A comparison of cardiovascular and pulmonary morbidities and risk factors in breast cancer survivors compared to an age-matched female control group in the Lifelines prospective population cohort.

PURPOSE: To provide more insight into late treatment-related toxicities among breast cancer (BC) survivors by comparing morbidities and risk factors between BC survivors and age-matched controls. MATERIALS AND METHODS: All female participants diagnosed with BC before inclusion in Lifelines, a population-based cohort in the Netherlands, were selected and matched 1:4 to female controls without any oncological history on birth year. Baseline was defined as the age at BC diagnosis. Outcomes were obtained from questionnaires and functional analyses performed at entry to Lifelines (follow-up 1; FU1) and several years later (FU2). Cardiovascular and pulmonary events were defined as morbidities that were absent at baseline but present at FU1 or FU2. RESULTS: The study consisted of 1,325 BC survivors and 5,300 controls. The median period from baseline (i.e., BC treatment) to FU1 and FU2 was 7 and 10 years, respectively. Among BC survivors more events of heart failure (OR: 1.72 [1.10-2.68]) and less events of hypertension (OR: 0.79 [0.66-0.94]) were observed. At FU2, more electrocardiographic abnormalities were found among BC survivors compared to controls (4.1% vs. 2.7%, respectively; p = 0.027) and Framingham scores for the 10-year risk of coronary heart disease were lower (difference: 0.37%; 95% CI [-0.70 to -0.03%]). At FU2, BC survivors had more frequently a forced vital capacity below the lower limit of normal than controls (5.4% vs. 2.9%, respectively; p = 0.040). CONCLUSION: BC survivors are at risk of late treatment-related toxicities despite a more favourable cardiovascular risk profile compared to age-matched female controls.

Automatic Cardiac Structure Contouring for Small Datasets with Cascaded Deep Learning Models.

Cardiac structure contouring is a time consuming and tedious manual activity used for radiotherapeutic dose toxicity planning. We developed an automatic cardiac structure segmentation pipeline for use in low-dose non-contrast planning CT based on deep learning algorithms for small datasets. Fifty CT scans were retrospectively selected and the whole heart, ventricles and atria were contoured. A two stage deep learning pipeline was trained on 41 non contrast planning CTs, tuned with 3 CT scans and validated on 6 CT scans. In the first stage, An InceptionResNetV2 network was used to identify the slices that contained cardiac structures. The second stage consisted of three deep learning models trained on the images containing cardiac structures to segment the structures. The three deep learning models predicted the segmentations/contours on axial, coronal and sagittal images and are combined to create the final prediction. The final accuracy of the pipeline was quantified on 6 volumes by calculating the Dice similarity coefficient (DC), 95% Hausdorff distance (95% HD) and volume ratios between predicted and ground truth volumes. Median DC and 95% HD of 0.96, 0.88, 0.92, 0.80 and 0.82, and 1.86, 2.98, 2.02, 6.16 and 6.46 were achieved for the whole heart, right and left ventricle, and right and left atria respectively. The median differences in volume were -4, -1, + 5, -16 and -20% for the whole heart, right and left ventricle, and right and left atria respectively. The automatic contouring pipeline achieves good results for whole heart and ventricles. Robust automatic contouring with deep learning methods seems viable for local centers with small datasets.

Qualitative Evaluation of Common Quantitative Metrics for Clinical Acceptance of Automatic Segmentation: a Case Study on Heart Contouring from CT Images by Deep Learning Algorithms.

Organs-at-risk contouring is time consuming and labour intensive. Automation by deep learning algorithms would decrease the workload of radiotherapists and technicians considerably. However, the variety of metrics used for the evaluation of deep learning algorithms make the results of many papers difficult to interpret and compare. In this paper, a qualitative evaluation is done on five established metrics to assess whether their values correlate with clinical usability. A total of 377 CT volumes with heart delineations were randomly selected for training and evaluation. A deep learning algorithm was used to predict the contours of the heart. A total of 101 CT slices from the validation set with the predicted contours were shown to three experienced radiologists. They examined each slice independently whether they would accept or adjust the prediction and if there were (small) mistakes. For each slice, the scores of this qualitative evaluation were then compared with the Sørensen-Dice coefficient (DC), the Hausdorff distance (HD), pixel-wise accuracy, sensitivity and precision. The statistical analysis of the qualitative evaluation and metrics showed a significant correlation. Of the slices with a DC over 0.96 (N = 20) or a 95% HD under 5 voxels (N = 25), no slices were rejected by the readers. Contours with lower DC or higher HD were seen in both rejected and accepted contours. Qualitative evaluation shows that it is difficult to use common quantification metrics as indicator for use in clinic. We might need to change the reporting of quantitative metrics to better reflect clinical acceptance.