To compare dosimetric outcomes between Free Breath (FB) and Deep Inspiration Breath Hold (DIBH) across different radiotherapy modalities, establish patient selection criteria for DIBH, and optimizing the setup margin (SM) in left breast cancer treatment. 26 patients with left breast cancer were studied at CRO, Aviano in Italy. FB and DIBH simulations were done using CT with a real-time position management system. 3DCRT and IMRT plans were prepared for both simulations of each patient. The setup margin was measured by Van Herk's formula and compared with residual uncertainties. The dose coverage of PTV and spare OARs were better with DIBH. The distance of more than 1.6 cm between (Left Anterior Descending artery) LAD and PTV was no significantly different for FB and DIBH. The setup margin by Van Herk's formula was calculated as 0.9 cm for DIBH_IMRT. The average duration of DIBH per respiration was 19 ± 4 s. So, holding one breath at least 19 s would be the criteria for choosing a patient to apply DIBH. DIBH enhances PTV dose coverage and OAR sparing in both 3DCRT and IMRT. When the distance between the LAD and PTV exceeds 1.6 cm, the application of DIBH depends on the availability of a LINAC with RPM and the patient's breathholding ability.

Recent studies have shown that cardiac substructures and particularly left anterior descending artery (LAD) dose strongly correlates with the incidence of late adverse cardiac events. We evaluated whether greater cardiac and, importantly, LAD dose sparing could be achieved using a newly introduced closed bore (O-ring gantry) linac with a double-stacked multileaf collimator (Varian Ethos) relative to conventional linacs.

Twenty patients with locally advanced non-small cell lung cancer previously treated with definitive chemoradiotherapy were retrospectively evaluated. Volumetric modulated arc therapy plans were retrospectively generated for the Ethos system using optimization criteria focused on reducing overall heart and LAD doses (Heart_Ethos). Plans were also reoptimized using the same optimization criteria on a conventional C-arm linac (Heart_TB). Investigational plans were compared with the original plans and with each other using standard dose-volume histogram metrics such as percentage (V) volume receiving a specific dose (x) in Gy (Vx) or mean dose (Dmean) in Gy.

Statistically significant decreases existed between the Heart_Ethos and original plans for mean heart dose (11.3 vs 14.8 Gy; P < .001) and V5, V30, and V50 (63.6% vs 75.2%; P < .001, 7.1% vs 12.3%; P < .001, 2.1% vs 2.9%; P = .03, respectively) and also for LAD mean dose (4.8 Gy vs 12.0 Gy [P < .001]) and V15 (4.9% vs 21.5%; P < .001). Compared with Heart_TB, Heart_Ethos plans had significantly less mean heart dose (11.6 vs 12.2 Gy; P = .006), and less heart V5 (64.4% vs 67.2%; P = .049) and V30 (7.7% vs 8.8%; P = .03), whereas other parameters were not significant. Optimal target coverage and other organs at risk constraints were maintained for all generated plans.

Heart_Ethos plans showed significant reduction in cardiac and LAD doses in comparison to the original plans while maintaining target and organ at risk goals. Our findings suggest that Ethos technology has the potential for better cardiac toxicity safety because Heart_Ethos plans were still able to reduce cardiac dose compared with Heart_TB plans.

Exposure to diagnostic and therapeutic radiation introduces risks for development of diseases later in life by causing DNA damage in cells. Currently, there is no clinical method for determining exposure risk caused by radiation toxicity to DNA. Cell-free DNA (cfDNA), a marker of DNA damage, is currently used to assess risk for long-term effects following organ transplantation, surgery and inflammation. The goal of our proposed study is to develop cfDNA as an early biomarker for assessing risk for cardiovascular disease and cancer from radiation exposure so that strategies to mitigate the damaging effects of medical radiation can be assessed. Hearts from male and female WAG/RijCmcr rats (n = 6-10/group) were exposed to increasing doses of X-radiation (50 mGy and 3.5 Gy). Blood was collected prior to and after (15 minutes-96 hours) irradiation, and cell-free plasma was prepared. Primers and probes were designed for quantitative analysis of sequences of mitochondria (12S rRNA) and nuclear (Gapdh) cfDNA present in rat plasma using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Exposure of hearts to radiation increased nuclear and mitochondrial cfDNA in a dose-dependent manner. Three point five grays from X-radiation increase cfDNA for Gapdh in plasma after 1 hour with a 15.8-fold increase (P < 0.001) after 6 hours. The earliest time nuclear and mitochondrial cfDNA increases were detected in plasma was at 60 minutes following exposure to 3.5 Gy. cfDNA has potential to advance as a biomarker of exposure to medical doses of radiation in patients.

Adjuvant breast radiotherapy has been associated with cardiac toxicity due to older 2D and 3D techniques, with a linear relationship between mean heart dose (MHD) and ischemic cardiac events. Cardiac dose distribution differs with modern techniques like intensity-modulated radiotherapy (IMRT), potentially affecting this relationship. This study evaluates long-term cardiac toxicity in breast cancer patients treated with tomotherapy to reassess 3D-derived dose constraints. Breast cancer patients treated with tomotherapy at Institut Curie from August 2010 to December 2015 were included. Patients had undergone breast-conserving surgery or mastectomy, with some receiving chemotherapy or trastuzumab. Tomotherapy was used for anatomically challenging cases. The primary endpoint was cardiac toxicity correlated with MHD; secondary endpoints were overall and disease-specific survival. Statistical analyses included logistic regression and Cox models. Among 179 patients, the median MHD was 7.04 Gy, with 95.6% having an MHD above 5 Gy. Sixty-six patients had cardiovascular risk factors, and 28.5% were obese. Over a median follow-up of 9.1 years, eight patients (4.5%) experienced cardiovascular events-all with pre-existing risks or obesity. No significant correlation was found between MHD and major coronary events (p = 0.607) or heart failure (p = 0.800). Cardiac mortality was absent, and 10-year overall and disease-specific survival were 88.0% and 94.3%, respectively. Cardiac events in patients treated with tomotherapy were rare and driven by pre-existing risk factors. The linear MHD-toxicity relationship observed in 3D radiotherapy may not apply to IMRT, potentially leading to overestimated risks. Long-term studies are needed to refine IMRT dose constraints.

Radiation-induced heart disease (RIHD) is a prevalent cardiovascular complication of radiation therapy, with coronary heart disease being the most common manifestation. Clinical presentations of RIHD vary and may include conduction abnormalities, ischemic heart disease, cardiomyopathy, heart failure, and valvular damage. Even low doses of radiation significantly increase the risk of cardiovascular disease, often associated with severe stenosis detected via angiography. Radiation-induced damage to the cardiac endothelium triggers inflammatory responses and oxidative stress, which contribute to the progression of atherosclerosis. This study explores how radiation activates multiple signaling pathways through the generation of reactive oxygen species, resulting in vascular endothelial damage, cellular senescence, inflammatory responses, and DNA damage. It further examines the impact of radiation on vascular integrity and tight junction proteins, leading to increased vascular permeability and infiltration by inflammatory cells. From a clinical perspective, we emphasize the challenges posed by the coexistence of tumors in many patients with RIHD, as tumors complicate the microenvironment and may have mutually reinforcing interactions with radiation-induced damage. We also discuss various therapeutic strategies, including novel approaches targeting cellular senescence and immune responses, with a focus on the potential use of navitoclax and IL-6 (interleukin-6) inhibitors to prevent irreversible cardiomyocyte fibrosis and ongoing vascular damage. In conclusion, RIHD is a multifaceted disease involving complex biological processes and signaling pathways. Early intervention and targeted therapies are crucial for improving patient outcomes. Future research should prioritize uncovering the molecular mechanisms of RIHD and developing more effective therapeutic strategies.

To update the ASCO evidence-based recommendations on the use of sentinel lymph node biopsy (SLNB) in patients with early-stage breast cancer treated with initial surgery.

ASCO convened an Expert Panel to develop updated recommendations based on a systematic literature review (January 2016-May 2024).

Eleven randomized clinical trials (14 publications), eight meta-analyses and/or systematic reviews, and one prospective cohort study met the inclusion criteria for this systematic review. Expert Panel members used available evidence and informal consensus to develop practice recommendations.

Clinicians should not recommend routine SLNB in select patients who are postmenopausal and ≥50 years of age and with negative findings on preoperative axillary ultrasound for grade 1-2, small (≤2 cm), hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer and who undergo breast-conserving therapy. Clinicians may offer postmastectomy radiation (RT) with regional nodal irradiation (RNI) and omit axillary lymph node dissection (ALND) in patients with clinically node-negative invasive breast cancer ≤5 cm who receive mastectomy and have one to two positive sentinel nodes. Clinicians may offer SLNB in patients who have cT3-T4c or multicentric tumors (clinically node-negative) or ductal carcinoma in situ treated with mastectomy, and in patients who are obese, male, or pregnant, or who have had prior breast or axillary surgery. Clinicians should not recommend ALND for patients with early-stage breast cancer who do not have nodal metastases, and clinicians should not recommend ALND for patients with early-stage breast cancer who have one or two sentinel lymph node metastases and will receive breast-conserving surgery and whole-breast RT with or without RNI.Additional information is available at www.asco.org/breast-cancer-guidelines.This guideline has been endorsed by the American Society for Radiation Oncology (ASTRO).

The goal of this work is to compare the Varian TrueBeam plan quality and delivery verification with two Halcyon plans in order to give a Varian Halcyon planning solution for left-sided breast postmastectomy radiotherapy (PMRT). Twenty-five patients who previously received left-sided breast postmastectomy intensity-modulated radiotherapy (IMRT) on TrueBeam were retrospectively selected and replanned using Halcyon. The planning target volume (PTV) included the chest wall, the supra/infra-clavicular region, and the internal mammary region, with a prescribed dose of 50 Gy in 25 fractions (2 Gy/F). For each patient, a Halcyon IMRT (HA-IMRT) plan and a Halcyon volumetric-modulated arc treatment (HA-VMAT) plan were created in addition to the initial TrueBeam fixed-jaws IMRT (TB-IMRT) plan. The conformity index (CI) and homogeneity index (HI) of the PTVs, the dose of organs at risk (OARs), the delivery MUs and time, and the verification passing rate were calculated and compared. Statistical significance was determined with a significance level of 0.05 using the Wilcoxon signed-rank test. HA-IMRT and TB-IMRT made generally clinical equivalence and have tiny differences for target coverage and OAR sparing. HA-IMRT lowered the V10, V20, V30, and Dmean of the ipsilateral lung, the V5, V10, V20, V30, and Dmean of the heart compared to TB-IMRT (p < 0.05). On the other hand, it increased V5 of the ipsilateral lung, Dmean of the contralateral lung, V10 of the contralateral breast, left humeral head, and thyroid, and HI of the target (p < 0.05). No significant differences were found in CI, V5 and V10 of the contralateral lung, V5 and Dmean of the contralateral breast, V30 and Dmax of thyroid, Dmean and Dmax of esophagus, or Dmax of spinal cord (p > 0.05). HA-VMAT showed a better CI but increased most OAR metrics mentioned above than TB-IMRT and/or HA-IMRT (p < 0.05). Both HA-IMRT and HA-VMAT decreased delivery time compared to TB-IMRT (2.96 ± 0.61 min, 0.77 ± 0.11 min, and 3.52 ± 0.92 min, respectively, p < 0.05). The mean gamma passing rates of HA-IMRT and HA-VMAT were also significantly raised compared to TB-IMRT.

Cancer therapy-related cardiovascular toxicity (CTR-CVT) poses a major challenge in managing cancer patients, contributing significantly to morbidity and mortality among survivors. CTR-CVT includes various cardiovascular issues, such as cardiomyopathy, myocardial ischemia, arrhythmias, and vascular dysfunction, which significantly impact patient prognosis and quality of life. Metabolic reprogramming, characterized by disruptions in glucose, lipid, and amino acid metabolism, represents a shared pathophysiological feature of cancer and cardiovascular diseases; however, the precise mechanisms underlying CTR-CVT remain inadequately understood. In recent years, strategies targeting metabolic pathways have shown promise in reducing cardiovascular risks while optimizing cancer treatment efficacy. This review systematically summarizes metabolic reprogramming characteristics in both cancer and cardiovascular diseases, analyzes how anticancer therapies induce cardiovascular toxicity through metabolic alterations, and explores emerging therapeutic strategies targeting metabolic dysregulation. By integrating current research advancements, this review aims to enhance the understanding of CTR-CVT and provide groundwork for the development of safer and more effective cancer approaches.

We assess the relationship between radiation dose to the heart and cardiac disease within the context of modern radiotherapy techniques of 3-dimensional and intensity-modulated radiotherapy (IMRT). The KROG 15-03 study was a multicenter phase III trial involving 693 breast cancer patients who underwent breast-conserving surgery (BCS). Patients were randomly assigned to receive either IMRT or 3D-CRT following BCS. Major cardiac event (MCE), defined as the occurrence of angina pectoris or myocardial infarction requiring coronary angiography, and admission for cardiac arrhythmia related to the irradiation of the heart. The primary outcome of the study was to investigate the incidence of MCE and factors associated with MCEs. At a median follow-up of 6.5 years, the incidence of MCEs at 6.5 years was 1.8%. The mean heart dose (MHD) for the entire cohort of 647 patients was 2.1 (±2.3) Gy. The cumulative incidence of MCEs at 6.5 years was 1.1% for the subgroup of MHD <2.9 Gy and 3.3% for the subgroup of MHD >2.9 Gy (p = 0.010), and 0.9% for the subgroup of age ≤55 years and 3.3% for the subgroup of age >55 years (p = 0.006), respectively. Multivariate analyses confirmed that MHD (p = 0.044; hazard ratio [HR], 1.21 per 1 Gy; 95% confidence interval [CI], 1.09-1.46) and age (p = 0.034; HR, 1.07 per 1 year; 95% CI, 1.03-1.14) were significant factors of MCEs. The incidence of MCE increased by 21% per 1-Gy increase in MHD within 6.5 years after radiotherapy.

To analyze the effect of jaw width in jaw tracking mode on the dose of radiotherapy partial arc VMAT (P-VMAT) for patients undergoing left breast-conserving surgery and to explore the best jaw width as the initial inverse optimization parameter. Twenty patients who underwent left breast-conserving surgery were randomly selected. Six groups of P-VMAT plans were designed (named Plan0, Plan0.3, Plan0.6, Plan0.9, Plan-0.3, and Plan-0.6). The width of the jaw of each plan was changed in 0.3 cm steps along the X direction (from - 0.6 to 0.9 cm) according to the beginning of the half beam (Plan0). The PTV coverage, conformity index (CI), homogeneity index (HI), monitor units (MU) and organs at risk (OARs) dose were evaluated by repeated measurement data analysis of variance between plan0 and the other plans. Additionally, the correlations between CI, HI, MU and OARs to change in jaw width were analyzed using Spearman's bivariate correlation analysis. The PTV dose distributions of Plan-0.3 and Plan-0.6, which have smaller jaw widths than those of Plan0, did not meet the clinical requirements. CI, HI and MU were correlated with jaw width (r = 0.554, -0.501, -0.641, p < 0.05, respectively). The V5, V10, V20, V40, Dmean and Dmax of the heart were correlated with jaw width (r = 0.288, 0.284, 0.191, -0.27, 0.186, -0.245, p < 0.05, respectively). The V2.5, V5, V10, V20, V40 and Dmean of the left lung (Lung-L) were correlated with jaw width (0.298, 0.421, 0.516, 0.391, -0.241, 0.356, p < 0.05, respectively). Among all the plans to ensure PTV target coverage, Plan0 had the lowest clinical indicators for the heart and Lung-L (p < 0.05, respectively). The internal boundary of the jaw set as 0 cm (Plan0) represents the optimal jaw width for the initial optimization of the plan design. This method is the simplest and most effective for radiotherapy treatment planning for breast-conserving surgery for breast cancer as well as allows ideal dose distribution.

Isolated nodal recurrence (INR) after localized breast cancer is rare, with an incidence of less than 1%. Curative management typically includes surgical resection, often with axillary lymph node dissection (ALND), followed by regional nodal radiotherapy. However, evidence-based guidelines remain limited due to the rarity of this clinical scenario. The aim of this study was to evaluate survival determinants and the acute and long-term toxicities associated with second-course regional nodal irradiation as part of curative strategies for INR after localized breast cancer.

This retrospective study included 11 patients with localized breast cancer who developed ipsilateral, nonmetastatic INR between 2003 and 2019. All patients were treated with curative intent, including regional nodal irradiation. Overall survival (OS), cancer-specific survival (CSS), metastasis-free survival (MFS), local control, and treatment toxicities were analyzed. Survival probabilities were calculated using the Kaplan-Meier method, and Cox regression was used to assess prognostic factors.

The 5‑year OS and CSS were 71.6%, while MFS was 62.3%. Inclusion of internal mammary chain (IMC) irradiation significantly improved OS, CSS, and MFS (p < 0.01). Triple-negative breast cancer (TNBC) INRs were associated with worse survival outcomes. Acute grade 2 toxicities included radiodermatitis (36.4%), and late grade 2 toxicities were limited to fibrosis (18.2%). No cardiac, pulmonary, or grade 3 or higher toxicities were reported.

This study highlights the favorable survival outcomes and safety profile of contemporary curative strategies for INRs following localized breast cancer, with a 5-year OS rate exceeding historical benchmarks. Internal mammary chain irradiation appears to improve survival without increased toxicity. However, the poor prognosis associated with TNBC INR underscores the need for effective systemic therapies. Prospective multicenter trials are essential to validate these findings and optimize treatment protocols.

Background: Prone breast radiotherapy has been shown to optimally spare the dose to the heart and lungs; we report on the heart and left anterior descending coronary artery (LAD) dosimetry and their implications for current care. Aims: (I) To measure the mean heart dose (MHD) and LAD mean and maximum doses (Dmean and Dmax) in patients with left-side breast cancer who have undergone hypo-fractionated whole breast radiotherapy (WBRT) with a concomitant boost to the post-operative cavity (40.50 Gy to the breast and 48 Gy to the cavity in 15 fractions) in the prone position; (II) to compare the dosimetry results to those reported in the literature for other techniques. Materials and Methods: In a consecutive series of 524 irradiated left-side breast cancer patients, heart and LAD dosimetry data were collected and correlated to breast volume and the volume of the radiation boost to the tumor cavity. A descriptive statistical analysis was performed to compare the same dosimetry data with those reported in the literature from supine techniques. To account for dosimetry differences in hypo-fractionation and conventional fractionated regimens (50-60 Gy in 25-30 fractions) reported in the literature, the cardiac doses were converted to the equivalent dose in 2 Gy fractions (EQD2). As previously reported, the prone setup protocol placed the medial edges of the tangential radiation fields at least 2.5 mm from the contoured LAD. Results: In all patients' plans, the target coverage was successfully achieved. The mean values (±SD) were as follows: MHD = 0.69 Gy (±0.19) (EQD2 0.35 Gy ± 0.1); LAD Dmean = 2.20 Gy (±0.68) (EQD2 1.18 Gy ± 0.35); LAD Dmax = 4.44 Gy (±1.82) (EQD2 2.55 Gy ± 0.97). The values were consistently lower compared with those achieved by the multiple supine techniques reported in the literature. Spearman's correlation analysis revealed a strong positive correlation between LAD and heart dosimetry variables. In contrast, no strong correlation was observed between the cardiac dose metrics and breast volume, boost volume, or their ratio index. A linear correlation was detected between LAD Dmean and LAD D2% (R2 0.64); LAD D2% and heart D2% (R2 0.60); LAD Dmax and heart D2% (R2 0.41). Conclusions: The prone position protocol minimizes heart and LAD exposure. This approach results in a dosimetry advantage when compared with more complex and expensive WBRT techniques in the supine position.

To evaluate the performance of the VitalHold module for automated Deep Inspiration Breath-Hold (DIBH) treatment on the Radixact platform, focusing on its dosimetric accuracy, responsiveness to respiratory motion and system latency.

A Delta4 Phantom+ system with customized 3D-printed breast add-ons was used to simulate a clinically relevant setup for DIBH. A treatment plan was created with 40 Gy in 15 fractions using TomoDirect. The Phantom was coupled with the HexaMotion motion platform to to simulate simple (tested with various amplitude, periods and gating thresholds) and complex respiratory patterns, including irregular breathing, patient-specific motion, and baseline shifts. Respiratory motion was analyzed, and dose distributions were measured using gamma analysis with varying criteria. System latency was evaluated following TG-147 guidelines.

The measured simple respiratory curve closely matched the simulated motion, with amplitude differences under 0.1 mm and cycle variations of 0.1 s. Gamma pass rates for 2-5 mm gating tolerances were ≥95 %, indicating high system accuracy. Complex motion scenarios showed average measured amplitude deviations below 0.1 mm. The system exhibited a mean latency of 4.3 ms.

The VitalHold module on the Radixact platform demonstrates strong potential for automated DIBH treatment, providing precise and reliable beam control across both simple and complex respiratory patterns and exhibiting minimal latency. This study supports the integration of automated breath-hold techniques in clinical practice.

Currently there is no widely used upfront selection method to determine whether patients are suitable for deep inspiration breath-hold (DIBH) in left-sided breast radiotherapy.

To establish an upfront patient selection strategy to improve the decision-making efficiency of DIBH and avoid extra computed tomography (CT) exposure to patients.

A total of 174 patients who underwent both free-breathing (FB) and DIBH scans were enrolled. A general principal component analysis model for DIBH-CT synthesis was trained and consists of principal component feature vectors extracted from paired FB-CT and DIBH-CT in training set. The coefficients of the vectors were optimized to minimize the difference between synthetic CT and breath-hold scout image of each patient in test set, leading to personalized DIBH-CT synthesis. An upfront patient selection strategy was established based on cardiac dose in synthetic DIBH-CT plan. The performance of DIBH-CT synthesis was analyzed in terms of geometric and dosimetric consistency between synthetic and scanned DIBH-CTs. The accuracy of the patient selection strategy was evaluated. Time assumption of the patient selection workflow was analyzed.

Synthetic DIBH-CTs had average Dice similarity coefficients of 0.84 for the heart and 0.91 for the lungs compared with scanned DIBH-CTs. Synthetic DIBH-CT plans revealed an average mean heart dose reduction of 1.46 Gy, which was not significantly different from 1.51 Gy in scanned DIBH-CT plans (p = 0.878). The patient selection strategy yielded the correct benefit results with accuracy of 86.7 %. The average time assumption for patient selection was 11.9 ± 3.6 min.

The proposed patient selection strategy can accurately identify patients benefiting from DIBH and provides a more efficient workflow for DIBH.

The cardiac and pulmonary dosimetric benefit of alternative positioning in isocentric lateral decubitus compared with dorsal decubitus during adjuvant breast irradiation has yet to be proven, in spite of the relative long-standing use of isocentric lateral decubitus.

Eight consecutive patients with an indication for adjuvant breast irradiation without boost or lymph node irradiation were scanned in both isocentric lateral and dorsal decubitus positions. For each patient, a plan delivering 40.05 Gy in 15 fractions in isocentric lateral decubitus and in dorsal decubitus using a field-in-field technique was calculated. Doses to the heart, to various cardiac substructures, and to the lungs were compared.

Mean dose to the heart, to various cardiac structures (left ventricle, left coronary, right coronary), to the homolateral lung, and to the contralateral lung were significantly lower in isocentric lateral decubitus than in dorsal decubitus. Average absolute mean dose reductions were -40 cGy for the heart, -27.5 cGy for the left ventricle, -56.5 cGy for the right coronary artery, -64.5 cGy for the left coronary artery, -45.5 cGy for the sinoatrial node, -74 cGy for the homolateral lung, and -4.5 cGy for the contralateral lung. For all organs at risk, median dose-volume histograms in isocentric lateral decubitus showed lower relative volumes than in dorsal decubitus.

Lateral decubitus positioning significantly reduces dose to the heart, to various cardiac substructures, to the homolateral lung, and to the contralateral lung, compared with dorsal decubitus. This technique is easily implemented and can be widely recommended to reduce heart and lung doses to a minimum.

Lateral decubitus positioning significantly reduces dose to the heart, to various cardiac substructures, to the homolateral lung, and to the contralateral lung, compared with dorsal decubitus. This technique is easily implemented and can be widely recommended to reduce heart and lung doses to a minimum.

This study used coronary computed tomography angiography (CCTA) in left breast cancer patients. It assessed real-time dose delivery of postmastectomy radiotherapy (PMRT) with internal lymph node irradiation (IMNIs) and normal tissue complications probability (NTCP) to the heart and subcardiac structures using tangential volumetric modulated arc therapy (T-VMAT). This research and its findings are critical in refining PMRT strategies to safeguard patient health and promote the overall efficacy of cancer management protocols. In this study, CCTA images from 16 patients were analyzed. These images were reconstructed at multiple phases (0%-90%) of the cardiac cycle for each patient. Substructures including the left ventricle (LV), right ventricle (RV), right atrium (RA), left atrium (LA), right coronary artery (RCA), and left anterior descending artery (LAD) were delineated using the RTOG 1106 OAR atlas guidelines. A rigid registration process aligned the CCTA images with planning chest CT scans. The heart's CT values were adjusted to ensure accuracy in electron density representation. The PTV was simulated, and a T-VMAT plan was created. The radiation fields were then applied to the 10 different cardiac phase images, and an accumulated plan was generated and compared with a conventional radiotherapy plan. Comparing the accumulated plan with the conventional plan, the absolute Dmean difference to the heart was 73.2 (cGy), and demonstrated a significant change of 14%. Among cardiac substructures, the largest differences in Dmean were observed in the LAD, RCA and LV-V25 with a variation of 387.5 cGy (22.5%), 195.8 cGy (34.7%) and 1.53% (52%), respectively. NTCP was slightly higher in the accumulated plan (0.44±1.57%) than in the conventional plan (0.17±0.47%). The results of this study underscore the critical role of real-time cardiac imaging in refining the delivery of PMRT with IMNIs. By leveraging CCTA and T-VMAT, we have achieved a more precise assessment of the cardiac dose, leading to a potential reduction in radiation-related cardiovascular risks without compromising cancer treatment efficacy. This research highlights the importance of integrating advanced imaging and radiation planning techniques to ensure the highest standards of patient care in the context of left breast cancer treatment.

Cardiotoxicity is a concern, especially in left breast cancer (BC) radiotherapy (RT), and accurate dosimetry is essential for minimizing cardiac exposure. This study evaluated the radiation exposure of cardiac substructures in node-positive and node-negative BC patients who underwent three-dimensional conformal therapy (3D-CRT) and compared the predictive accuracy of mean heart dose (MHD) and mean left ventricular dose (MLVD) in estimating dose distribution to cardiac substructures.

This study included 55 patients with left-sided breast cancer, comprising 39 with node-positive and 16 with node-negative disease. All underwent adjuvant whole-breast irradiation using 3D-CRT. The heart, ventricles, atria, right coronary (RC), left anterior descending coronary (LADCA), and left circumflex (LCx) arteries were contoured. Dosimetric distributions were evaluated, and Pearson's correlation and linear regression analyses were used to assess the relationship between cardiac substructures.

The distribution of doses to cardiac substructures was heterogeneous, with LADCA receiving the highest doses: 15.6 Gy in node-positive and 13.2 Gy in node-negative breast cancer patients. Linear regression analysis revealed a weak to moderate predictive ability of MHD/MLVD to predict doses received by the cardiac substructure in both groups, with MLVD demonstrating marginally better results. For node-positive patients, the analysis revealed an R² of 0.40 (p < 0.001) for the association between MHD and LADCA and an R² of 0.45 (p < 0.001) for MLVD and LADCA. In node-negative patients, the R² values were 0.27 (p < 0.001) for MHD versus LADCA and 0.30 (p < 0.03) for MLVD versus LADCA. Pearson's correlation analysis for node-positive patients indicated r = 0.63 (p < 0.001) for MHD versus LADCA and r = 0.67 (p < 0.001) for MLVD versus LADCA. For node-negative patients, the correlation coefficients were r = 0.52 (p < 0.001) for MHD versus LADCA and r = 0.54 (p < 0.001) for MLVD versus LADCA.

Radiation exposure to cardiac substructures during 3D-CRT for left breast cancer was heterogeneous, with the LADCA receiving the highest mean dose, followed by the LV. MLVD demonstrated superior predictive accuracy over mean heart dose (MHD) for estimating doses to critical substructures, particularly in node-positive patients.

In recent years, the continuous optimization of anti-tumor therapy has greatly improved the cancer-specific survival rate for patients with breast cancer (BC). The prevention and treatment of breast cancer-related heart diseases have become a new breakthrough in improving the long-term survival for BC patient. The cardiac damages caused by BC treatment are increasingly prominent among BC patients, of which ischemic heart disease (IHD) is the most prominent. Besides, the systemic inflammatory response activated by tumor microenvironment c an induce and exacerbate IHD and increase the risk of myocardial infarction (MI). Conversely, IHD can also exert detrimental effects on tumors. MI not only increases the risk of BC, but also induces specialized immune cell to BC and accelerates the progression of BC. Meanwhile, the treatment of IHD can also promote BC metastasis and transition to more aggressive phenotypes. Although BC and IHD are diseases of two independent systems, their crosstalk increases the difficulty of anti-cancer treatment and IHD management, which reduces the survival for both diseases. Therefore, this review mainly explores the mutual influence and underlying mechanisms between BC and IHD, aiming to provide insights for improving the long-term survival for patients with BC or IHD.

The purpose is to show the impact of patient coaching and home practice using the deep inspiration breath hold (DIBH) technique on radiation treatment set-up times and cardiac at-risk doses.

The study involved patients who received tangential field radiotherapy using the DIBH technique for treating left breast cancer. Patients were divided into two groups: the first group consisted of those who received coaching from an oncology nurse and were given an instruction sheet at least 1 week before the computed tomography (CT) simulation. The second group consisted of those who were only taught how to hold their breath by the radiation technician on the simulation day and without further education. During treatment, the patients were monitored using the Varian RPM™ respiratory gating system, and 2D kV orthogonal imaging was performed daily. The setup duration of each patient was noted and compared between treatment groups. For each patient, the dose-volume histograms (DVHs) of the heart, LAD (left anterior descending artery), were calculated and compared for both coached DIBH (cDIBH) and non-coached DIBH (ncDIBH).

Thirty-six coached and 28 non-coached patients were identified. Compared with ncDIBH, coached patients were older (55.5 versus 46.5, p = 0.003) and had a significantly higher BMI (body mass index) (29.95 versus 26.32 kg/m2, p = 0.006). Nevertheless, in more than half of the treatment fractions, the set-up duration was detected to be statistically longer in the ncDIBH group than in the cDIBH group. Additionally, the LAD max dose was significantly lower in the cDIBH group (36.5 versus 29.5, p = 0.02).

Coaching at least 1 week before the simulation with an instruction sheet decreased the set-up duration, and the cardiac LAD max dose should be further decreased by this method.

The field of cardio-oncology has expanded over the past 2 decades to address the ever-increasing issues related to cardiovascular disease in patients with cancer and survivors. There is increasing recognition that nearly all cancer treatments pose some short- or long-term risk for development of cardiovascular disease and that pediatric patients with cancer may be especially vulnerable to cardiovascular disease because of young age at treatment and expected long life span afterward. Anthracycline chemotherapy and chest-directed radiotherapy are the most well-studied cardiotoxic therapies, and dose reduction, use of cardioprotection for anthracyclines, and modern radiotherapy approaches have contributed to improved cardiovascular outcomes for survivors. Newer treatments such as small-molecule inhibitors, antibody-based cytotoxic therapy, and immunotherapy have expanded options for previously difficult-to-treat cancers but have also revealed new cardiotoxic profiles. Application of effective surveillance strategies in patients with cancer and survivors has been a focus of practitioners and researchers, whereas the prevention and treatment of extant cardiovascular disease is still developing. Incorporation of new strategies in an equitable manner and appropriate transition from pediatric to adult care will greatly influence long-term health-related outcomes in the growing population of childhood cancer survivors at risk for cardiovascular disease.

Cancer-treatment induced cardiovascular diseases are a concern in early breast cancer, especially when radiation is involved and systemic treatments may contribute. Our primary objective was to estimate the frequency of cardiac adverse events after early breast cancer treatment. We performed a systematic review on cardiac events after early breast cancer treatment, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, by searching PubMed, Scopus and Web of Science and cross-checking references from international guidelines on breast cancer treatment and cardio-oncology. Eighty-one studies were selected. Reporting of cardiac events and dose parameters was heterogeneous among studies due to the variability of the events being considered, follow-up duration and patient's age (most reported less than 5% with some as high as 34% at a maximum follow-up of 28 years). The most frequent are ischemic and valvular heart disease. Radiation modalities (hypofractionation, boost, partial or nodal irradiation) do not seem to change the risk of cardiac events. Anthracycline and aromatase inhibitors increase long-term cardiac risk, whereas anti-HER2-related effects are mostly transient. Myocardites with immunotherapy are rare (<1%) but follow-up is short. Other chemotherapy agents and poly(adenosine-diphosphate-ribose)-polymerase inhibitors have not been shown to increase cardiac risks which is reduced with more recent treatments, and increased by young age at diagnosis and previous cardiac risk factors. Advances in treatment seem to lower cardiac events. Prospective studies with exhaustive reporting of toxicity and radiotherapy features are warranted as well as the help of a cardio-oncologist to manage risk factors.

Standard therapy for breast cancer after breast-conserving surgery is radiation therapy (RT) plus hormone therapy (HT). For patients with a low-risk of recurrence, there is an interest in deescalating therapy.

A retrospective study was carried out for patients treated at the Swedish Cancer Institute from 2000 to 2015, aged 70 years or older, with pT1N0 or pT1NX estrogen receptor-positive and ERBB2-negative unifocal breast cancer without positive surgical margins, high nuclear grade, or lymphovascular invasion.

Patient numbers were sufficient to carry out analyses for RT + HT (n = 307) and RT alone (n = 148). The median follow-up was 9.6 years. There were no statistically significant differences in adjusted overall survival (OS), disease-specific death, progression-free survival (PFS), distant recurrence, and second primary cancers with RT monotherapy compared with RT + HT. Cumulative rates of all of these outcomes were <5%, even at 15 years of follow-up, regardless of treatment, greatly outweighed by the incidence of death from other causes in this elderly population. In matched analysis, we calculated a hazard ratio of 1.12 (95% CI, 0.82-1.53) for RT versus RT + HT for OS and a hazard ratio of 1.12 (95% CI, 0.82-1.53) for RT versus RT + HT for PFS.

Our data suggest that elderly, low-risk breast cancer patients have similarly high OS and PFS with low rates of local recurrence, distant recurrence, and death from breast cancer with much higher rates of death from competing causes, whether treated with RT or HT + RT. These patients are likely to die of other causes without disease recurrence, regardless of which of these treatments is used. Thus, they may benefit from the administration of more modern forms of breast irradiation without the need for adjuvant systemic hormone therapy. A detailed analysis of which clinical, pathologic, genomic, and comorbidity variables are needed to select these patients.

To conduct a systematic review of breast cancer radiotherapy studies reporting a comparison of proton beam therapy (PBT) in deep inspiration breath hold (DIBH) and in free breathing (FB).

Studies comparing DIBH and FB proton beam therapy plans, in the same patient, published between 2015 and 2023 were included. Doses to organs at risk were compared between DIBH and FB plans.

Nine papers were identified for inclusion, reporting on 97 patients in total. All plans were for left-sided treatment. Average weighted mean heart dose was 0.31 Gy for DIBH and 0.48 Gy for FB. Average weighted mean left lung dose was 5.27 Gy for DIBH and 4.80 Gy for FB. Average weighted mean near maximum/maximum left anterior descending artery dose was 6.49 Gy for DIBH and 8.74 Gy for FB.

Based on the current literature, it does not appear that DIBH offers a marked dosimetric benefit to most breast cancer patients treated with PBT. However, the benefits of combining PBT and DIBH for individual breast RT patients cannot be excluded.

Breast cancer is the most prevalent cancer in women worldwide; nevertheless, the prognosis is good, with a 5-year overall survival of 80-90%. Therefore, it becomes crucial to strive for high quality of life after cure by minimizing treatment-related toxicity. One such concern is radiation-induced heart disease, which remains a significant focus of ongoing investigations.

The aim of this review is to summarize current knowledge on radiation-induced heart disease in breast cancer patients by giving an overview of its epidemiology, risk factors, radiation parameters related to its development, solutions in radiation practice, and prevention. The goal is to raise awareness and maximize prevention of radiation-induced heart disease.

The PubMed database was screened for articles published between January 2013 and November 2023 related to the keywords , , , and . Moreover, by screening the literature lists of these publications, additional articles were added.

Ninety-four relevant papers remained for final review.

Radiation-induced heart disease is a rare complication after breast cancer radiotherapy and represents a clinical spectrum of various cardiovascular conditions. Several heart-sparing techniques have been developed, and more attention has been paid to early diagnosis and prevention of radiation-induced heart disease. However, further research remains important to refine radiotherapy techniques and deepen our understanding for improved prevention and treatment of this condition in the future. This clinical review summarizes the existing evidence and literature on radiation-induced heart disease following modern breast cancer radiotherapy, offering clinical guidance for physicians.

Cardiovascular toxicity is a well-known complication of thoracic radiation therapy (RT), leading to increased morbidity and mortality, but existing techniques to predict cardiovascular toxicity have limitations. Predictive biomarkers of cardiovascular toxicity may help to maximize patient outcomes.

The machine learning optimal biomarker (OBM) method was employed to predict development of cardiotoxicity (based on serial echocardiographic measurements of left ventricular ejection fraction and longitudinal strain) from computed tomography (CT) images in patients with thoracic malignancy undergoing RT. Manual segmentations of 10 cardiovascular objects of interest were performed on pre-treatment non-contrast-enhanced CT simulation images in 125 patients with thoracic malignancy (41 who developed cardiotoxicity and 84 who did not after RT). 1078 features describing morphology, image intensity, and texture for each of these objects were extracted and the top 5 features among them that were most uncorrelated and showed the best ability to discriminate between cardiotoxicity/ no cardiotoxicity were determined. The best combination among all possible combinations among these 5 features that yielded the highest accuracy of prediction on a training data set was selected, an SVM classifier was then trained on this combination, and tested for prediction accuracy on an independent data set. Prediction accuracy was quantified for the optimal features derived from each object.

The best feature combination based on 5 CT-based features derived from the left ventricle had the highest testing prediction accuracy of 0.88 among all objects. Prediction accuracies over all objects ranged from 0.76-0.88. Heart, Left Atrium, Aortic Arch, Thoracic Aorta, and Descending Thoracic Aorta showed the next best accuracy of 0.84. Most optimal features were texture properties based on the co-occurrence matrix.

It is feasible to predict future cardiotoxicity following RT with high accuracy in individual patients with thoracic malignancy from available pre-treatment CT images via machine learning techniques.

Due to respiratory motion, treating sternal metastases with stereotactic body radiotherapy (SBRT) is challenging, often requiring large irradiation volumes to account for target movement. To address this, we implemented a straightforward approach by placing skin fiducial markers near the sternal metastasis, enabling real-time motion synchronization with the CyberKnife® System (Accuray Inc., Sunnyvale, CA). Advances in anti-cancer therapies have significantly extended survival in metastatic patients, increasing their likelihood of requiring re-irradiation and experiencing late toxicities. We present the outcomes of two patients, one with metastatic hepatocellular carcinoma (mHCC) and one with metastatic breast cancer (mBC), who underwent two courses of SBRT for sternal metastases using the CyberKnife® and skin fiducial markers for motion management. Both patients tolerated the treatment well, achieving complete pain relief and durable local control. No late toxicity was observed in the mHCC case, while the mBC patient developed significant left anterior descending artery (LAD) stenosis, which may have been linked to cumulative radiation exposure. Given the known risk of cardiac toxicity associated with radiation therapy, these findings underscore the importance of minimizing cardiac dose to reduce long-term toxicity, particularly in re-irradiation cases.

Cancer and cancer treatment may accelerate the development of cardiovascular disease. With the improved prognosis of cancer survivors, cardiovascular events are increasing in this patient group. However, it is unknown whether the prevalence of coronary atherosclerosis is increased in patients with a history of cancer. This study aims to evaluate the prevalence and severity of coronary atherosclerosis in different age groups of cancer survivors compared to matched controls.

Consecutive cancer survivors aged > 30 years who underwent evaluation for stable coronary artery disease with coronary computed tomography angiography (CCTA) were included in this retrospective study. Propensity score matching was performed and cancer survivors were matched 1:2 to a control population without oncological history. The presence of coronary atherosclerosis was assessed in both groups.

The study population consisted of 312 cancer survivors and 624 matched controls. Median age at CCTA scan was 59.2 [50.3-67.5] years and 66.0% was female. Coronary atherosclerosis was observed in 257 (82.4%) cancer survivors compared to 459 (73.6%) control patients with an Odds Ratio (OR) of 1.68 [95% CI: 1.19-2.36], P = .003. Mainly younger cancer survivors aged between 30 and 59 years had an increased prevalence of coronary atherosclerosis with an OR of 2.21 [95% CI: 1.40-3.49] compared to control patients (P = .001). In addition, thoracic radiotherapy showed a significant association with increased prevalence of atherosclerosis in the younger population with an OR of 3.29 ([95% CI: 1.70-6.38], P < .001).

Patients with a history cancer have an increased prevalence of coronary atherosclerosis on CCTA compared to matched patients without cancer. This effect was most pronounced in younger patients aged 30 to 59 years.

Purpose To evaluate the relationship between cardiac radiation doses and subclinical changes in cardiac function using cardiac MRI during 2 years of follow-up in patients with breast cancer treated with radiation therapy without chemotherapy after lumpectomy. Materials and Methods This prospective multicenter study (NCT03297346) enrolled female individuals with breast cancer treated with radiation therapy between December 2017 and September 2019. Participants underwent cardiac MRI at baseline, 6 months, and 24 months. Cardiac radiation doses were assessed for the whole heart (WH) and right and left ventricles (LV). A persistent decrease in LV global longitudinal strain (GLS) from baseline to the other two measurement points over the 2-year follow-up was considered an adverse subclinical change in cardiac function. Statistical analysis included Wilcoxon tests for continuous variables and odds ratios for risk assessment. Results The study included 138 female participants (mean age, 58.4 years ± 8.0 [SD]). Mean WH and LV doses were 1.42 Gy (IQR, 1.03-2.01) and 1.46 Gy (IQR, 0.64-2.34). At the 2-year follow-up, all participants had reduced LV end-diastolic volume (EDV) (-4.0% ± 13.2; P < .001) and stroke volume (-3.4% ± 15.2; P < .001), preserved LV ejection fraction, and increased LV remodeling (LV mass/EDV ratio) (4.2% ± 18.1; P < .04) without associated symptoms. Twenty-three (16.6%) participants showed a persistent decrease in LV GLS and received higher mean WH and LV doses compared with participants without persistent decrease in LV GLS (WH: 2.09 Gy [IQR, 1.50-2.45] vs 1.36 Gy [IQR, 1.01-1.87], P < .001; LV: 2.40 Gy [IQR, 1.09-2.88] vs 1.34 Gy [IQR, 0.63-2.02], P = .002). The relative changes in LV EDV and LV mass/EDV were -12.7% ± 9.0 versus -2.2% ± 13.3 (P < .001) and 14.2% ± 15.5 versus 2.2% ± 18.1 (P = .002), respectively, in participants with and without a persistent decrease in LV GLS. A higher WH cardiac radiation dose was associated with a higher risk of a persistent decrease in LV GLS (odds ratio, 1.09 [95% CI: 1.02, 1.16]). Conclusion In participants with recent breast cancer radiation therapy, a modest but persistent reduction in LV GLS over a 2-year follow-up period was associated with the cardiac radiation dose. Keywords: Radiotherapy, Magnetic Resonance Imaging, Cardiotoxicity, Strain Clinical trial registration no. NCT03297346 Supplemental material is available for this article. © RSNA, 2025.

To examine the effect of selected cardiovascular disease (CVD) risk factors over time on early cancer outcomes in breast cancer (BC) survivors.

A prospective study was conducted among women aged 20-65 years with an incident invasive BC enrolled in the Breast and Ovarian Surveillance Service (BOSS) Cohort between 2005 and 2013. CVD risk based on selected risk factors was assessed at baseline and two follow-ups. Participants were categorized into low, medium, and high-risk groups. The primary outcome was BC recurrence (distant or local) or second primary cancer (SPC). Kaplan-Meier failure curves and multivariable Cox proportional hazard models were performed to compare the hazards across CVD risk score groups.

A total of 212 women with invasive BC contributed to 2211 person-years (median follow-up 11.7 years), 103 had low, 73 medium, and 36 high CVD risk scores at baseline. In multivariable analyses, BC survivors with medium CVD risk score had 2.09 times higher risk (95%CI = 1.09-4.02; p = 0.027) of recurrence/SPC compared to survivors with low CVD risk score. This association was particularly pronounced in postmenopausal women, those with estrogen receptor-positive BC, regional disease, or newly diagnosed BC. After excluding women taking cardiac medications, a higher risk of recurrence/SPC was also observed among those in the high-CVD-risk-score group, although not significant.

Higher CVD risk score based on selected risk factors was significantly associated with BC recurrence or SPC, particularly in certain subgroups. Monitoring and treating a combination of CVD risk factors in BC survivors may help reduce BC progression.

Radiation-induced coronary artery disease (RI-CAD) is a significant cardiovascular complication for cancer survivors treated with thoracic radiation therapy (RT). Despite advances in RT techniques, exposure to the heart during treatment remains a critical factor influencing long-term cardiac outcomes, particularly in patients with breast and lung cancer. RI-CAD develops due to radiation-induced endothelial injury, inflammation, and accelerated atherosclerosis, presenting a unique and aggressive disease profile. This review explores the pathophysiology, risk factors, and diagnostic advancements for RI-CAD, emphasizing the role of PET in improving patient outcomes.

Multi-day assessments accurately identify patients with left-sided breast cancer who are ineligible for irradiation in Deep Inspiration Breath Hold (DIBH) and minimise on-couch treatment time in those who are eligible. The challenge of implementing multi-day assessments in resource-constrained settings motivated the development of a machine learning (ML) model using data only from the 1st day of assessment to predict DIBH ineligibility.

This prospective cohort study used data from 202 patients collected between January and December 2023 for model development. Patient-related and DIBH assessment-related variables (upper, lower, and average breath-hold amplitude; average breath-hold duration; breath-hold consistency) were included. Nine ML algorithms (and three modelling strategies) were evaluated, and a decision curve analysis was used to select the best model. The best model was temporally validated on a prospective dataset of 47 patients (January to March 2024). Further, a clinical impact study on another prospective cohort of 64 patients (April to August 2024) was performed, to assess its practical utility by comparing its predictions with the clinical team's decision to treat a patient in DIBH or not.

The uncalibrated gradient-boosting ensemble model demonstrated the highest performance [AUC (95 % CI) = 0.803 (0.686-0.941); Recall = 0.526] and net benefit in decision curve analysis. Key predictors included average breath-hold duration and lower breath-hold amplitude levels. The clinical impact study suggests that the model reduces the need for additional DIBH assessments by up to 20 % without misclassifying eligible patients.

The developed ML model accurately predicts DIBH ineligibility using only first-day DIBH assessment data and could be a decision aid for patient selection in resource-constrained or busy departments. External validation is necessary to confirm its generalizability.

Radiation therapy (RT) improves breast cancer outcomes, but cardiac morbidity remains a concern.

This study sought to evaluate changes in cardiac function after RT and the relationship between cardiac dose metrics and echocardiography-derived measures of function.

In a longitudinal cohort study of women with breast cancer, radiation cardiac dose metrics and core lab quantitated echocardiographic measures of cardiac function were evaluated. Dose metrics included the whole heart, left ventricle, right ventricle, and left anterior descending artery (LAD). Echocardiographic measures included left ventricular ejection fraction (LVEF), longitudinal strain, circumferential strain, E/e' (ratio of early diastolic mitral inflow velocity to early diastolic mitral annular tissue velocity), Ea/Es (ventricular arterial coupling; ratio of effective arterial elastance to end systolic elastance), and right ventricular fractional area change. The mean change in echocardiographic measures over time and the association between cardiac dose metrics and echocardiographic measures were estimated by repeated-measures multivariable linear regression via generalized estimating equations.

The cohort included 303 participants (median age 52 years, 33.3% African American) who received adjuvant RT (2010-2019) with a median mean heart dose of 1.19 Gy (Q1-Q3: 0.75-2.61 Gy), were followed over a median of 5.1 years (Q1-Q3: 3.2-7.1 years). Across all participants, there was a modest increase in LVEF (52.1% pre-RT to 54.3% at 5 years; P < 0.001) but a worsening in sensitive measures of function, such as circumferential strain (-23.7% pre-RT to -21.0% at 5 years; P = 0.003). Among left-sided/bilateral breast cancer participants, changes in cardiac function were observed across all parameters (P < 0.05). The maximum LAD dose was associated with a modest worsening in LVEF, longitudinal strain, circumferential strain, and E/e'.

Over a median of 5.1 years, modest changes in cardiac function were observed with RT. Maximum LAD dose was associated with a worsening in systolic and diastolic function parameters.

Radiation-induced cardiac dysfunction (RICD) is a competing cause of morbidity and mortality in patients receiving thoracic radiation therapy (RT). Currently, there are no clinically-validated approaches for early detection of RICD at a time point that affords the potential for mitigation. The goal of this study was to evaluate the potential of global longitudinal strain (GLS) derived from standard-of-care echocardiogram (ECHO) for the early detection of RICD and to assess the association between adverse GLS changes and survival in patients receiving thoracic RT.

A retrospective review of changes in GLS was carried out in patients with primary or secondary lung cancer who received standard-of-care thoracic RT with a mean heart dose of ≥5 Gy and had measurable GLS on ECHOs performed before and after RT. Changes in 2-chamber (2C), 3-chamber (3C), and 4-chamber (4C) GLS and peak average GLS after RT (relative to pre-RT baseline) were quantified. Survival probabilities were estimated in patients with normal versus abnormal GLS.

Thirty-eight patients had measurable GLS before and after RT. Abnormal GLS (defined as <18% or >15% relative decline in GLS after RT from a normal baseline value) was present in 31.6% of patients before RT and 57.9% of patients after RT (P = .012). On paired comparisons, the absolute median reduction (IQR) in 2-chamber, 3-chamber, 4-chamber, and average GLS after RT relative to pre-RT baseline was 1.90 (4.43), 3.00 (3.83), 2.50 (3.63), and 2.25 (3.53), respectively, all P < .001. No statistically significant change in left ventricular ejection fraction was noted after RT. Patients with abnormal GLS after RT had significantly worse survival than those with normal GLS on univariable analysis (P = .049). Despite the small sample size of the study, the survival detriment in patients with abnormal GLS after RT strongly trended toward significance on multivariable analysis (P = .063).

Adverse changes in GLS are detectable on standard-of-care ECHOs and precede significant changes in left ventricular ejection fraction in this cohort of high-risk patients with primary and secondary lung cancer receiving thoracic RT. Thus, ECHO-derived GLS has the potential to serve as an early and noninvasive marker of RICD in this patient population and may enable early adoption of GLS-guided cardioprotective therapy, which has been shown to mitigate cardiac dysfunction in patients with cancer receiving cardiotoxic treatments.

Breast cancer is a prevalent malignancy requiring ongoing treatment advancements. Radiotherapy is vital for reducing recurrence and improving survival. This study evaluates unintended doses to internal mammary lymph nodes and influencing factors in patients at Ankara Bilkent City Hospital's Radiation Oncology Clinic.

We analyzed 44 right-sided breast cancer patients treated with radiotherapy between November 2019 and April 2023. Data on demographics, treatment, and dose-volume histograms were reviewed using various statistical tests.

Median age was 54 years; 88.6% had invasive ductal carcinoma, and 11.4% had ductal carcinoma in situ. Patients received conventional (54.5%) or hypofractionated radiotherapy (45.5%) using intensity-modulated radiotherapy or three-dimensional conformal radiotherapy. Median internal mammary lymph node volume was 7.3 cc with dose variability. Internal mammary lymph nodes V45 dose showed no correlation with internal mammary lymph nodes volume, radiotherapy field, pT stage, or pN stage. However, the nodal stage significantly impacted the internal mammary lymph nodes D95 dose, with higher doses in N1 patients. Wider radiotherapy fields led to increased D95 doses.

The findings highlight the variability in internal mammary lymph nodes doses and the impact of nodal stage and radiotherapy field on dose distribution. Advanced techniques like intensity-modulated radiotherapy can reduce risks, but careful planning is essential.

Understanding internal mammary lymph nodes dose factors can enhance treatment planning and outcomes. Future research should focus on refining guidelines and leveraging technology to improve radiotherapy efficacy.

Radiation-induced cardiotoxicity (RIC) is common in patients receiving thoracic radiation and is a major risk factor for morbidity and mortality. The development of novel approaches for early detection and mitigation of RIC remains an acute unmet need. The objective of this study is to develop a mouse model of RIC that recapitulates the progression of cardiac dysfunction seen in patients receiving thoracic radiation and to develop novel cardiac strain markers that exhibit higher sensitivity in detecting subclinical RIC over existing approaches.

We developed a mouse model of RIC through image guided whole heart irradiation of male C57BL/6J mice using 2 radiation regimens (8 Gy × 5 and 24 Gy × 1). We developed a pipeline for analyzing anatomic and principal strains derived from cardiac magnetic resonance (CMR) imaging obtained at baseline, 3 months, and 6 months following radiation.

Both radiation regimens used for whole heart irradiation caused a progressive decline in both anatomic and principal cardiac strains over time. The minimum principal cardiac strain detected a subclinical decline in cardiac contractility at an earlier time point than the traditional anatomic cardiac strains. We also observed asymmetric changes in contractility at the epicardium and endocardium relative to averaged cardiac strain across the full thickness of the left ventricle following cardiac irradiation, further reinforcing the limitations of existing methods, which do not capture the heterogeneity in cardiac strain changes along the transmural axis.

We have developed a mouse model of RIC that recapitulates time-dependent deterioration in myocardial contractility noted in patients receiving thoracic radiation. We also developed CMR imaging-derived novel principal strain cardiac markers that detect subclinical deterioration in cardiac contractile function earlier than traditional anatomic cardiac strain markers. If successfully translated into patients, our novel approach of measuring CMR imaging-derived cardiac principal strain analysis may enhance the detection of subclinical RIC in patients receiving thoracic radiation.

Patients with premenopausal breast cancer (preBC) usually have long-term survivorship. However, less is known about the risk pattern of subsequent primary cancer (SPC) and noncancer diseases among them. Here, this study aimed to evaluate the risk of developing SPCs and mortality among preBC survivors. In this population-based, retrospective cohort study, 5-year preBC survivors diagnosed at age 20-59 years during 1992-2014, in the 11 Surveillance, Epidemiology and End Result registries were included. Standardized incidence ratio (SIR) and standardized mortality ratio (SMR) were estimated for SPCs and mortality by cause, respectively. Among 181,947 survivors (mean age at diagnosis, 49.1 years; 65.9% White), there were 12,503 SPC cases, 4,280 SPC-related deaths, and 10,591 noncancer-related deaths. SPC risk was increased compared with the general population (SIR 1.06, [95% CI, 1.04-1.08]). The elevated risk was primarily associated with soft tissue cancer, bones/joints cancer, and acute non-lymphocytic leukemia (SIRs 2.01 [95% CI, 1.73-2.33], 1.78 [95% CI, 1.21-2.53], and 1.68 [95% CI, 1.46-1.93], respectively). Young-onset, Asian survivors, those with hormone receptor-negative BC, and initially treated with chemo-radiotherapy were at high-risk. The risk of dying from SPCs was also increased (SMR 1.07, [95% CI, 1.04-1.10]) and featured with similarly vulnerable subpopulations. Survivors of non-White ethnicity had a higher risk of dying from noncancer diseases. This study highlighted the excess risk of developing and dying from SPCs among preBC survivors, suggesting that targeted healthcare is warranted. Strategies for SPCs and noncancer comorbidity management are in great demand to achieve better long-term survivorship among preBC patients.

Cardiotoxicity represents a critical challenge in cancer therapy, particularly in the treatment of thoracic tumors, such as lung cancer and lymphomas, as well as breast cancer. These malignancies stand out for their high prevalence and the widespread use of cardiotoxic treatments, such as chemotherapy, radiotherapy, and immunotherapy. This work underscores the importance of preclinical models in uncovering the mechanisms of cardiotoxicity and developing targeted prevention and mitigation strategies. In vitro models provide valuable insights into cellular processes, enabling the observation of changes in cell viability and function following exposure to various drugs or ionizing radiation. Complementarily, in vivo animal models offer a broader perspective, allowing for evaluating of both short- and long-term effects and a better understanding of chronic toxicity and cardiac diseases. By integrating these approaches, researchers can identify potential mechanisms of cardiotoxicity and devise effective prevention strategies. This analysis highlights the central role of preclinical models in advancing knowledge of cardiotoxic effects associated with common therapeutic regimens for thoracic and breast cancers.