The Importance of Radiation Dose to the Atherosclerotic Plaque in the Left Anterior Descending Coronary Artery for Radiation-Induced Cardiac Toxicity of Breast Cancer Patients?

IMPORTANCE: Radiation-induced acute coronary events (ACEs) may occur as treatment-related late side effect of breast cancer (BC) radiation. However, the underlying mechanisms behind this radiation-induced cardiac disease remains to be determined. OBJECTIVE: The objective of this study was to test the hypothesis that radiation dose to calcified atherosclerotic plaques in the left anterior descending coronary artery (LAD) is a better predictor for ACEs than radiation dose to the whole heart or left ventricle in BC patients treated with radiotherapy (RT). DESIGN, SETTING, PARTICIPANTS, AND MAIN OUTCOMES AND MEASURES: The study cohort consisted of 910 BC patients treated with postoperative RT after breast conserving surgery. In total, 163 patients had an atherosclerotic plaque in the LAD. The endpoint was the occurrence of an ACE after treatment. For each individual patient, the mean heart dose (MHD), volume of the left ventricle receiving ≥ 5 Gy (LV-V5), mean LAD dose and mean dose to calcified atherosclerotic plaques in the LAD, if present, were acquired based on planning CT-scans. Cox-regression analysis was used to analyse the effects on the cumulative incidence of ACEs. RESULTS: The median follow-up time was 9.2 years (range: 0.1-14.3 years). In total, 38 patients (4.2%) developed an ACE during follow-up. For patients with an atherosclerotic plaque (n=163) the mean dose to the atherosclerotic plaque was the strongest predictor for ACE, even after correction for cardiovascular risk factors (HR: 1.269 (95% CI: 1.090-1.477), P=0.002). The LV-V5 was associated with ACEs in patients without atherosclerotic plaques in the LAD (n=680) (hazard ratio (HR): 1.021 (95% CI: 1.003-1.039; P=0.023). CONCLUSION AND RELEVANCE: The results of this study suggest that radiation dose to pre-existing calcified atherosclerotic plaques in the LAD is strongly associated with the development of ACEs in BC patients

Association Between Cardiac Radiation Exposure and the Risk of Arrhythmia in Breast Cancer Patients Treated With Radiotherapy:A Case-Control Study

Background: Previous studies suggested that radiation therapy (RT) for breast cancer (BC) can induce cardiac arrhythmias and conduction disorders. However, the association with mean heart dose and specific cardiac substructures doses was less studied. Materials and Methods: We conducted a nested case-control study based on French BC patients, enrolled in the European MEDIRAD-BRACE study (https://clinicaltrials.gov, Identifier: NCT03211442), who underwent three-dimensional conformal radiation therapy (3D-CRT) between 2009 and 2013 and were retrospectively followed until 2019. Cases were incident cases of cardiac arrhythmia. Controls without arrhythmia were selected with propensity-scored matching by age, duration of follow-up, chemotherapy, hypertension, and diabetes (ratio 1:4 or 5). Doses to the whole heart (WH), left and right atria (LA and RA), and left and right ventricles (LV and RV) were obtained after delineation with multi-atlas-based automatic segmentation. Results: The study included 116 patients (21 cases and 95 controls). Mean age at RT was 64 ± 10 years, mean follow-up was 7.0 ± 1.3 years, and mean interval from RT to arrhythmia was 4.3 ± 2.1 years. None of the results on association between arrhythmia and cardiac doses reached statistical significance. However, the proportion of right-sided BC was higher among patients with arrhythmia than among controls (57% vs. 51%, OR = 1.18, p = 0.73). Neither mean WH dose, nor LV, RV, and LA doses were associated with an increased risk of arrhythmia (OR = 1.00, p > 0.90). In contrast, the RA dose was slightly higher for cases compared to controls [interquartile range (0.61-1.46 Gy) vs. (0.49-1.31 Gy), p = 0.44], and a non-significant trend toward a potentially higher risk of arrhythmia with increasing RA dose was observed (OR = 1.19, p = 0.60). Subanalysis according to BC laterality showed that the association with RA dose was reinforced specifically for left-sided BC (OR = 1.76, p = 0.75), while for right-sided BC, the ratio of mean RA/WH doses may better predict arrhythmia (OR = 2.39, p = 0.35). Conclusion: Despite non-significant results, our exploratory investigation on BC patients treated with RT is the first study to suggest that right-sided BC patients and the right atrium irradiation may require special attention regarding the risk of cardiac arrhythmia and conduction disorders. Further studies are needed to expand on this topic

Validation of separate multi-atlases for auto segmentation of cardiac substructures in CT-scans acquired in deep inspiration breath hold and free breathing

Background and purpose: Developing NTCP-models for cardiac complications after breast cancer (BC) radiotherapy requires cardiac dose-volume parameters for many patients. These can be obtained by using multi-atlas based automatic segmentation (MABAS) of cardiac structures in planning CT scans. We investigated the relevance of separate multi-atlases for deep inspiration breath hold (DIBH) and free breathing (FB) CT scans. Materials and methods: BC patients scanned in DIBH (n = 10) and in FB (n = 20) were selected to create separate multi-atlases consisting of expert panel delineations of the whole heart, atria and ventricles. The accuracy of atlas-generated contours was validated with expert delineations in independent datasets (n = 10 for DIBH and FB) and reported as Dice coefficients, contour distances and dose-volume differences in relation to interobserver variability of manual contours. Dependency of MABAS contouring accuracy on breathing technique was assessed by validation of a FB atlas in DIBH patients and vice versa (cross validation). Results: For all structures the FB and DIBH atlases resulted in Dice coefficients with their respective reference contours > 0.8 and average contour distances < 2 mm smaller than slice thickness of (CTs). No significant differences were found for dose-volume parameters in volumes receiving relevant dose levels (WH, LV and RV). Accuracy of the DIBH atlas was at least similar to, and for the ventricles better than, the interobserver variation in manual delineation. Cross-validation between breathing techniques showed a reduced MABAS performance. Conclusion: Multi-atlas accuracy was at least similar to interobserver delineation variation. Separate atlases for scans made in DIBH and FB could benefit atlas performance because accuracy depends on breathing technique

Histological assessment of gonads in DSD: relevance for clinical management

Malignant gonadal germ cell tumors, referred to as germ cell cancers (GCC), occur with increased frequency in individuals who have specific types of differences (disorders) of sex development (DSD). Recent population-based studies have identified new environmental and genetic risk factors that have led to a 'genvironment' hypothesis, which may potentially be helpful in risk assessment in DSD-related GCC. In DSD, the malignancy risk is highly heterogeneous, but recent studies allow now to discriminate between high- and low-risk conditions. Gonadal biopsy is in some cases the best procedure of choice to assess the risk, and with the availability of immunohistochemical biomarkers [OCT3/4 (POU5F1), TSPY, SOX9, FOXL2 and KITLG (SCF)], a reliable classification of GCC and its precursors can be made. The opportunities in the field of virtual diagnostic pathology will be presented, having possibilities for rare diseases in general and DSD specifically. It is expected that the International DSD Registry will stimulate international collaborations, facilitating better diagnostic procedures as well as research

Impact of the COVID-19 pandemic on patients with hepatocellular carcinoma in the west of Scotland: a cohort study

Objective: The COVID-19 pandemic had an undoubted impact on the provision of elective and emergency cancer care, including the diagnosis and management of patients with hepatocellular carcinoma (HCC). Our aim was to determine the effects of the COVID-19 pandemic on patients with HCC in the West of Scotland. Design: This was a retrospective audit of a prospectively collated database of patients presented to the West of Scotland Multidisciplinary Team (MDT) between April and October 2020 (during the pandemic), comparing baseline demographics, characteristics of disease at presentation, diagnostic workup, treatment and outcomes with patients from April to October 2019 (pre pandemic). Results: There was a 36.5% reduction in new cases referred to the MDT during the pandemic. Patients presented at a significantly later Barcelona Cancer Liver Clinic stage (24% stage D during the pandemic, 9.5% pre pandemic, p&lt;0.001) and with a significantly higher Child-Pugh Score (46% Child-Pugh B/C during the pandemic vs 27% pre pandemic, p&lt;0.001). We observed a reduction in overall survival (OS) among all patients with a median OS during the pandemic of 6 months versus 17 months pre pandemic (p=0.048). Conclusion: The impact of the COVID-19 pandemic is likely to have contributed to a reduction in the presentation of new cases and survival among patients with HCC in the West of Scotland. The reason for this is likely multifactorial, but disruption of standard care is likely to have played a significant role. Resources should be provided to address the backlog and ensure there are robust investigation and management pathways going forward

Impact of the COVID-19 pandemic on patients with hepatocellular carcinoma in the West of Scotland: a cohort study

Objective The COVID-19 pandemic had an undoubted impact on the provision of elective and emergency cancer care, including the diagnosis and management of patients with hepatocellular carcinoma (HCC). Our aim was to determine the effects of the COVID-19 pandemic on patients with HCC in the West of Scotland.Design This was a retrospective audit of a prospectively collated database of patients presented to the West of Scotland Multidisciplinary Team (MDT) between April and October 2020 (during the pandemic), comparing baseline demographics, characteristics of disease at presentation, diagnostic workup, treatment and outcomes with patients from April to October 2019 (pre pandemic).Results There was a 36.5% reduction in new cases referred to the MDT during the pandemic. Patients presented at a significantly later Barcelona Cancer Liver Clinic stage (24% stage D during the pandemic, 9.5% pre pandemic, p&lt;0.001) and with a significantly higher Child-Pugh Score (46% Child-Pugh B/C during the pandemic vs 27% pre pandemic, p&lt;0.001). We observed a reduction in overall survival (OS) among all patients with a median OS during the pandemic of 6 months versus 17 months pre pandemic (p=0.048).Conclusion The impact of the COVID-19 pandemic is likely to have contributed to a reduction in the presentation of new cases and survival among patients with HCC in the West of Scotland. The reason for this is likely multifactorial, but disruption of standard care is likely to have played a significant role. Resources should be provided to address the backlog and ensure there are robust investigation and management pathways going forward