that for the ipsilateral lung, EORTC (77.8%) dose constraints were easy to achieve followed by DBCG (65.2%) and RTOG (61.9 %). For the heart constraints in left sided breast cancer patients, easily achievable constraints were by DBCG (91.9 %) followed by RTOG (66.6 %) and EORTC (53.1%). The DBCG constraints of Dmean <5 Gy was more liberal than any other recommendations. All the dose constraint recommendations were easily achieved for heart in right sided breast cancer patients, by more than 90 % of the population. Usage of respiratory gating with DIBH technique improves the rates of achievability of lung constraints in 56 (74.6%) out of 75 patient and heart constraints in 54 (72 %) out of 75 patients. Our institutional policy is to treat chest wall / breast along with supraclavicular nodal chain in case of NACT or T3/T4 disease and this could have been the reason why we were unable to achieved the dose constraints recommended. The DBCG dose constraint recommendations for heart was achieved in the left chest wall treatment in majority of women and EORTC was best achieved for ipsilateral lung. All heart dose constraint recommendations were achieved for right chest wall treatment. Respiratory gating improves achievability rates of the recommendations. It is difficult to achieve all the dose constraints as recommended by different cooperative groups as there is variation among them.

Comparison of Early Outcomes of Stereotactic Accelerated Partial Breast Irradiation vs. Volumetric Modulated Arc Therapy-Based FAST-FORWARD Whole Breast Irradiation for Breast Cancer

Despite evidence supporting APBI from 8 published prospective randomized trials enrolling over 10,000 women, the uptake of APBI in clinical practice is surprisingly low. This is being exacerbated by a new, convenient, and safe shortened WBI schedule. Here, we report the dosimetric and early outcome analyses of the first >1000 patients treated at our institution since the first adoption of stereotactic APBI and the ultra-hypofractionated WBI regimen. From 2016 to 2022, 801 women with breast cancers in the suitable or cautionary categories according to the ASTRO APBI consensus panel guidelines, received 30 Gy in 5 fractions (92%) either using a robotic stereotactic radiation system (83%) or stereotactic volumetric-based arc therapy (VMAT, 17%). Between 2020 and 2022, 468 women, who were not candidates for APBI and not undergoing any regional irradiation received 26 Gy in 5 fractions using VMAT to the whole breast with the addition of cardiac sparing technique in left-sided breast cancer patients. Tumor bed boosts were delivered in 99% of FF-WBI patients. We evaluated dose-volume histogram parameters for target volumes and organs-at-risk and radiation-related toxicities during RT or within 6 months after the end of RT. Target volume coverage was acceptable in both groups, with mean 96% of the target volumes receiving 95% of the prescribed doses and 0 cm3 within target volumes exceeding 105% of the prescribed doses. S-APBI resulted in small, but statistically significant, reductions in the radiation dose delivered to the ipsilateral breast, contralateral breast, lungs, heart, and coronary artery compared with FF-WBI. Comparing WBI to APBI, the mean contralateral breast dose, ipsilateral lung V20 Gy, mean contralateral lung dose, and mean heart dose, were reduced by 89%, 78%, 73%, and 29%, respectively. With median follow-up periods of 32 months for s-APBI and 19 months for FF-WBI, acute toxicity was assessable in all patients. The risks of any grade acute toxicity were 21% for s-APBI and 25% for FF-WBI (p = .117). Among them, grade 2 rates were 1.3% in both groups and no severe toxicity has been reported. We found s-APBI and VMAT-based FF WBI were associated with favorable dosimetric and acute toxicity profiles. However, considering significantly less irradiated volume in the breast, lungs, and heart, APBI with advanced available technique options should be considered over any WBI-based approach for patients at low risk for local recurrence.

Changes in myocardial blood flow in a canine model of left sided breast cancer radiotherapy.

Left-sided breast cancer patients receiving adjuvant radiotherapy are at risk for coronary artery disease, and/or radiation mediated effects on the microvasculature. Previously our laboratory demonstrated in canines with hybrid 18FDG/PET a progressive global inflammatory response during the initial one year following treatment. In this study, the objective is to evaluate corresponding changes in perfusion, in the same cohort, where resting myocardial blood flow (MBF) was quantitatively measured. In five canines, Ammonia PET (13NH3) derived MBF was measured at baseline, 1-week, 1, 3, 6 and 12-months after cardiac external beam irradiation. MBF measurements were correlated with concurrent 18FDG uptake. Simultaneously MBF was measured using the dual bolus MRI method. MBF was significantly increased at all time points, in comparison to baseline, except at 3-months. This was seen globally throughout the entire myocardium independent of the coronary artery territories. MBF showed a modest significant correlation with 18FDG activity for the entire myocardium (r = 0.51, p = 0.005) including the LAD (r = 0.49, p = 0.008) and LCX (r = 0.47, p = 0.013) coronary artery territories. In this canine model of radiotherapy for left-sided breast cancer, resting MBF increases as early as 1-week and persists for up to one year except at 3-months. This pattern is similar to that of 18FDG uptake. A possible interpretation is that the increase in resting MBF is a response to myocardial inflammation.

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.

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

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

Dosimetric comparison of three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and volumetric-modulated arc therapy for free-breathing whole-breast irradiation: A planning study.

Currently, recommended heart dose constraints are difficult to meet in whole-breast irradiation (WBI) for left-sided breast cancer patients, who cannot be treated with the deep inspiration breath hold. We performed a radiotherapy planning study to establish if the use of intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) allows for better sparing of the heart and its subvolumes than the three-dimensional conformal radiation therapy (3D-CRT), and how these attempts affect the dose delivered to the other organs. A total of 17 left-sided and 10 right-sided consecutive patients treated with free-breathing WBI were retrospectively included. The 3D-CRT, IMRT, and VMAT plans were generated. Several dose-volume parameters and plan quality indices were compared, separately for the left- and right-sided plans. All the techniques fulfilled the planning objectives. In the left-sided plans, there was no heart or left ventricle dose reduction with IMRT, nor with VMAT; the maximum dose in the left anterior descending coronary artery was reduced with VMAT (P = 0.005); V5 for the contralateral breast, contralateral lung, and total-body increased markedly in VMAT, and for the ipsilateral lung (V5IL) also in IMRT, compared with 3D-CRT (P < 0.001). In the right-sided plans, the V5 values, except for V5IL, did not differ between the three techniques. IMRT and VMAT had a limited heart-sparing benefit in the left-sided free-breathing WBI, at the cost of increased low-dose volumes, measured by V5. The low-dose volumes are not increased by IMRT or VMAT in the right-sided WBI, where heart sparing is not a problem, but the attempts to reduce cardiac doses in the left-sided WBI increase them.

Current Cardioprotective Strategies for the Prevention of Radiation-Induced Cardiotoxicity in Left-Sided Breast Cancer Patients.

Breast cancer (BC) is the most common malignancy in females, accounting for the majority of cancer-related deaths worldwide. There is well-established understanding about the effective role of radiotherapy (RT) in BC therapeutic strategies, offering a better local-regional control, prolonged survival, and improved quality of life for patients. However, it has been proven that conventional RT modalities, especially in left-sided BC cases, are unable to avoid the administration of high RT doses to the heart, thus resulting in cardiotoxicity and promoting long-term cardiovascular diseases (CVD). Recent radiotherapeutic techniques, characterized by dosimetric dose restrictions, target volume revision/modifications, an increased awareness of risk factors, and consistent follow-ups, have created an advantageous context for a significant decrease inpost-RT CVD incidence. This review presents the fundamental role of current cardioprotective strategies in the prevention of cardiotoxic effects in left-BCRT. A literature search was conducted up to January 2023 using the Cochrane Central Register of Controlled Trials and PubMed Central databases. Our review refers to new radiotherapeutic techniques carried out on patients after BC surgery. Specifically, a dose evaluation of the heart and left anterior descending coronary artery (LADCA) was pointed out for all the included studies, depending on the implemented RT modality, bed positioning, and internal mammary lymph nodes radiation. Several studies reporting improved heart sparing with new RT techniques in BC patients were searched. In addition to the RT modality, which definitely determines the feasibility of achieving lower doses for the organs at risk (OARs), better target coverage, dose conformity and homogeneity, and the patient's position, characteristics, and anatomy may also affect the evaluated RT dose to the whole heart and its substructures. Modern BC RT techniques seem to enable the administration of lower doses to the OARs without compromising on the target coverage. The analysis of several anatomical parameters and the assessment of cardiac biomarkers potentiate the protective effect of these new irradiation modalities, providing a holistic approach to the radiation-associated risks of cardiac disease for BC patients. Despite technological advances, an inevitable cardiac radiation risk still exists, while adverse cardiac events may be observed even many years after RT. Studies with longer follow-ups are required in order to determine the effectiveness of modern breast RT techniques.

Early effect of contemporary radiotherapy protocol on myocardium in patients with breast cancer assessed with cardiac magnetic resonance

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): University Medical Centre Ljubljana Research Grant. Introduction Early cardiotoxicity of modern radiotherapy (RT) is not known. Purpose To study the early cardiotoxic effect of contemporary RT on myocardium with cardiac magnetic resonance (CMR) in patients with breast cancer (BC). Methods Patients with in-situ ductal carcinoma of the breast, scheduled for RT were included. All patients had undergone surgical tumorectomy. Exclusion criteria were prior systemic chemotherapy, prior RT or known cardiac disease. Patients were treated with 3-dimensional conformal RT or intensity-modulated RT, left-sided BC patients were also scheduled for deep inspiration breath hold protocol, if feasible. Patients underwent CMR imaging prior to RT and within 2 weeks after RT. Left and right ventricular volumes and ejection fraction, global native and postcontrast T1 values and T2 values, prior to and after completion of RT were analyzed. All patients provided written informed consent. Results A total of 40 female patients (mean age 55 ± 7 years) were included, 22 with left-sided BC. The mean radiation dose was 42 Gy. CMR results are presented in Table 1. Left-sided BC patients had statistically significant increase in global T2 values. There were no significant differences in other studied parameters. No patient developed pericardial effusion and no patient had presence of late gadolinium enhancement at both exams. Conclusion Modern RT of left-sided BC is associated with increased T2 values, most likely representing myocardial edema, early after completion of RT.

Changes in left ventricular strain and cardiac biomarkers in a six-year prospective follow-up after breast cancer radiotherapy

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Finnish public grant Aims Breast cancer radiotherapy (RT) can lead to slowly developing cardiac dysfunction and increased incidence of heart failure with preserved ejection fraction (HFpEF). In fact, the risk for HFpEF is shown to be 16-fold after chest radiotherapy. We aimed to study the changes in left ventricular strain six years after radiotherapy as well as changes in cardiac biomarkers during the follow-up. Methods Early left-sided breast cancer patients (n=31) were prospectively followed-up for six years after RT. Left ventricular strain analysis and pro-brain natriuretic peptide (proBNP) tests were performed at baseline, after RT and at three-year and six-year controls. In addition, cardiac magnetic resonance imaging (CMR) was performed at the six-year follow-up. The results were compared with cardiac RT doses. Results Global longitudinal strain (GLS) declined only modestly from baseline 17.9±4.1% to 17.6±2.7% at six-year control (p = 0.731) while apical regions showed significant decline from baseline 24.6±6.6% to 19.8±3.5% at six-year control (p&amp;lt;0.001). ProBNP increased from baseline 63.0 [37.0, 124.0] ng/l to 98.0 [50.0, 215.0] ng/l at six-year follow-up (p = 0.022). Patients with (n=14) and without (n=16) worsening of apical strain and increase in proBNP had maximal left ventricular radiation doses 46.9±4.8 Gy versus 40.1±12.9 Gy (p = 0.049), respectively. Lower values in CMR strain were concentrated in the apical regions with an association with regional RT doses. Each 1 Gy of regional radiation dose decreased local regional strain value in CMR by 0.356 % [95%CI; 0.244, 0.468] (p&amp;lt;0.001). Conclusions A significant increase in proBNP and a significant decrease in apical strain were observed after RT in six-year follow-up. A higher left ventricular maximal radiation dose was significantly associated with worsening in apical strain and proBNP. In addition, a worse regional strain values in CMR had a dose-dependent association with corresponding RT doses. These results indicate that even contemporary breast cancer RT induces progressive cardiac changes.

Comparative dosimetric and radiobiological assessment of left-sided whole breast and regional nodes with advanced radiotherapy techniques.

The aim of this study was to analyze the dosimetric and radiobiologic differences of the left-sided whole breast and regional nodes in intensity-modulated radiotherapy (IMRT), volume-modulated arc therapy (VMAT), and helical tomotherapy (HT). The IMRT, VMAT, and HT plans in this study were generated for thirty-five left-sided breast cancer patients after breast-conserving surgery (BCS). The planning target volume (PTV) included the whole breast and supraclavicular nodes. PTV coverage, homogeneity index (HI), conformity index (CI), dose to organs at risk (OARs), secondary cancer complication probability (SCCP), and excess absolute risk (EAR) were used to evaluate the plans. Compared to IMRT, the VMAT and HT plans resulted in higher PTV coverage and homogeneity. The VMAT and HT plans also delivered a lower mean dose to the ipsilateral lung (9.19±1.36 Gy, 9.48±1.17 Gy vs. 11.31±1.42 Gy) and heart (3.99±0.86 Gy, 4.48±0.62 Gy vs. 5.53±1.02 Gy) and reduced the V5Gy, V10Gy, V20Gy, V30Gy, and V40Gy of the ipsilateral lung and heart. The SCCP and EAR for the ipsilateral lung were reduced by 3.67%, 3.09% in VMAT, and 22.18%, 19.21% in HT, respectively. While were increased for the contralateral lung and breast. This study showed that VMAT plans provide a more homogeneous dose distribution to the PTV, minimizing exposure to ipsilateral structures and significantly reducing SCCP and EAR, and slightly increasing dose to contralateral structures. Overall, the VMAT plan can be considered a beneficial technique for BCS patients whose PTV includes the whole breast and regional nodes.

Dosimetric comparison of breath-hold and free-breathing techniques in left-sided breast cancer patients treated with proton pencil beam scanning

Dosimetric comparison of breath-hold and free-breathing techniques in left-sided breast cancer patients treated with proton pencil beam scanning