Cancer is a major public health, societal, and economic challenge worldwide. According to Global Cancer Statistics 2022, it is estimated that by 2050, there will be 35 million new cancer cases globally. Although patient survival rates have improved through various therapeutic approaches, including surgery, chemotherapy, and radiotherapy, treatment efficacy remains limited once tumor metastasis occurs. Among various cancer treatment strategies, radiotherapy plays a crucial role. Along with surgery and chemotherapy, radiotherapy is a cost-effective single-modality treatment, accounting for approximately 5% of total cancer care costs. The use of radiosensitizing agents such as histone deacetylase inhibitors, 2-deoxy-d-glucose, enterolactone, and squalene epoxidase can enhance radiotherapy effectiveness. Recent radiosensitization methods involve physical stimuli and chemical radiosensitizers. However, improving their efficacy, durability, and overcoming radioresistance remain significant challenges. This review first introduces current applications of radiotherapy in cancer treatment, the molecular mechanisms underlying its anticancer effects, and its side effects. Second, it discusses the main types of radiosensitizers, their latest applications, and recent challenges in cancer treatment. Finally, it emphasizes on clinical trials of radiosensitizing agents and explores potential biomarkers for radiotherapy response in cancer. Multifunctional nanoparticles have shown greater clinical applicability than single-functional nanoparticles. Future research will focus on enhancing the drug-carrying capacity of nanomaterials to further improve radiotherapy outcomes.

Breast cancer (BC) survivors may be at increased risk of developing second cancers compared to those without BC diagnosis due to shared risk factors and potential carcinogenic effects of cancer therapy. Lung cancer (LC) is the most common second primary cancer among BC survivors. This study aimed to evaluate the association between BC and the subsequent incidence of LC.

Women aged 55-74 were identified from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The risk of incident LC was compared by BC status using a multivariable Cox regression model with BC and smoking exposures incorporated as time-updated variables.

75,951 females from the PLCO trial were identified, with 5808 diagnosed with BC after enrollment. The unadjusted incidence rate (IR) of the second LC was significantly higher among BC survivors than non-BC participants (231 vs. 172 per 100,000 person-years). The adjusted hazard ratio (HR) for the second primary LC associated with BC diagnosis was 1.24 (95% CI: 1.03-1.49).

BC diagnosis was an independent risk factor for the development of second primary LC. Consequently, BC survivors may derive benefits from enhanced LC screening interventions.

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.

Breast cancer is the most common cancer among women. Second primary malignancies (SPMs) related to radiotherapy are significant complications. This study aims to investigate the correlation between radiotherapy and the occurrence of SPMs in breast cancer patients with different estrogen receptor statuses.

We used data from the Surveillance, Epidemiology, and End Results (SEER) database, selecting estrogen receptor(+) and estrogen receptor(-) breast cancer patients from 1990 to 2015, with SPMs as the outcome measure. Fine-Gray competing risks regression and Poisson regression were employed to analyze the relationship between radiotherapy and the risk of SPMs in different estrogen receptor status groups.

Radiotherapy was associated with an increased risk of lung cancer, melanoma, non-Hodgkin lymphoma, and leukemia in estrogen receptor(+) patients. In estrogen receptor(-) patients, radiotherapy was linked to an increased risk of brain cancer and leukemia. The cumulative incidence, standardized incidence ratio, and subgroup analyses showed consistent results. In the dynamic assessment of radiotherapy-related risks, estrogen receptor(+) patients aged 50-70 exhibited a higher risk of leukemia and melanoma. Lung cancer risk was highest during a latency period of 20-30 years, while melanoma, non-Hodgkin lymphoma, and leukemia risks peaked within the first 10 years. For estrogen receptor(-) patients, brain cancer risk was higher between ages 50 and 70, and leukemia risk was elevated between ages 20 and 50.

Postoperative radiotherapy for breast cancer is associated with an increased risk of SPMs, with risks varying by estrogen receptor status and SPM type. Further research into the prevention of radiotherapy-related SPMs in different estrogen receptor status groups is crucial.

To assess the dose-sparing capabilities of a yaw-limited volumetric modulated arc therapy (YL_VMAT) beam setup for adjacent organs at risk (OAR) in comparison with 3D-conventional radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT) and conventional VMAT for radiation therapy in left-sided breast cancer patients.

In total, 80 treatment plans for 20 patients, of which 10 patients underwent CT-scans in deep inspiration breath-hold (DIBH) and 10 patients in free-breathing (FB) technique. Besides generally tangential-weighted static and IMRT beams, VMAT treatment plans with approximately 270° arc length have been compared and analyzed to a multi-field, yaw-adapted, unconventional partial VMAT technique retrospectively. The prescription dose was set to 40.05 Gy in 15 fractions.

We achieved a more pronounced steeper dose falloff directed from the thoracic wall to the adjacent lung tissue resulting in a significantly better ipsilateral lung and considerably cardiac dose sparing using the YL_VMAT method in general. Compared with standard techniques (IMRT, VMAT, 3D-CRT), YL-VMAT in combination with DIBH can achieve lower mean doses for the heart (1.05 Gy vs. 1.73 Gy, 2.16 Gy and 1.44 Gy), the left anterior descending (LAD) artery (3.68 Gy vs. 6.53 Gy, 5.13 Gy and 8.64 Gy) and the left lung (3.59 Gy vs. 5.39 Gy, 4.79 Gy and 5.87 Gy), respectively. Also with FB, the corresponding mean doses for the left lung and cardiac structures were lower with the YL-VMAT method than with IMRT (heart: 1.70 Gy vs. 2.44 Gy; LAD: 6.50 Gy vs. 11.97 Gy; left lung: 3.10 Gy vs. 4.72 Gy), VMAT (heart: 1.70 Gy vs. 2.52 Gy; LAD: 6.50 Gy vs. 9.06 Gy; left lung: 3.10 Gy vs. 4.46 Gy) and 3D-CRT (heart: 1.70 Gy vs. 2.78 Gy; LAD: 6.50 Gy vs. 15.09 Gy; left lung: 3.10 Gy vs. 5.77 Gy). In addition, we found out superiority of YL_VMAT for the V5, V10, and V20 Gy to the left lung. For DIBH and FB, all differences for the left lung were significant, with p < 0.05.

With the YL_VMAT technique, dose exposures to radiosensitive OARs like the lung, heart and LAD artery can be reduced considerably to very low values in comparison to already established planning methods. The benefits must be weighed against the potential risks induced by an increased dose exposure to the contralateral breast.

Significance: This review investigates how radiation therapy (RT) increases the risk of delayed cardiovascular disease (CVD) in cancer survivors. Understanding the mechanisms underlying radiation-induced CVD is essential for developing targeted therapies to mitigate these effects and improve long-term outcomes for patients with cancer. Recent Advances: Recent studies have primarily focused on metabolic alterations induced by irradiation in various cancer cell types. However, there remains a significant knowledge gap regarding the role of chronic metabolic alterations in normal cells, particularly vascular cells, in the progression of CVD after RT. Critical Issues: This review centers on RT-induced metabolic alterations in vascular cells and their contribution to senescence accumulation and chronic inflammation across the vasculature post-RT. We discuss key metabolic pathways, including glycolysis, the tricarboxylic acid cycle, lipid metabolism, glutamine metabolism, and redox metabolism (nicotinamide adenine dinucleotide/Nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADP+)/NADPH). We further explore the roles of regulatory proteins such as p53, adenosine monophosphate-activated protein kinase, and mammalian target of rapamycin in driving these metabolic dysregulations. The review emphasizes the impact of immune-vascular crosstalk mediated by the senescence-associated secretory phenotype, which perpetuates metabolic dysfunction, enhances chronic inflammation, drives senescence accumulation, and causes vascular damage, ultimately contributing to cardiovascular pathogenesis. Future Directions: Future research should prioritize identifying therapeutic targets within these metabolic pathways or the immune-vascular interactions influenced by RT. Correcting metabolic dysfunction and reducing chronic inflammation through targeted therapies could significantly improve cardiovascular outcomes in cancer survivors. Antioxid. Redox Signal. 00, 000-000.

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.

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.

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.

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.

Breast cancer (BC) is the most common malignancy with a poor prognosis. Radiotherapy is one of the leading traditional treatments for BC. However, radiotherapy-associated secondary diseases are severe issues for the treatment of BC. The present study integrated multi-omics data to investigate the molecular and epigenetic mechanisms involved in post-radiation BC. The differences in the expression of radiation-associated genes between post-radiation and pre-radiation BC samples were determined. Enrichment analysis revealed that these radiation-associated genes involved diverse biological functions and pathways in BC. Combining epigenetic data, we identified radiation-associated genes whose transcriptional changes might be associated with aberrant methylation. Then, we identified potential therapeutic targets and chemical drugs for post-radiation BC patient treatment by constructing a drug-target association network. Specifically, four radiation-associated genes (CD248, CCDC80, GADD45B, and MMP2) whose increased expression might be regulated by hypomethylation of the corresponding enhancer region were found to have excellent diagnostic effects and clinical prognostic value. Finally, we further used independent samples to verify CD248 expression and established a simple epigenetic regulatory model. In summary, this study provides novel insights for understanding the regulation of target genes mediated by DNA methylation and developing potential biomarkers for radiation-associated secondary diseases in BC.

Breast cancer, the most prevalent cancer affecting women worldwide, poses a significant cardio-oncological burden. Despite advancements in novel therapeutic strategies, anthracyclines, HER2 antagonists, and radiation remain the cornerstones of oncological treatment. However, each carries a risk of cardiotoxicity, though the molecular mechanisms underlying these adverse effects differ. Common mechanisms include DNA damage response, increased reactive oxygen species, and mitochondrial dysfunction, which are key areas of ongoing research for potential cardioprotective strategies. Since these mechanisms are also essential for effective tumor cytotoxicity, we explore tumor-specific effects, particularly in hereditary breast cancer linked to BRCA1 and BRCA2 mutations. These genetic variants impair DNA repair mechanisms, increase the risk of tumorigenesis and possibly for cardiotoxicity from treatments such as anthracyclines and HER2 antagonists. Novel therapies, including immune checkpoint inhibitors, are used in the clinic for triple-negative breast cancer and improve the oncological outcomes of breast cancer patients. This review discusses the molecular mechanisms underlying BRCA dysfunction and the associated pathological pathways. It gives an overview of preclinical models of breast cancer, such as genetically engineered mouse models, syngeneic murine models, humanized mouse models, and various in vitro and ex vivo systems and models to study cardiovascular side effects of breast cancer therapies. Understanding the underlying mechanism of cardiotoxicity and developing cardioprotective strategies in preclinical models are essential for improving treatment outcomes and reducing long-term cardiovascular risks in breast cancer patients.

Ancillary breast cancer (BC) radiation therapy (RT), particularly associated with chemotherapy, increases the risk of coronary artery disease (CAD). However, it remains unclear whether this risk also applies to isolated contemporary radiotherapy without chemotherapy.

Seventy-five BC patients (35 left-sided and 40 right-sided) treated with RT and available dosimetry, prospectively underwent Agatston calcium score (CAC) and coronary CT angiography (CTCA) a median of 11 ± 1 years later and were compared to 75 age- and cardiovascular (CV) risk factor-matched female controls without a history of cancer.

BC patients and controls had similar ages (62 ± 7 vs. 61 ± 7 years, p = 0.63), CV risk factors and estimated Score2/OP risk (3.8 % IQR 2.6-6 vs. 3.3 % IQR 2.3-5.4, p = 0.52). CAC scores (0 IQR 0-79 vs. 0 IQR 0-34, p = 0.62) and age-predicted percentile CAC scores (p = 0.61) were similar between BC patients and controls, with no significant difference between left- and right-sided RT. Multivariable analysis revealed that CAC scores in BC patients were predicted only by a family history of CAD and by Score-2/OP risk, but not by cardiac radiation exposure. By CTCA 68 % of BC patients had no or very mild coronary disease, and only 14 % had more than moderate stenosis (>50 %), which was predicted by CAC scores > 79 (AUC = 0.97).

Eleven years post-treatment with isolated contemporary RT for BC, patients exhibited similar CAC severity as age- and risk factor-matched controls. CAC was associated only with CV risk factors, but not radiation dose, suggesting contemporary RT for BC is not linked to higher subclinical CAD prevalence.

This study investigates scintillation dosimetry coupled with Cherenkov imaging for in vivo dose monitoring during whole breast radiation therapy (WBRT). Given recent observations of excess dose to the contralateral breast (CB), in vivo dosimetry (IVD) could help ensure accurate dose delivery and decrease risks of secondary cancer. This work presents a rapid, streamlined alternative to traditional IVD, providing direct visualization of measurement location relative to the treatment field on the patient.

Ten WBRT patients consented under an institutional review board-approved protocol were monitored with scintillation dosimetry and always-on Cherenkov imaging, on both their treated and CB for 1 to 3 fractions. Scintillator dosimeters, small plastic discs 1 mm thick and 15 mm in diameter, were calibrated against optically stimulated luminescent dosimeters (OSLDs) to generate an integral output-to-dose conversion, where integral output is measured in postprocessing through a custom fitting algorithm. The discs have been extensively characterized in a previous study for various treatment conditions including beam energy and treatment geometry.

A total of 44 dosimetry measurements were evaluated, including 22 treated breast and 22 CB measurements. After integral output-to-dose calibration, in vivo scintillator dosimeters exhibited high linearity (R2 = 0.99) with paired OSLD readings across all patients. The difference between scintillation and OSLD dose measurements averaged 2.8% of the prescribed dose, or an absolute dose difference of approximately 7 cGy.

Integration of scintillation dosimetry with Cherenkov imaging offers an accurate, rapid alternative for in vivo dose verification in WBRT, circumventing the limitations of conventional point dosimeters. The additional benefit of visualizing measurement locations relative to the treatment field provides users an enhanced understanding of results and allows for detection of high dose gradients. Future work will explore the applicability of this technique across a broader range of radiation therapy treatments, aiming to streamline IVD practices.

Breast radiation treatment has been linked to complications such as pneumonitis and cardiac toxicity, necessitating dose optimization. This study aims to determine the optimal integration plan of volumetric modulated arc therapy (VMAT) and three-dimensional conformal radiotherapy (3DCRT) in a deep inspiration breath-hold regimen.

CT imaging data from twenty patients with breast or chest wall cancer, either right or left-sided, and with supraclavicular and internal mammary chain lymph nodes were retrieved. The CT data planned with a hybrid VMAT of three different weighting proportions: 30 % using 3DCRT and 70 % using VMAT, 50 % using 3DCRT and 50 % using VMAT, and 70% using 3DCRT and 30 % using VMAT and compared with full 3DCRT and full VMAT plan (classic and five arc design).

The homogeneity and conformity indices were better in the hybrid VMAT plans than in plans using VMAT or 3DCRT alone (P<0.005). Results of all hybrid VMAT plans showed a considerable drop of volumes receiving more than 4Gy, 8Gy or 16Gy in the ipsilateral lung compared to the full VMAT plan (P<0.001). There was a noticeable decrease in the mean dose to the heart and the dose in 5% of the contralateral breast in the plan using 70 % 3DCRT and 30 % VMAT compared to full VMAT (P<0.001). The plan using 70 % 3DCRT and 30% VMAT achieved a balance between the target and surrounding areas, compared to using only 3DCRT or VMAT.

A hybrid plan using 70 % 3DCRT contribution achieved a balanced outcome for breast or chest wall irradiation, considering both planning target volume and organs at risk. Utilizing our VMAT arc design, incorporating one shortened arc can significantly reduce doses to organs at risk further. It is important to consider the patient's anatomy when making this decision.

Although anthracycline-related cardiotoxicity is widely studied, only a limited number of echocardiographic studies have assessed cardiac function in breast cancer survivors (BCSs) beyond ten years from anthracycline treatment, and the knowledge of long-term cardiorespiratory fitness (CRF) in this population is scarce. This study aimed to compare CRF assessed as peak oxygen uptake (V̇O2), cardiac morphology and function, and cardiovascular (CV) risk factors between long-term BCSs treated with anthracyclines and controls with no history of cancer.

The CAUSE (Cardiovascular Survivors Exercise) trial included 140 BCSs recruited through the Cancer Registry of Norway, who were diagnosed with breast cancer stage II to III between 2008 and 2012 and had received treatment with epirubicin, and 69 similarly aged activity level-matched controls. All the participants underwent blood sampling, blood pressure measurements, echocardiography and cardiopulmonary exercise testing from October 2020 to August 2022.

BCSs were aged 59 ± 6 years and had received a cumulative dose of 357 (243 to 366) mg/m2 of epirubicin on average 11 ± 1 years before inclusion. There was no difference between BCSs and controls with respect to peak V̇O2 (27.6 ± 5.4 mL/kg/min vs. 27.1 ± 5.4 mL/kg/min, P = 0.25), 2D left ventricular ejection fraction (57 ± 3% vs. 57 ± 3%, P = 0.43), left ventricular global longitudinal strain (-20.5 ± 1.0% vs. -20.6 ± 1.0%, P = 0.46) or the proportion with N-terminal pro-brain natriuretic peptide ≥ 125 (22% vs. 20%, P = 0.93). The proportions with hypertension, dyslipidemia or diabetes did not differ between the groups.

We found that CRF, cardiac function, and CV risk profile in BCSs examined a decade after treatment with anthracyclines were similar to that in women with no history of cancer.

clinicaltrials.gov (NCT04307407) https://clinicaltrials.gov/ct2/show/NCT04307407 .

Radiotherapy plays an essential role in the treatment of breast cancer (BC). Recent advances in treatment technology and radiobiological knowledge have a major impact in BC patients with locoregional disease as the majority are now long-term survivors. Over the last three decades, intensity-modulated radiotherapy (IMRT), volumetric-modulated arc therapy (VMAT) and deep inspiration breath-hold (DIBH) techniques, together with the increasing adoption of moderately hypofractionated and ultra-hypofractionated treatment schedules as well as the possibility to offer partial breast radiotherapy to a well-defined patient subset have significantly changed radiotherapy for BC patients. As dose-volume constraints (DVCs) have to be adapted to these new treatment paradigms we have reviewed available evidence-based data concerning dose-constraints for the main organs at risk (OARs) that apply to the treatment of whole breast/chest wall radiotherapy, whole breast/chest wall radiotherapy including regional nodal irradiation (RNI) and partial breast irradiation (PBI), for the most relevant fractionation schedules that have been introduced recently. This narrative review provides a comprehensive summary that may help to harmonize treatment planning strategies.

This study aimed to assess the irradiation techniques-three-dimensional conformal radiotherapy (3DCRT), RapidArc (RArc), and hybrid RapidArc (h-RArc)-for left-sided breast cancer patients, focusing on dose distribution in the planning target volume (PTV) and organs at risks (OARs).

This study enrolled 20 patients diagnosed with early-stage left-sided breast cancer. All patients received a prescribed dose of 40.05 Gy in 15 fractions (2.67 Gy per fraction), optimized to achieve 95% dose coverage to 95% of the PTV. The dosimetric variations across the three treatment plans for the 20 patients were examined using a one-way ANOVA test. P <0.05 was regarded as statistically significant.

In the 3DRCT plan, D95% of the PTV was 37.21 ± 0.51 Gy. This value was significantly increased to 39.43 ± 0.27 Gy in the RArc plan (P = 0.001) and to 38.47 ± 0.19 Gy in the h-RArc plan (P = 0.630). The RArc plans demonstrated a superior homogeneity index of 0.12 ± 0.02 compared to both 3DCRT (0.18 ± 0.02) and h-RArc (0.13 ± 0.02). When comparing the increase in monitor units (MUs), h-RArc showed a 62.82% increase over 3D-CRT, whereas demonstrating a 38.05% decrease compared to RArc (P = 0.000).

h-RArc treatment plans for breast cancer may be recommended due to their superior and consistent PTV dose coverage and sparing of OARs, in comparison to both 3DRCT and RArc plans. These h-RArc plans are characterized by reduced MU and beam on time, as well as a less low volume dose when compared to RArc plans.

While there is a growing amount of data on the cardiac toxicity of radiotherapy (RT) in relation to its impact on cardiac sub-structures (CSS), there are only few studies addressing this issue in patients followed for esophageal cancer (ESOC). We aimed to evaluate the association between independent parameters of dose received by CSS and major cardiac events (MACEs) in this population.

We retrospectively analyzed 122 patients treated with exclusive RT or chemo-RT for ESOC. Heart and CSS i.e. right atrium, left atrium (LA), right ventricle, left ventricle and myocardium, have been automatically segmented, and dose volume histogram were extracted. Cardiac events were collected focusing on the occurrence of MACEs of grade 3 or higher (G3+) and grade 4 or higher (G4+) according to the CTCAE v5.0.

With a median follow-up of 21.9 months and in a population of high to very high cardiovascular risk (95.5%), 21 (17.2%) and 9 (7.4%) patients had G3 + and G4 + MACEs with a respective median time to event of 13.05 and 9.8 months. After multivariate analysis and among all heart and CSS-based dosimetric features, only the volume of LA receiving 15 Gy or more (V15LA) remained significantly associated with the G3 + and G4 + MACEs. The use of volumetric modulated arctherapy significantly reduced V15LA compared with 3D conformal RT.

In a cohort of ESOC patients treated with exclusive RT, incidence of MACEs was associated with V15LA, underlining the importance of CSS. These high cardiovascular (CV) risk patients should benefit from standard CV assessment and strict control of their risk factors.

Ionizing radiation is widely used in various industrial and medical applications, resulting in increased exposure for certain populations. Lessons from radiation accidents and occupational exposure have highlighted the cardiovascular and cerebrovascular risks associated with radiation exposure. In addition, radiation therapy for cancer has been linked to numerous cardiovascular complications, depending on the distribution of the dose by volume in the heart and other relevant target tissues in the circulatory system. The manifestation of symptoms is influenced by numerous factors, and distinct cardiac complications have previously been observed in different groups of patients with cancer undergoing radiation therapy. However, in contemporary radiation therapy, advances in treatment planning with conformal radiation delivery have markedly reduced the mean heart dose and volume of exposure, and these variables are therefore no longer sole surrogates for predicting the risk of specific types of heart disease. Nevertheless, certain cardiac substructures remain vulnerable to radiation exposure, necessitating close monitoring. In this Review, we provide a comprehensive overview of the consequences of radiation exposure on the cardiovascular system, drawing insights from various cohorts exposed to uniform, whole-body radiation or to partial-body irradiation, and identify potential risk modifiers in the development of radiation-associated cardiovascular disease.

In patients with right-sided breast cancer the liver can be partially irradiated during adjuvant radiotherapy (RT). We aimed to determine breast cancer RT effects on liver using with magnetic resonance elastography (MRE) and biological results.

This retrospective study enrolled 34 patients diagnosed with right-sided breast cancer who underwent adjuvant RT. Liver segment assessments were conducted using MRE for all participants. Additionally, a complete blood count and liver enzyme analysis were performed for each patient. All measurements were taken both prior to the initiation and upon completion of RT.

A statistically significant difference was found in ALT (p = 0.015), ALP (p = 0.026), total protein (p = 0.037), and albumin (p = 0.004) levels before and after RT. The highest mean liver stiffness (kPa) value was recorded in segment 8, while the lowest was observed in segment 6. A weak but statistically significant positive correlation was found between segment 5 stiffness and liver volume (p = 0.039). Additionally, a statistically significant positive correlation was detected between ALP levels and the stiffness values in segment 4A (p = 0.020) and segment 6 (p = 0.003). Conversely, a weak negative correlation was observed between the stiffness values in segment 8 and post-RT total protein levels (p = 0.031).

MRE can help us identify the level of fibrotic stiffness in the liver segments within the RT area without establishing clinical symptoms. MRE can support the clinician in evaluating the liver functions of right breast cancer patients who underwent RT. We assume these results will facilitate new studies with a large number of patients on MRE imaging at certain intervals in the follow-up of patients with right breast cancer who received RT before the development of radiation-induced liver disease (RILD).

The study aims to emphasize the clinical importance of the Deep Inspiration Breath Hold (DIBH) technique by quantifying its dosimetric advantages over Free Breathing (FB) in reducing radiation exposure to the heart, liver, and lungs for right-sided breast cancer patients. This evidence supports its potential for routine clinical use to mitigate radiation-induced toxicity.

A systematic retrieval of controlled trials comparing DIBH and FB techniques in postoperative radiotherapy for right-sided breast cancer was conducted utilizing the PubMed, Embase, Cochrane Library, and Web of Science databases. The primary outcomes assessed included the doses of adjacent normal tissues (heart, liver, and lungs). Summary standardized mean differences (SMD) along with 95% confidence intervals (CI) were computed, respectively. StataMP 17 software was selected to perform data analysis.

The study encompassed an analysis of 313 patients derived from seven online studies, comprising 168 individuals in the DIBH group and 269 individuals in the FB group. The findings indicated that the DIBH group received significantly lower irradiation doses to the heart, liver, and lungs in comparison to the FB group, with statistical significance (heart dose: SMD = -0.63, 95% CI -0.85 to -0.41, P < 0.05; liver dose: SMD = -1.15, 95% CI -1.91 to -0.38, P < 0.05; lung dose: SMD = -0.79, 95% CI -1.23 to -0.35, P < 0.05).

This meta-analysis indicated that the application of DIBH during postoperative radiotherapy for right-sided breast cancer markedly decreases radiation exposure to the heart, liver, and lungs, while maintaining consistent tumor dose coverage.

Not applicable.

The evolution of antitumor therapies has significantly improved cancer prognosis but has concurrently resulted in cardiovascular toxicities. Understanding the biological mechanisms behind these toxicities is crucial for effective management. Immunotherapy-related cardiovascular toxicities are primarily mediated by immune cells and secreted cytokines. Chemotherapy may cause cardiovascular damage through autophagy disruption and mitochondrial dysfunction. Targeted therapies can induce toxicity through endothelin-1 (ET-1) production and cardiac signaling disruption. Radiotherapy may lead to cardiomyopathy and myocardial fibrosis by affecting endothelial cells, triggering inflammatory responses and accelerating atherosclerosis. This review provides insights into these mechanisms and strategies, aiming to enhance the clinical prevention and treatment of cardiovascular toxicities.

We introduced an adapted Lyman normal-tissue complication probability (NTCP) model, incorporating clinical risk factors and censored time-to-event data, to estimate the risk of major adverse cardiac events (MACE) following left breast cancer radiotherapy (RT).

Clinical characteristics and MACE data of 1100 women with left-side breast cancer receiving postoperative RT from 2005 to 2017 were retrospectively collected. A modified generalized Lyman NTCP model based on the individual left ventricle (LV) equivalent uniform dose (EUD), accounting for clinical risk factors and censored data, was developed using maximum likelihood estimation. Subgroup analysis was performed for low-comorbidity and high-comorbidity groups.

Over a median follow-up 7.8 years, 64 patients experienced MACE, with higher mean LV dose in affected individuals (4.1 Gy vs. 2.9 Gy). The full model accounting for clinical factors identified D50 = 43.3 Gy, m = 0.59, and n = 0.78 as the best-fit parameters. The threshold dose causing a 50 % probability of MACE was lower in the high-comorbidity group (D50 = 30 Gy) compared to the low-comorbidity group (D50 = 45 Gy). Predictions indicated that restricting LV EUD below 5 Gy yielded a 10-year relative MACE risk less than 1.3 and 1.5 for high-comorbidity and low-comorbidity groups, respectively.

Patients with comorbidities are more susceptible to cardiac events following breast RT. The proposed modified generalized Lyman model considers nondosimetric risk factors and addresses incomplete follow-up for late complications, offering comprehensive and individualized MACE risk estimates post-RT.

The population aged ≥90 years is increasing worldwide, yet nearly 50% of elderly breast cancer (BC) patients receive suboptimal treatments, resulting in high rates of BC-related mortality. We analyzed clinical and survival outcomes of nonagenarian BC patients to identify effective treatment strategies.

This single-institution retrospective cohort study analyzed patients aged ≥90 years diagnosed with stage I-III BC between 2007 and 2018. Patients were categorized into three treatment groups: traditional surgery (TS), performed according to local guidelines; current-standard surgery (CS), defined as breast surgery without axillary surgery (in concordance with 2016 Choosing Wisely guidelines) and/or cavity shaving; and non-surgical treatment (NS). Clinicopathological features were recorded and recurrence rates and survival outcomes were analyzed.

We collected data from 113 nonagenarians with a median age of 93 years (range 90-99). Among these patients, 43/113 (38.1%) underwent TS, 34/113 (30.1%) underwent CS, and 36/113 (31.9%) underwent NS. The overall recurrence rate among surgical patients was 10.4%, while the disease progression rate in the NS group was 22.2%. Overall survival was significantly longer in surgical patients compared with NS patients (p = 0.04). BC-related mortality was significantly higher in the NS group than in the TS and CS groups (25.0% vs. 0% vs. 7.1%, respectively; p = 0.01). There were no significant differences in overall survival and disease-free survival between the TS and CS groups (p = 0.6 and p = 0.8, respectively), although the TS group experienced a significantly higher overall postoperative complication rate (p < 0.001).

Individualized treatment planning is essential for nonagenarian BC patients. Surgery, whenever feasible, remains the treatment of choice, with CS emerging as the best option for the majority of patients.

Background/Objectives: Despite advancements in treatment for patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC), overall survival (OS) remains poor. The specific effects of varying heart and lung doses on OS in LA-NSCLC patients have not been thoroughly investigated, especially their combined impact on survival. This study aimed to examine the impact on OS of both individual and combined heart and lung doses in patients with LA-NSCLC treated with radiotherapy over a three-year follow-up period. Methods: A total of 120 patients who received definitive radiotherapy for LA-NSCLC (stage III, 92.5%) from January 2015 to January 2020 were retrospectively reviewed. The endpoint in this study was OS. Each patient was followed for a fixed period of three years. Results: Univariate Cox regression analysis showed that OS was significantly related to mean heart dose (MHD, hazard ratio [HR], 3.4 [1.8-6.3]; p < 0.001), pericardium V40 (HR, 3.2 [1.7-6.0]; p < 0.001), and total lung V20 (HR, 2.6 [1.4-5.0]; p = 0.003), and these were independent predictors for worse OS in multivariate analysis. Kaplan-Meier curve analysis with log-rank tests revealed that survival was significantly worse in patients with higher MHD (p < 0.001), pericardium V40 (p < 0.001), and total lung V20 (p = 0.002). Combining MHD and total lung V20, and pericardium V40 and total lung V20 provided enhanced risk stratification for OS (p < 0.001 for both combinations). Conclusions: The combination of heart and lung doses provided enhanced and more detailed risk stratification in prediction of OS for a fixed period of three years in LA-NSCLC patients treated with radiotherapy.

Deep inspiration breath hold (DIBH) is an effective technique for reducing heart exposure during radiotherapy for left-sided breast cancer. Despite its benefits, cost considerations and its impact on workflow remain significant barriers to widespread adoption.

This study aimed to assess the cost-effectiveness of DIBH and compare its operational, financial, and clinical outcomes with free breathing (FB) in breast cancer treatment.

Treatment plans for 100 patients with left-sided breast cancer were generated using both DIBH and FB techniques. Dosimetric data, including the average mean heart dose, were calculated for each technique and used to estimate the cardiotoxicity of radiotherapy. A state-transition microsimulation model based on SCORE2 (Systematic Coronary Risk Evaluation) algorithms projected the effects of DIBH on cardiovascular outcomes and quality-adjusted life-years (QALYs). Costs were calculated from a provider perspective using time-driven activity-based costing, applying a willingness-to-pay threshold of €40,000 for cost-effectiveness assessment. A discrete event simulation model assessed the impacts of DIBH vs FB on throughput and waiting times in the radiotherapy workflow.

In the base case scenario, DIBH was associated with an absolute risk reduction of 1.72% (95% CI: 1.67%-1.76%) in total cardiovascular events and 0.69% (95% CI: 0.67%-0.72%) in fatal cardiovascular events over 20 years. Additionally, DIBH was estimated to provide an incremental 0.04 QALYs (95% CI: 0.05-0.05) per left-sided breast cancer patient over the same time period. However, DIBH increased treatment times, reducing maximum achievable throughput by 12.48% (95% CI: 12.36%-12.75%) and increasing costs by €617 per left-sided breast cancer patient (95% CI: €615-€619). The incremental cost-effectiveness ratio was €14,023 per QALY.

Despite time investments, DIBH is cost-effective in the Belgian population. The growing adoption of DIBH may benefit long-term cardiovascular health in breast cancer survivors.

Data evaluating cardiovascular disease (CVD) risk by cancer treatment among young women (≤ 40 years) with breast cancer are limited.

Among 372 five-year breast cancer survivors aged 30-40 years from the Young Women's Breast Cancer Study, we assessed the association of cancer treatments (anthracyclines, trastuzumab, radiation/laterality, endocrine therapy) and excess heart age (difference between predicted 10-year CVD risk as assessed by adapted Framingham Risk Score and chronological age), prevalent elevated excess heart age (≥ 2 years), and worsening excess heart age (change of ≥ 2 excess heart age years) at breast cancer diagnosis and two- and five-year follow-up using multivariable linear and logistic regressions.

Most women had stage I or II (79%), ER + (71%), or PR + (65%) breast cancer. At diagnosis, women had little excess heart age by treatment receipt (range of means = -0.52,0.91 years). Left-sided radiation (β = 2.49,SE = 0.96,p = 0.01) was associated with higher excess heart age at five-year follow-up. For prevalent elevated excess heart age (two-year = 26%;five-year = 27%), women treated with right-sided radiation had increased risk at two-years (OR = 2.17,95%CI = 1.12-4.19), yet at five-years, associations were observed after any radiation (OR = 1.92,95%CI = 1.09-3.41), especially after left-sided (OR = 2.13,95%CI = 1.09-3.41) radiation. No associations were observed between systemic treatments and prevalent elevated excess heart age or any treatments with worsening excess heart age.

Among young breast cancer survivors, radiation, but not other cancer treatments, was associated with elevated excess heart age.

CVD risk tools that incorporate cancer treatment, such as radiation, are needed to identify high risk young breast cancer survivors given the long survivorship and long latency of cardiovascular disease.

In breast cancer radiation therapy, minimizing radiation-related risks and toxicity is vital for improving life expectancy. Tailoring radiotherapy techniques and treatment positions can reduce radiation doses to normal organs and mitigate treatment-related toxicity. This study entailed a dosimetric comparison of six different external beam whole-breast irradiation techniques in both supine and prone positions. We selected fourteen breast cancer patients, generating six treatment plans in both positions per patient. We assessed target coverage and organs at risk (OAR) doses to evaluate the impact of treatment techniques and positions. Excess absolute risk was calculated to estimate potential secondary cancer risk in the contralateral breast, ipsilateral lung, and contralateral lung. Additionally, we analyzed the distance between the target volume and OARs (heart and ipsilateral lung) while considering the treatment position. The results indicate that prone positioning lowers lung exposure in X-ray radiotherapy. However, particle beam therapies (PBTs) significantly reduce the dose to the heart and ipsilateral lung regardless of the patient's position. Notably, negligible differences were observed between arc-delivery and static-delivery PBTs in terms of target conformity and OAR sparing. This study provides critical dosimetric evidence to facilitate informed decision-making regarding treatment techniques and positions.

The optimal radiotherapy technique for cardiac sparing in left-sided early breast cancer (EBC) is not clear. In this context, the aim of our dosimetric study was to compare cardiac and lung doses according to the type of radiotherapy - whole breast irradiation (WBI), external partial breast irradiation (PBI), and multicatheter interstitial brachytherapy-accelerated partial breast irradiation (MIB-APBI). The dosimetric results with the WBI and PBI were calculated with and without DIBH.

Dosimetric study of 23 patients treated with WBI, PBI, with and without DIBH, or MIB-APBI. The prescribed dose was 40 Gy in 15 fractions for WBI and PBI and 34 Gy in 10 fractions (bid) for MIB-APBI. Doses to the organs-at-risk (OAR) - heart, left anterior descending coronary artery (LAD), left ventricle (LV), and left lung - were recalculated to the equivalent dose in 2-Gy fractions (EQD2).

The addition of DIBH significantly reduced EQD2 doses to all OARs (except for the left lung maximal dose) in WBI and PBI. MHD values were 0.72 Gy for DIBH-WBI, 1.01 Gy for MIB-APBI and 0.24 Gy for DIBH-PBI. There were no significant differences in cardiac doses between WBI with DIBH and PBI without DIBH. DIBH-PBI resulted in significantly lower mean doses to all OARs (except for maximum lung dose) compared to MIB-APBI. Conclusions: These results show that the use of DIBH significantly reduces cardiac doses in patients with left EBC. Partial irradiation techniques (PBI, MIB-APBI) significantly reduced cardiac doses due to the smaller clinical target volume. The best results were obtained with DIBH-PBI.

The global incidence of breast cancer is on the rise, a trend also observed in South Korea. However, thanks to the rapid advancements in anticancer therapies, survival rates are improving. Consequently, post-treatment health and quality of life for breast cancer survivors are emerging as significant concerns, particularly regarding treatment-related cardiotoxicity. In this review, we delve into the cardiovascular complications associated with breast cancer treatment, explore surveillance protocols for early detection and diagnosis of late complications, and discuss protective strategies against cardiotoxicity in breast cancer patients undergoing anticancer therapy, drawing from multiple guidelines.

Breast cancer is amongst the most common invasive cancers in adults. There are established relationships between anti-cancer treatments for breast cancer and cardiovascular side effects. In recent years, novel anti-cancer treatments have been established, as well as the availability of multi-modal cardiac imaging and the sophistication of treatment for cardiac disease. This review provides an in-depth overview regarding the interface of breast cancer and cancer therapy-related cardiovascular toxicity. Specifically, it reviews the pathophysiology of breast cancer, the method of action in therapy-related cardiovascular toxicity from anti-cancer treatment, the use of echocardiography, cardiac CT, MRI, or nuclear medicine as diagnostics, and the current evidence-based treatments available. It is intended to be an all-encompassing review for clinicians caring for patients in this situation.

Prolonged manned space flight exposure risks to galactic comic radiation, has led to uncertainties in a variety of health risks. Our previous work, utilizing either single ion or multiple ion radiation exposure conducted at the NSRL (NASA Space Radiation Laboratory, Brookhaven, NY) demonstrated that HZE ion components of the GCR result in persistent inflammatory signaling, increased mutations, and higher rates of cancer initiation and progression. With the development of the 33-beam galactic cosmic radiation simulations (GCRsim) at the NSRL, we can more closely test on earth the radiation environment found in space. With a previously used lung cancer susceptible mouse model (K-rasLA-1), we performed acute exposure experiments lasting 1-2 h, and chronic exposure experiments lasting 2-6 weeks with a total dose of 50 cGy and 75 cGy. We obtained histological samples from a subset of mice 100 days post-irradiation, and the remaining mice were monitored for overall survival up to 1-year post-irradiation. When we compared acute exposures (1-2 hrs.) and chronic exposure (2-6 weeks), we found a trend in the increase of lung adenocarcinoma respectively for a total dose of 50 cGy and 75 cGy. Furthermore, when we added neutron exposure to the 75 cGy of GCRsim, we saw a further increase in the incidence of adenocarcinoma. We interpret these findings to suggest that the risks of carcinogenesis are heightened with doses anticipated during a round trip to Mars, and this risk is magnified when coupled with extra neutron exposure that are expected on the Martian surface. We also observed that risks are reduced when the NASA official 33-beam GCR simulations are provided at high dose rates compared to low dose rates.

The effects of isolated contemporary low-dose breast cancer (BC) radiotherapy (RT) on the heart remain poorly understood. This study aims to assess the long-term impacts of BC-RT on cardiac structure and function.

Seventy-six women (62 ± 7 years) without history of prior heart disease, who had undergone RT for either first left (n = 36) or right (n = 40) BC, without additional medical oncology therapy apart from hormonal treatment 11 ± 1 years earlier, underwent transthoracic echocardiography, cardiac magnetic resonance imaging (CMR), computed tomography coronary angiography (CTCA), NT-proBNP, and a 6-min walk test (6MWT). They were compared with 54 age-matched healthy female controls. By CTCA, 68% of BC patients exhibited no or very mild coronary disease, while only 11% had moderate stenosis (50-69%) and 3% had significant stenosis (>70%). Despite slightly reduced regional echocardiographic midventricular strains, BC patients exhibited similar global left and right ventricular volumes, ejection fractions, and global strains by echocardiography and CMR as controls. Mitral E/e' ratios were slightly higher, and mitral deceleration times were slightly lower, but NT-proBNP was similar to controls. Also, 6MWT was normal. None had late gadolinium enhancement, and extracellular volume fraction was similar in BC (28 ± 3 vs. 29 ± 3, P = 0.15) and controls. No differences were observed relative to dose or side of RT.

Aside from minor alterations of regional strains and diastolic parameters, women who received isolated RT for BC had low prevalence of coronary disease, normal global systolic function, NT-proBNP, and exercise capacity and showed no structural changes by CMR, refuting significant long-term cardiotoxicity in such low-risk patients.

Doses to the coronary arteries in breast cancer (BC) radiotherapy (RT) have been suggested to be a risk predictor of long-term cardiac toxicity after BC treatment. We investigated the dose-risk relationships between near maximum doses (Dmax) to the right coronary artery (RCA) and left anterior descending coronary artery (LAD) and ischemic heart disease (IHD) mortality after BC RT.

In a cohort of 2,813 women diagnosed with BC between 1958 and 1992 with a follow-up of at least 10 years, we identified 134 cases of death due to IHD 10-19 years after BC diagnosis. For each case, one control was selected within the cohort matched for age at diagnosis. 3D-volume and 3D-dose reconstructions were obtained from individual RT charts. We estimated the Dmax to the RCA and the LAD and the mean heart dose (MHD). We performed conditional logistic regression analysis comparing piecewise spline transformation and simple linear modeling for best fit.

There was a linear dose-risk relationship for both the Dmax to the RCA (odds ratio [OR]/Gray [Gy] 1.03 [1.01-1.05]) and the LAD (OR/Gy 1.04 [1.02-1.06]) in a multivariable model. For MHD there was a linear dose-risk relationship (1,14 OR/Gy [1.08-1.19]. For all relationships, simple linear modelling was superior to spline transformations.

Doses to both the RCA and LAD are independent risk predictors of long-term cardiotoxicity after RT for BC In addition to the LAD, the RCA should be regarded as an organ at risk in RT planning.

To determine whether deep inspiratory breath-hold (DIBH) reduces dose to organs-at-risk (OAR), in particular the right coronary artery (RCA), in women with breast cancer requiring right-sided post-mastectomy radiotherapy (PMRT) including internal mammary chain (+IMC) radiotherapy (RT). Fourteen consecutive women requiring right-sided PMRT + IMC were retrospectively identified. Nodal delineation was in accordance with European Society for Radiology and Oncology (ESTRO) guidelines and tangential chest wall fields marked. Patients were planned with Anisotropic Analytical Algorithm using free-breathing (FB) and DIBH datasets. Dose was calculated using Acuros External Beam algorithm. FB and DIBH dose comparisons were analyzed for heart, RCA and right lung, as were chest wall and IMC planning target volumes (PTVs). DIBH vs FB resulted in median decreases of: the RCA mean dose by 0.6Gray (Gy) (interquartile range (IQR) 0.1, 1.9) (p = 0.002), RCA max dose by 1.8Gy (IQR 0.8, 6.1) (p = 0.002), and V5Gy by 2.9% (IQR 0.0, 37.2) (p = 0.016). RCA data indicated no statistically significant dosimetric reduction ≥10Gy. A median reduction of 1.7Gy (c -0.0, 7.1) (p = 0.019) in maximum heart dose was recorded with DIBH vs FB; no significant difference was observed in other heart and left anterior descending coronary artery parameters. The median reduction in right lung mean dose was 2.8Gy for DIBH vs FB plans (IQR 1.6, 3.6) (p = 0.001); significant median reductions of V5Gy, V20Gy, and V30Gy were all achieved with DIBH. Chest wall PTV coverage did not significantly differ between DIBH and FB plans; IMC dosimetric coverage improved with use of DIBH (V47.5Gy, V45Gy, V42Gy). DIBH reduced OAR dose in right-sided PMRT + IMC patients. A novel finding was that DIBH decreased RCA dose. Heart and right lung dose were also decreased with DIBH, whilst optimally dosed PTVs were maintained.

Statistically significant increases in ischemic heart disease (IHD) mortality with cumulative occupational external radiation dose were observed in the National Registry for Radiation Workers (NRRW) cohort. There were 174 541 subjects in the NRRW cohort. The start of follow up was 1955, and the end of the follow-up for each worker was chosen as the earliest date of death or emigration, their 85th birthday or 31 December 2011. The dose-response relationship showed a downward curvature at a higher dose level >0.4 Sv with the overall shape of the dose-response relationship best described by a linear-quadratic model. The smaller risk at dose >0.4 Sv appears to be primarily associated with workers who started employment at a younger age (<30 years old) and those who were employed for more than 30 years. We modelled the dose response by age-at-first exposure. For the age-at-first exposure of 30+ years old, a linear dose-response was the best fit. For age-at-first exposure <30 years old, there was no evidence of excess risk of IHD mortality for radiation doses below 0.1 Sv or above 0.4 Sv, excess risk was only observed for doses between 0.1-0.4 Sv. For this age-at-first exposure group, it was also found that the doses they received when they were less than 35 years old or greater than 50 years old did not contribute to any increased IHD risk.

It is an ongoing debate how much lung and heart irradiation impact overall survival (OS) after definitive radiotherapy for lung cancer. This study uses a large national cohort of patients with locally advanced NSCLC to investigate the association between OS and irradiation of lung and heart.

Treatment plans were acquired from six Danish radiotherapy centers, and patient characteristics were obtained from national registries. A hybrid segmentation tool automatically delineated the heart and substructures. Dose-volume histograms for all structures were extracted and analyzed using principal component analyses (PCAs). Parameter selection for a multivariable Cox model for OS prediction was performed using cross-validation based on bootstrapping.

The population consisted of 644 patients with a median survival of 26 months (95% confidence interval [CI]: 24-29). The cross-validation selected two PCA variables to be included in the multivariable model. PCA1 represented irradiation of the heart and affected OS negatively (hazard ratio, 1.14; 95% CI: 1.04-1.26). PCA2 characterized the left-right balance (right atrium and left ventricle) irradiation, showing better survival for tumors near the right side (hazard ratio, 0.92; 95% CI: 0.84-1.00). Besides the two PCA variables, the multivariable model included age, sex, body-mass index, performance status, tumor dose, and tumor volume.

Besides the classic noncardiac risk factors, lung and heart doses had a negative impact on survival, while it is suggested that the left side of the heart is a more radiation dose-sensitive region. The data indicate that overall heart irradiation should be reduced to improve the OS if possible.