Left-sided Breast Cancer Research Articles

Relationship between the Patients’ Setup Errors with Dosimetric and Radiobiologic Parameters in Whole Breast Radiotherapy

Purpose: This study aimed to investigate the effect of the patients’ setup errors on dosimetric and radiobiologic parameters for left-sided Whole-Breast Irradiation (WBI) in three different radiotherapy techniques, including Intensity-Modulated Radiation Therapy (IMRT), Field-In-Field (FIF), and Conventional Wedge (CW).
 Materials and Methods: Computed Tomography (CT) images of 10 female patients with early-stage left-sided breast cancer were used to simulate different radiotherapy techniques (IMRT, FIF, and CW). The dosimetric parameters; Conformity Index (CI), Homogeneity Index (HI), the dose received by at least 95% (D95%) of Planning Tumor Volume (PTV), the volume of lung and heart that respectively received at least 20% (V20%) and 40% (V40%) of the prescribed dose, as well as, the radiobiologic parameters, including Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) were assessed for setup errors in patients. The setup errors were assessed by shifting the isocenters and gantry angles of the treatment plans.
 Results: The D95% of the PTV for an isocenter misplacement plan in the posterior direction decreased by 66.99 (IMRT), 71.86 (CW), and 68.25% (FIF). The TCP of the PTV was reduced by 26.66, 39.16, and 36.97% for IMRT, CW, and FIF techniques, respectively. Increasing gantry angle by a ±10 degree caused a 43%, 41%, and 41% decrease in the D95% of IMRT, FIF, and CW techniques, respectively. The TCP values decreased about 18% in all three techniques with a ±10 degree gantry angle shift; however, the NTCP values of the heart and lungs increased for all three methods. The CI and HI values had significantly more changes with increasing setup errors in the IMRT than in the two techniques.
 Conclusion: The radiobiologic parameters in IMRT were less sensitive to setup errors compared to FIF and CW techniques. The radiobiological parameters can help estimate the setup errors along with physical parameters during breast radiotherapy.

Cardiac toxic effect of radiation therapy in patients receiving adjuvant trastuzumab treatment, as examined by LVEF of echocardiography: an experimental research.

This study aimed to evaluate the cardiotoxic consequences of radiotherapy in breast cancer patients who underwent adjuvant trastuzumab treatment by echocardiographic left ventricular ejection fraction (LVEF) measurement. In this retrospective study patients treated with postoperative breast irradiation with adjuvant trastuzumab were examined in terms of LVEF. Eithy five patients with age of 31-76 referred to the radiotherapy department of 5 Azar Hospital of Gorgan, Iran between years 2013 and 2020 were analyzed. Patients were divided into two left sided and right sided breast groups. Patients are routinely assessed every 3 months by echocardiocraphgy. LVEF values was measured at intervals of 3, 6, and 12 months after treatment onset. On the left side, the average of LVEF immediately decreased after treatment, compared to before treatment (∆ LVEF= 0.021), which shows the impact of trastuzumab. The LVEF average 3 months after treatment onset showed a significant decrease (∆ LVEF= 0.043) indicating a synergistic effect of trastuzumab and radiotherapy. LVEF average 6 months and 1 year after treatment onset showed a decrease but not significant (∆ LVEF= 0.009 and 0.013, respectively).In the right breast LVEF average immediately 3 months after treatment showed a significant decrease (∆ LVEF= 0.011 and 0.057, respectively). Nevertheless, LVEF average does not show a significant decrease after 6 months and 1 year after treatment in the right side group (∆ LVEF= 0.0002 and 0.018, respectively). Our results showed LVEF changes within one year following treatment in left sided breast cancer was more than right side , but the difference was not significant ,which may be due to the short period of our study based on the protocol of our department. More changes in the left side must be due to placing of the heart in the path of radiation. The study showed that LVEF may be an indicative measure for assessing radiation and adjuvant treatment effects on cardiac function.

Evaluation of Cardiac Substructures Exposure of DIBH-3DCRT, FB-HT, and FB-3DCRT in Hypofractionated Radiotherapy for Left-Sided Breast Cancer after Breast-Conserving Surgery: An In Silico Planning Study

Left-sided breast cancer radiotherapy can lead to late cardiovascular complications, including ischemic events. To mitigate these risks, cardiac-sparing techniques such as deep-inspiration breath-hold (DIBH) and intensity-modulated radiotherapy (IMRT) have been developed. However, recent studies have shown that mean heart dose is not a sufficient dosimetric parameter for assessing cardiac exposure. In this study, we aimed to compare the radiation exposure to cardiac substructures for ten patients who underwent hypofractionated radiotherapy using DIBH three-dimensional conformal radiation therapy (3DCRT), free-breathing (FB)-3DCRT, and FB helical tomotherapy (HT). Dosimetric parameters of cardiac substructures were analyzed, and the results were statistically compared using the Wilcoxon signed-rank test. This study found a significant reduction in the dose to the heart, left anterior descending coronary artery, and ventricles with DIBH-3DCRT and FB-HT compared to FB-3DCRT. While DIBH-3DCRT was very effective in sparing the heart, in some cases, it provided little or no cardiac sparing. FB-HT can be an interesting treatment modality to reduce the dose to major coronary vessels and ventricles and may be of interest for patients with cardiovascular risks who do not benefit from or cannot perform DIBH. These findings highlight the importance of cardiac-sparing techniques for precise delivery of radiation therapy.

Impact of breath hold on regional nodal irradiation and heart volume in field in left breast cancer adjuvant irradiation.

Compared to the free-breathing technique, adjuvant left breast irradiation after breast-conserving surgery or mastectomy using the breath-hold method significantly reduces the heart mean dose, Left anterior descending artery, and ipsilateral lung doses. Movement with deep inspiration may also reduce heart volume in the field and regional node doses. Pre-radiotherapy planning CT was performed in the free-breathing, and breath-hold techniques using RPM, demographic information, clinicopathological data, heart volume in the field, heart mean dose, LAD mean dose, and regional nodal doses were calculated in both free breathing and DIBH. Fifty patients with left breast cancer receiving left breast adjuvant radiation were enrolled. There was no significant difference in axillary LN coverage between the two techniques, except for SCL maximum dose, Axilla I node maximum dose, and Axilla II minimum dose in favor of the breath hold technique. The mean age was 47.54years, 78% had GII IDC, 66% had positive LVSI results, and 74% of patients had T2. The breath hold strategy resulted in considerably decreased mean heart dose (p = 0.000), LAD dose (p = 0.000), ipsilateral lung mean dose (p = 0.012), and heart volume if the field (p = 0.013). The mean cardiac dosage and the dose of the LAD were significantly correlated (p = 0.000, R = 0.673). Heart volume in the field and heart mean dosage was not significantly correlated (p = 0.285, r = -0.108). When compared to free breathing scans, DIBH procedures result in considerably reduced dosage to the OAR and no appreciable changes in dose exposure to regional lymph node stations in patients with left-sided breast cancer.

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.

Deep inspiration breath hold: dosimetric benefits to decrease cardiac dose during postoperative radiation therapy for breast cancer patients.

Postoperative radiation therapy (RT) is the standard treatment for almost all patients diagnosed with breast cancer. Even with modern RT techniques, parts of the heart may still receive higher doses than those recommended by clinically validated dose limit restrictions, especially when the left breast is irradiated. Deep inspiration breath hold (DIBH) may reduce irradiated cardiac volume compared to free breathing (FB) treatment. This study aimed to evaluate the dosimetric impact on the heart and left anterior descending coronary artery (LAD) in FB and DIBH RT planning in patients with left breast cancer. A retrospective cohort study of women diagnosed with left-sided breast cancer submitted to breast surgery followed by postoperative RT from 2015 to 2019. All patients were planned with FB and DIBH and hypofractionated dose prescription (40.05 Gy in 15 fractions). 68 patients were included in the study. For the coverage of the planned target volume evaluation [planning target volume (PTV) eval] there was no significant difference between the DIBH versus FB planning. For the heart and LAD parameters, all constraints evaluated favored DIBH planning, with statistical significance. Regarding the heart, median V16.8 Gy was 2.56% in FB vs. 0% in DIBH (p < 0.001); median V8.8 Gy was 3.47% in FB vs. 0% in DIBH (p < 0.001) and the median of mean heart dose was 1.97 Gy in FB vs. 0.92 Gy in DIBH (p < 0.001). For the LAD constraints D2% < 42 Gy, the median dose was 34.87 Gy in FB versus 5.8 Gy in DIBH (p < 0.001); V16.8 Gy < 10%, the median was 15.87% in FB versus 0% in DIBH (p < 0.001) and the median of mean LAD dose was 8.13Gy in FB versus 2.92Gy in DIBH (p < 0.001). The DIBH technique has consistently demonstrated a significant dose reduction in the heart and LAD in all evaluated constraints, while keeping the same dose coverage in the PTV eval.

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.

Radiotherapy-induced changes in right ventricular function in patients with early-stage breast cancer

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Finnish state research funding for university-level health research Background In breast cancer patient’s adjuvant RT nearly doubles cardiac mortality, and in some subgroups long-term cardiovascular mortality exceeds cancer mortality. The effects of RT on left ventricle are well established, but studies concerning right ventricular (RV) changes are sparse. Methods The study population consisted of 31 patients with early-stage left-sided breast cancer who had undergone adjuvant therapy using modern RT delivery techniques. Echocardiographic examinations including right ventricular (RV) strain analysis were performed prior to the RT, immediately after, as well as three and six years after the RT. In addition, the patients underwent cardiac magnetic resonance (CRM) imaging at six-year control. Results The mean RT dose to the RV free wall was 5.75±2.49 Gy. In echocardiography, basal early diastolic strain rate increased from 1.8±0.8 1/s to 2.3±0.9 1/s (p = 0.045), and the ratio of tricuspid inflow e and a-waves declined from 1.3±0.2 to 1.1±3.0 (p = 0.035), but there were no changes in global or regional strain or strain values in the six-year follow-up. In addition, In CMR imaging, the global circumferential strain values were associated with RV free wall RT dose (p = 0.005) with each mean Gy inducing 0.395% reduction in the circumferential strain [95% CI; −0.658, −0.120] whereas longitudinal strain was not associated with the RT dose. Conclusions Modern conformal breast cancer RT did not influence RV systolic function or result in clinically meaningful cardiac sequelae during six-year follow-up. Minor changes in RV diastolic function and the association between circumferential strain in CRM and the RT dose indicate that these parameters might be more sensitive in detecting RT-induced 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.

Comparison of 3D-conformal and intensity-modulated radiation therapy for left-sided breast cancer

Background: We compared 3D-conformal radiation therapy (3D-CRT) and intensity-modulated radiation therapy (IMRT) planning for left-sided post-mastectomy patients. Aim: To compare the dose coverage of the planning target volume (PTV) and dose delivered to organs at risk (OAR) of 3D-CRT and IMRT plans. Setting: Department of Oncology, central South Africa. Methods: Twenty-six archived CT scans of patients with left-sided breast cancer were included. The 3D-CRT and IMRT plans were designed for each patient and compared using the Monaco © planning system (version 5.11.02). Statistical analysis was performed for PTV coverage (V 95% , V 98% , V 105% ) and radiation doses to the heart, ipsilateral lung, combined lungs, contralateral breast, and oesophagus. Results: The V 98% and V 105% target volume dose coverage for the 3D-CRT plans were 67.07% and 0.21%, respectively, compared to 92.32% and 1.10% of the IMRT plans. However, the IMRT plans’ mean volume of PTV, receiving 95% of the prescribed dose (PD), was 7.68% compared to the 3D-CRT’s 32.93%. The IMRT plans resulted in a V 22 Gy &lt; 10% for the heart, with a value of 4.15%. The V 18.87 Gy &lt; 45% values for the ipsilateral and combined lungs were 28.09% and 13.70%, respectively. The 3D-CRT plans showed a lower dose to the oesophagus (5.07 Gy) and contralateral breast (V 5 Gy &lt; 15% = 3.51%). Conclusion: It was shown that 3D-CRT and IMRT treatment planning can effectively achieve clinical goals for post-mastectomy left-sided breast cancer radiotherapy. Contribution: The findings underscore the continuing relevance of 3D-CRT planning in oncology for optimal PTV dose coverage and low OAR dose.

Incidental Axillary Dose of Tomotherapy in Hypofractionated Whole Breast Radiotherapy for Early Breast Cancer: A Dosimetrical Analysis.

Background and Objectives: Intensity-modulated radiation therapy (IMRT) is becoming a more common method of performing whole breast irradiation (WBI) for early breast cancer. This study aimed to examine the incidental dose to the axillary region using tomotherapy, a unique form of IMRT. Patients and Methods: This study included 30 patients with early-stage breast cancer who underwent adjuvant WBI using TomoDirect IMRT. A hypofractionation scheme of 42.4 Gy delivered in 16 fractions was prescribed. The plan comprised of two parallel-opposed beams, along with two additional beams positioned anteriorly at gantry angles of 20° and 40° from the medial beam. The incidental dose received at axillary levels I, II, and III was evaluated using several dose-volume parameters. Results: The study participants had a median age of 51 years, and 60% had left-sided breast cancer. The mean dose of the axilla for levels I, II, and III were 15.5 ± 4.8 Gy, 14.9 ± 4.2 Gy, and 1.5 ± 1.6 Gy, respectively. Adequate coverage of the axilla, defined as V95%[%], was achieved for 4.7 ± 3.9%, 4.8 ± 3.7%, and 0 ± 0% for levels I, II, and III, respectively. The results were compared with those of previously published studies, and the axillary mean dose and V95%[%] of TomoDirect IMRT were low, comparable to other IMRT techniques, and lower than those of traditional tangential therapy. Conclusions: While incidental axillary radiation during WBI has been proposed to assist in regional disease control, the TomoDirect plan was demonstrated to decrease this dose, and a hypofractionation scheme would further lower its biological effectiveness. Future clinical studies should incorporate dosimetrical analysis of incidental axillary dose, in order to facilitate hypofractionated IMRT planning with risk-adjusted axilla coverage in early breast cancer.

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

A Potential Pitfall and Clinical Solutions in Surface-Guided Deep Inspiration Breath Hold Radiation Therapy for Left-Sided Breast Cancer

Deep inspiration breath hold (DIBH) is an effective technique to spare the heart in treating left-sided breast cancer. Surface-guided radiation therapy (SGRT) is increasingly applied in DIBH setup and motion monitoring. Patient-specific breathing behavior, either thoracically driven or abdominally driven (A-DIBH), should be unaltered, online identified, and monitored accordingly to ensure reproducible heart-sparing treatment. Sixty patients with left-sided breast cancer treated with SGRT were analyzed: 20 A-DIBH patients with vertical chest elevation (VCE ≤ 5 mm) were prospectively identified, and 40 control patients were retrospectively and randomly selected for comparison. At simulation, both free-breathing (FB) and DIBH computed tomography (CT) were acquired, guided by a motion surrogate placed around the xiphoid process. For SGRT treatment setups, the region of interest (ROI) was defined on the CT chest surface, and the surrogate-based setup was a backup. For all 60 patients, the VCE was measured as the average of the FB-to-DIBH elevations at the breast and xiphoid process, together with abdominal elevation. In the 40-patient control group, A-DIBH patients (VCE ≤ 5 mm) were identified. Of the 20 A-DIBH patients, 10 were treated with volumetric modulated arc therapy plans, and 10 patients were treated with tangent plans. Clinical DIBH plans were recalculated on FB CT to compare maximum dose (DMax), 5% of the maximum dose (D5%), mean dose (DMean), and V30Gy, V20Gy, and V5Gy of the heart and lungs and their significance. In the 20 A-DIBH patients, VCE=3 ± 2 mm, surrogate motion (9 ± 6 mm), and abdomen motion of 14 ± 5 mm are found. Heart dose reduction from FB to DIBH is significant (P < .01): ∆DMax=-8.4 ± 9.8 Gy, ∆D5%=-2.4 ± 4.4 Gy, and ∆DMean=-0.6 ± 0.9 Gy. Six out of 40 control patients (15%) are found to have VCE ≤ 5 mm. A-DIBH (VCE ≤ 5 mm) patient population is significant (15%), and they should be identified in the SGRT workflow and monitored accordingly. A new abdominal ROI or an abdominal surrogate should be used instead of the conventional chest-only ROI. Patient-specific DIBH should be preserved for higher reproducibility to ensure heart sparing.

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

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

Radiation-induced circulating microRNAs linked to echocardiography parameters after radiotherapy.

Patients treated with radiotherapy to the chest region are at risk of cardiac sequelae, however, identification of those with greatest risk of complications remains difficult. Here, we sought to determine whether short-term changes in circulating miRNA expression are related to measures of cardiac dysfunction in follow-up. Two parallel patient cohorts were enrolled and followed up for 3 years after completion of RT to treat left-sided breast cancer. In the primary group (N=28) we used a a panel of 752 miRNAs to identify miRNAs associated with radiation and cardiac indices at follow up. In the second, independent cohort (N=56) we validated those candidate miRNAs with a targeted qPCR panel. In both cohorts. serum samples were collected before RT, 24h after the last dose and 1 month after RT; cardiac echocardiography was performed 2.5-3 year after RT. Seven miRNAs in the primary group showed marked changes in serum miRNAs immediately after RT compared to baseline and associations with cardiopulmonary dose-volume histogram metrics. Among those miRNAs: miR-15b-5p, miR-22-3p, miR-424-5p and miR-451a were confirmed to show significant decrease of expression 24 hours post-RT in the validation cohort. Moreover, miR-29c, miR-451 and miR-424 were correlated with the end-diastolic diameter of the left ventricle, which was also confirmed in multivariable analysis adjusting for RT-associated factors. We identified a subset of circulating miRNAs predictive for cardiac function impairment in patients treated for left-sided breast cancer, although longer clinical observation could determine if these can be used to predict major clinical endpoints.

PET/MRI Assessment of Acute Cardiac Inflammation 1 Month After Left-Sided Breast Cancer Radiation Therapy.

Our purpose was to investigate the utility of 18F-FDG PET/MRI and serial blood work to detect early inflammatory responses and cardiac functionality changes at 1 mo after radiation therapy (RT) in patients with left-sided breast cancer. Methods: Fifteen left-sided breast cancer patients who enrolled in the RICT-BREAST study underwent cardiac PET/MRI at baseline and 1 mo after standard RT. Eleven patients received deep-inspiration breath-hold RT, whereas the others received free-breathing RT. A list-mode 18F-FDG PET scan with glucose suppression was acquired. Myocardial inflammation was quantified by the change in 18F-FDG SUVmean (based on body weight) and analyzed on the basis of the myocardial tissue associated with the left anterior descending, left circumflex, or right coronary artery territories. MRI assessments, including left ventricular functional and extracellular volumes (ECVs), were extracted from T1 (before and during a constant infusion of gadolinium) and cine images, respectively, acquired simultaneously during the PET acquisition. Cardiac injury and inflammation biomarker measurements of high-sensitivity troponin T, high-sensitivity C-reactive protein, and erythrocyte sedimentation rate were measured at the 1-mo follow-up and compared with preirradiation values. Results: At the 1-mo follow-up, a significant increase (10%) in myocardial SUVmean in left anterior descending segments (P = 0.04) and ECVs in slices at the apex (6%) and base (5%) was detected (P ≤ 0.02). Further, a significant reduction in left ventricular stroke volume (-7%) was seen (P < 0.02). No significant changes in any circulating biomarkers were seen at follow-up. Conclusion: Myocardial 18F-FDG uptake and functional MRI, including stroke volume and ECVs, were sensitive to changes at 1 mo after breast cancer RT, with findings suggesting an acute cardiac inflammatory response to RT.

Investigation of electrocardiography and echocardiography changes after adjuvant radiation therapy of left-sided breast cancer

IntroductionThe primary objective of radiation therapy (RT) is to deliver lethal radiation doses to abnormal cancer cells so that healthy cells are exposed to minimal radiation. In the present study, changes in electrocardiography (ECG) and echocardiography(ECHO) following adjuvant RT were investigated in patients with left-sided breast cancer. Materials and methods30 patients with left-sided breast cancer who had previously undergone breast-conserving surgery or mastectomy underwent RT after completing chemotherapy from February 2019 to January 2020. ECG and ECHO tests were performed before RT, immediately following RT, and three months after RT. Dose-volume parameters of the heart and its substructures as an organ at risk were analyzed. ResultsThe mean heart dose (±SD) for all patients was 7.51 ± 2.42 Gy. T-wave inversion was observed 3 months after RT in 47% of patients. T-wave decline was associated with mean heart radiation dose (β = 0.605, p-value = 0.005). The present study showed that the left ventricular volume receiving the 5 Gy (LV-V5) parameter was associated with a reduction in ST segment duration (p-value = 0.027) as well as with an increase in left ventricular systolic diameter (LVESD, mm) (P-value = 0.027). ConclusionRT-induced ECG and ECHO changes are frequent in patients with left breast cancer. LVEF and Twave abnormalities were observed after RT in our patients. ECG and ECHO modalities can be used to monitor the cardiac function after RT in patients with left-sided breast cancer.

Advancing Precision in Post-mastectomy Chest Wall Radiotherapy: A Comparative Dosimetric Analysis of Volumetric-Modulated Arc Therapy (VMAT) and Intensity-Modulated Radiotherapy (IMRT) Based on Institutional Experience.

Post-mastectomy radiation therapy (PMRT) is an important component in the management of breast cancer patients who have undergone mastectomy. Intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) are two popular methods of delivering PMRT. With IMRT, high radiation doses are directed at the tumor, while exposure to healthy tissue is kept to a minimum. VMAT, on the other hand, is a more advanced version of IMRT that allows for faster radiation dose delivery while maintaining precision. The complexity of the VMAT treatment planning and delivery process, on the other hand, may increase the risk of technical errors, which can reduce treatment effectiveness. Studies have compared VMAT and IMRT in PMRT for breast cancer patients, but most have found no significant differences in treatment outcomes between the two methods. Individual patient factors such as treatment goals, available resources, and other characteristics may influence the choice between the two techniques. This prospective observational study aimed to compare the dosimetry of two cutting-edge modern radiotherapy techniques for post-mastectomy breast cancer patients receiving hypofractionated doses. For 58 patients with breast cancer, 116 plans for radiotherapy treatment were generated by both VMAT and IMRT. To maintain the uniformity of contouring, every CT image was contoured by the same physician, and Radiotherapy Oncology Group (RTOG) contouring guidelines were strictly followed during contouring. Both techniques had comparable target volume coverage, but VMAT produced a significantly better conformity index than IMRT for both the left (0.71 vs. 0.65) and right (0.72 vs. 0.66) breasts (p-value < 0.05). VMAT plans had significantly higher low-dose spillage to the ipsilateral lung (V5Gy and V10Gy) but significantly lower high-dose spillage (V20Gy, V30Gy, and V40Gy) than IMRT plans (p-value < 0.05). Dmax and Dmean for the ipsilateral lung were comparable for both techniques. When compared to alternative treatment approaches, IMRT treatment plans were found to be more effective in minimizing radiation exposure to the heart for all patients with right-sided breast cancer, resulting in considerably lower levels of Dmean, V5Gy, V10Gy, V20Gy, and V35Gy. Plans for VMAT treatment were found to be significantly superior to left-side chest wall radiotherapy in terms of lower exposure to the heart for higher doses. IMRT plans, on the other hand, were successful in dramatically lowering the levels of Dmax that reached the spinal cord for both right- and left-sided breast cancers. Apart from similar planning target volume (PTV) coverage to IMRT plans, VMAT produced significantly better conformity. VMAT plans have more low-dose spillage to normal tissues, while IMRT plans spare various organs at risk significantly better at lower doses in both right and left-sided breast cancer. VMAT was found to be better at sparing the heart (in left-sided breast cancer only) and ipsilateral lung at a high dose range. The best radiotherapy approach for breast cancer should be established on an individual basis, taking into account tumor laterality and the risk-benefit ratio.