Search

Purpose: To investigate whether the dose planned for cardiac structures is associated with the risk of heart disease (HD) in patients with breast cancer treated with radiation therapy, and whether this association is modified by the presence of coronary artery calcification (CAC).Methods and Materials: Radiation therapy planning computed tomographic (CT) scans and corresponding dose distribution maps of 5561 patients were collected, 5300 patients remained after the exclusion of ineligible patients and duplicates; 1899 patients received their CT scan before 2011, allowing long follow-up. CAC was detected automatically. Using an artificial intelligence-based method, the cardiac structures (heart, cardiac chambers, large arteries, 3 main coronary arteries) were segmented. The planned radiation dose to each structure separately and to the whole heart were determined. Patients were assigned to a low-, medium-, or high-dose group based on the dose to the respective heart structure. Information on HD hospitalization and mortality was obtained for each patient. The association of planned radiation dose to cardiac structures with risk of HD was investigated in patients with and without CAC using Cox proportional hazard analysis in the long follow-up population. Tests for interaction were performed.Results: After a median follow-up of 96.0 months (interquartile range, 84.2-110.4 months) in the long follow-up group, 135 patients were hospitalized for HD or died of HD. If the dose to a structure increased 1 Gy, the relative HD risk increased by 3% to 11%. The absolute increase in HD risk was substantially higher in patients with CAC (event-ratelow-dose = 14-15 vs event-ratehigh-dose = 15-34 per 1000 person-years) than in patients without CAC (event-ratelow-dose = 6-8 vs event-ratehigh-dose = 5-17 per 1000 person-years). No interaction between CAC and radiation dose was found.Conclusions: Radiation exposure of cardiac structures is associated with increased risk of HD. Automatic segmentation of cardiac structures enables spatially localized dose estimation, which can aid in the prevention of radiation therapy-induced cardiac damage. This could be especially valuable in patients with breast cancer and CAC.

Purpose: We describe a case in which a breast cancer patient with an implantable cardioverter-defibrillator (ICD) was treated with postmastectomy followed by axillary radiation therapy. The ICD was partly within the target volume and according to the treatment planning system would receive a maximum dose of about 36 Gy. Methods and Materials: Postoperatively, the patient had a wound infection needing surgical intervention and 3 months of antibiotics. Therefore, it was decided not to relocate the ICD but instead to switch off the shock function of the ICD for the entire radiation therapy course. Results: The ICD was successfully substituted with a wearable cardioverter defibrillator (WCD), which the patient wore during the 3-week radiation therapy period until 2 weeks after the end of treatment. The ICD function was monitored from the start of the treatment until 6 months after treatment. Conclusions: In situations in which an ICD needs to be switched off semipermanently, a WCD can be used as alternative. The patient in this report tolerated the WCD well. Despite the high dose received by the ICD, the device and its battery continued to function normally.

Purpose To evaluate and compare health-related quality of life (HRQL) of women with early-stage breast cancer (BC) treated with different radiotherapy (RT) regimens. Methods Data were collected from five prospective cohorts of BC patients treated with breast-conserving surgery and different RT regimens: intraoperative RT (IORT, 1 × 23.3 Gy; n = 267), external beam accelerated partial breast irradiation (EB-APBI, 10 × 3.85 Gy; n = 206), hypofractionated whole breast irradiation(hypo-WBI, 16 × 2.67 Gy; n = 375), hypo-WBI + boost(hypo-WBI-B, 21–26 × 2.67 Gy; n = 189), and simultaneous WBI + boost(WBI-B, 28 × 2.3 Gy; n = 475). Women ≥ 60 years with invasive/in situ carcinoma ≤ 30 mm, cN0 and pN0-1a were included. Validated EORTC QLQ-C30/BR23 questionnaires were used to asses HRQL. Multivariable linear regression models adjusted for confounding (age, comorbidity, pT, locoregional treatment, systemic therapy) were used to compare the impact of the RT regimens on HRQL at 12 and 24 months. Differences in HRQL over time (3–24 months) were evaluated using linear mixed models. Results There were no significant differences in HRQL at 12 months between groups except for breast symptoms which were better after IORT and EB-APBI compared to hypo-WBI at 12 months (p Conclusion In women with early-stage breast cancer, the radiotherapy regimen did not substantially influence long-term HRQL with the exception of breast symptoms. Breast symptoms are more common after WBI than after IORT or EB-APBI and improve slowly until no significant difference remains at 2 years posttreatment.

Contains fulltext : 235298.pdf (Publisher’s version ) (Open Access) Importance: Cardiovascular disease (CVD) is common in patients treated for breast cancer, especially in patients treated with systemic treatment and radiotherapy and in those with preexisting CVD risk factors. Coronary artery calcium (CAC), a strong independent CVD risk factor, can be automatically quantified on radiotherapy planning computed tomography (CT) scans and may help identify patients at increased CVD risk. Objective: To evaluate the association of CAC with CVD and coronary artery disease (CAD) in patients with breast cancer. Design, Setting, and Participants: In this multicenter cohort study of 15915 patients with breast cancer receiving radiotherapy between 2005 and 2016 who were followed until December 31, 2018, age, calendar year, and treatment-adjusted Cox proportional hazard models were used to evaluate the association of CAC with CVD and CAD. Exposures: Overall CAC scores were automatically extracted from planning CT scans using a deep learning algorithm. Patients were classified into Agatston risk categories (0, 1-10, 11-100, 101-399, >400 units). Main Outcomes and Measures: Occurrence of fatal and nonfatal CVD and CAD were obtained from national registries. Results: Of the 15915 participants included in this study, the mean (SD) age at CT scan was 59.0 (11.2; range, 22-95) years, and 15879 (99.8%) were women. Seventy percent (n = 11179) had no CAC. Coronary artery calcium scores of 1 to 10, 11 to 100, 101 to 400, and greater than 400 were present in 10.0% (n = 1584), 11.5% (n = 1825), 5.2% (n = 830), and 3.1% (n = 497) respectively. After a median follow-up of 51.2 months, CVD risks increased from 5.2% in patients with no CAC to 28.2% in patients with CAC scores higher than 400. After adjustment, CVD risk increased with higher CAC score (hazard ratio [HR]CAC = 1-10 = 1.1; 95% CI, 0.9-1.4; HRCAC = 11-100 = 1.8; 95% CI, 1.5-2.1; HRCAC = 101-400 = 2.1; 95% CI, 1.7-2.6; and HRCAC>400 = 3.4; 95% CI, 2.8-4.2). Coronary artery calcium was particularly strongly associated with CAD (HRCAC>400 = 7.8; 95% CI, 5.5-11.2). The association between CAC and CVD was strongest in patients treated with anthracyclines (HRCAC>400 = 5.8; 95% CI, 3.0-11.4) and patients who received a radiation boost (HRCAC>400 = 6.1; 95% CI, 3.8-9.7). Conclusions and Relevance: This cohort study found that coronary artery calcium on breast cancer radiotherapy planning CT scan results was associated with CVD, especially CAD. Automated CAC scoring on radiotherapy planning CT scans may be used as a fast and low-cost tool to identify patients with breast cancer at increased risk of CVD, allowing implementing CVD risk-mitigating strategies with the aim to reduce the risk of CVD burden after breast cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT03206333.

Background The onset of the COVID-19 pandemic forced the Dutch national screening program to a halt and increased the burden on health care services, necessitating the introduction of specific breast cancer treatment recommendations from week 12 of 2020. We aimed to investigate the impact of COVID-19 on the diagnosis, stage and initial treatment of breast cancer. Methods Women included in the Netherlands Cancer Registry and diagnosed during four periods in weeks 2–17 of 2020 were compared with reference data from 2018/2019 (averaged). Weekly incidence was calculated by age group and tumor stage. The number of women receiving initial treatment within 3 months of diagnosis was calculated by period, initial treatment, age, and stage. Initial treatment, stratified by tumor behavior (ductal carcinoma in situ [DCIS] or invasive), was analyzed by logistic regression and adjusted for age, socioeconomic status, stage, subtype, and region. Factors influencing time to treatment were analyzed by Cox regression. Results Incidence declined across all age groups and tumor stages (except stage IV) from 2018/2019 to 2020, particularly for DCIS and stage I disease (p wks2–8: 2.04, ORwks9–11: 2.18). Invasive tumors were less likely to be treated initially by mastectomy with immediate reconstruction (ORwks12–13: 0.52) or by breast conserving surgery (ORwks14–17: 0.75). Chemotherapy was less likely for tumors diagnosed in the beginning of the study period (ORwks9–11: 0.59, ORwks12–13: 0.66), but more likely for those diagnosed at the end (ORwks14–17: 1.31). Primary hormonal treatment was more common (ORwks2–8: 1.23, ORwks9–11: 1.92, ORwks12–13: 3.01). Only women diagnosed in weeks 2–8 of 2020 experienced treatment delays. Conclusion The incidence of breast cancer fell in early 2020, and treatment approaches adapted rapidly. Clarification is needed on how this has affected stage migration and outcomes.

Introduction The COVID-19 pandemic led to a significant drop in the incidence of cancer diagnoses in the Netherlands, partially due to the suspension of all national cancer screening programs on 16th March 2020 (week 12). Hospitals were forced to focus on care for COVID-19 patients resulting in limited capacity and down scaling of health care for non-COVID-19 patients. Specific recommendations for breast cancer treatment strategies, such as alterations in sequence, type, and/or frequency, were temporarily implemented from week 12 onwards. The aim of this study was to investigate the impact of the first outbreak on the initial treatment of breast cancer patients. Methods Women older than 18 years, treated within three months following their breast cancer diagnosis during weeks 2-17 2018-2019 (reference period) or weeks 2-17 2020 (COVID-19 period), were selected from the Netherlands Cancer Registry. Weeks 2-17 2020 were split up in four periods, based on the number of breast cancer diagnoses: weeks 2-8, weeks 9-11, weeks 12-13, and weeks 14-17. Average number of breast conserving surgeries (BCS), mastectomies with direct reconstruction (DR), mastectomies without DR, chemotherapy, endocrine therapy or other therapies, given as initial treatment per week, were calculated, stratified by period and by tumor stage. Treatments given to patients diagnosed in the reference period were compared with treatments given to patients diagnosed in the COVID-19 period, using a Mantel-Haenszel test, adjusting for age. Results A total of 16,553 patients were included in the current study. Of these patients 5,504 received their initial treatment in weeks 2-17 2018, 5,641 in weeks 2-17 2019 and 5,408 in weeks 2-17 2020. An increase in the use of endocrine therapy was seen in weeks 12-13 and 14-17 2020 compared to weeks 2-17 2018/2019, especially for patients with stage I cancer (12.3% and 7.7% vs 4.8%) and stage II cancer (25.4% and 17.4% vs 13.4%). In addition, a lower proportion of patients with stage II breast cancer received chemotherapy as first treatment in weeks 12-13 (21.1%) and 14-17 2020 (20.1%) compared to weeks 2-17 2018/2019 (29.8%) (Table). Discussion The COVID-19 pandemic led to a major increase in the use of endocrine therapy following the recommendations, which was mainly used to enable postponing surgery. The lower use of chemotherapy was probably related to the thought to limit hospital visits and the expected higher risk of developing COVID-19 complications due to chemotherapy. Possible long-term effects of changes in initial treatments will be monitored. Foodnote by table: Weeks 2-17 2020 (the COVID-19 period) were compared to the same weeks in 2018-2019, adjusted for age (74). A statistically significant: ↑ higher proportion of patients received this therapy, corrected for age; ↓ lower proportion of patients received this therapy, corrected for age; a: lower proportion of patients aged between 50 and 64 years received BCS; b: higher proportion of patients aged 39 or younger received mastectomy without DR; c: higher proportion of patients aged 39 or younger, or aged between 50 and 75 years received endocrine therapy; d: higher proportion of patients aged between 40 and 74 years received endocrine therapy; e: higher proportion of patients aged 74 or younger received endocrine therapy; f: higher proportion of patients aged 39 or younger received chemotherapy; g: higher proportion of patients aged 75 years or older received BCS Average number (percentage) initial treatments per week, stratified by stage and periodTotalBreast conserving surgeryMastectomy with direct reconstructionMastectomy without direct reconstructionChemotherapyEndocrine therapyTotalDCISWeek 2-17 2018/201940.629.5 (72.7)4.9 (12.0)5.7 (13.9)0.1 (0.2)0.3 (0.8)0.1 (0.2)Week 2-8 202043.730.9 (70.6)5.0 (11.4)7.3 (16.7)0.4 (1.0)0.1 (0.3)0.0 (0.0)Week 9-11 202038.027.0 (71.1)4.0 (10.5)7.0 (18.4)0.0 (0.0)0.0 (0.0)0.0 (0.0)Week 12-13 202048.031.5 (65.6)7.0 (14.6)7.0 (14.6)0.0 (0.0)2.5 (5.2) ↑0.0 (0.0)Week 14-17 202028.319.0 (67.3)3.0 (10.6)5.8 (20.4) ↑0.0 (0.0)0.5 (1.8)0.0 (0.0)Stage IWeek 2-17 2018/2019146.2104.5 (71.5)10.0 (6.8)17.8 (12.2)6.2 (4.3)7.0 (4.8)0.7 (0.5)Week 2-8 2020148.4107.9 (72.7)7.0 (4.7) ↓15.3 (10.3)10.0 (6.7) ↑7.4 (5.0)0.9 (0.6)Week 9-11 2020131.793.7 (71.1)8.0 (6.1)14.3 (10.9)6.3 (4.8)8.0 (6.1)1.3 (1.0)Week 12-13 2020163.0107.5 (66.0)a10.0 (6.1)20.0 (12.3)b4.5 (2.8)20.0 (12.3)c1.0 (0.6)Week 14-17 2020117.377.0 (65.7) ↓10.8 (9.2)16.8 (14.3)3.3 (2.8)9.0 (7.7) ↑0.5 (0.4)Stage IIWeek 2-17 2018/2019114.937.0 (32.2)5.0 (4.3)20.8 (18.1)34.3 (29.8)15.4 (13.4)2.5 (2.2)Week 2-8 2020116.133.4 (28.8) ↓4.1 (3.6)18.4 (15.9)38.4 (33.1) ↑18.3 (15.7)3.4 (3.0)Week 9-11 2020118.735.7 (30.1)5.7 (4.8)19.0 (16.0)36.0 (30.3)20.0 (16.9)2.3 (2.0)Week 12-13 2020142.042.5 (29.9)5.5 (3.9)26.5 (18.7)30.0 (21.1) ↓36.0 (25.4)d1.5 (1.1)Week 14-17 202083.327.5 (33.0)5.5 (6.6)16.0 (19.2)16.8 (20.1) ↓14.5 (17.4)e3.0 (3.6)Stage IIIWeek 2-17 2018/201931.12.0 (6.3)0.5 (1.7)5.8 (18.5)16.0 (51.5)5.3 (17.0)1.6 (5.0)Week 2-8 202027.92.4 (8.7)0.6 (2.1)5.0 (17.9)14.3 (51.3)4.7 (16.9)0.9 (3.1)Week 9-11 202026.72.0 (7.5)0.3 (1.3)5.7 (21.3)12.7 (47.5)f5.7 (21.3)0.3 (1.3)Week 12-13 202038.52.0 (5.2)0.5 (1.3)7.5 (19.5)19.0 (49.4)8.5 (22.1)1.0 (2.6)Week 14-17 202020.81.5 (7.2)1.3 (6.0) ↑4.5 (21.7)8.0 (38.6)4.5 (21.7)1.0 (4.8)Stage IVWeek 2-17 2018/201915.00.3 (2.3)0.0 (0.2)0.6 (4.0)5.3 (34.9)6.8 (44.9)2.1 (13.7)Week 2-8 202014.60.6 (3.9)0.0 (0.0)0.4 (2.9)4.7 (32.4)6.7 (46.1)2.1 (14.7)Week 9-11 202012.00.0 (0.0)0.0 (0.0)0.0 (0.0)3.3 (27.8)7.0 (58.3)1.3 (11.1)Week 12-13 202019.51.5 (7.7)0.0 (0.0)2.5 (12.8) ↑6.0 (30.8)7.5 (38.5)2.0 (10.3)Week 14-17 202013.80.3 (1.8)g0.0 (0.0)0.3 (1.8)3.8 (27.3)8.3 (60.0) ↑1.3 (9.1) Citation Format: Anouk H Eijkelboom, Linda de Munck, Marie-Jeanne Vrancken Peeters, Marjolein Smidt, Mireille Broeders, Monique Bos, Marjanka K Schmidt, Maud Bessems, Luc Strobbe, Desirée van den Bongard, Aafke Honkoop, Janneke Verloop, Cristina Guerrero Paez, Marc Lobbes, Sabine Linn, Pieter Westenend, Catharina W Menke-van der Houven van Oordt, Jelle Wesseling, Vivianne Tjan Heijnen, Sabine Siesling, On behalve of the NABON COVID-19 consortium. Effect of the COVID-19 pandemic on the initial treatment of breast cancer in the Netherlands: A population-based study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-88.

Background and Objective: The Trials within Cohorts design aims to reduce recruitment difficulties and disappointment bias in pragmatic trials. On cohort enrollment, broad informed consent for randomization is asked, after which cohort participants can be randomized to interventions or serve as controls without further notification. We evaluated patients' recollection, understanding, and acceptance of broad consent in a clinical oncology setting. Methods: We surveyed 610 patients with cancer participating in ongoing TwiCs; 482 patients (79%) responded, of which 312 patients shortly after cohort enrollment, 108 patients after randomization to an intervention (12-18 months after cohort enrollment), and a random sample of 62 cohort participants who had not been selected for interventions (1-6 months after cohort enrollment). Results: Shortly after providing cohort consent, 76% of patients (238/312) adequately remembered whether they had given broad consent for randomization. Of patients randomly offered interventions, 76% (82/108) remembered giving broad consent for randomization; 41% (44/108) understood they were randomly selected, 44% (48/108) were not interested in selection procedures, and 10% (11/108) did not understand selection was random. Among patients not selected for interventions, 42% (26/62) understood selection was random; 89% felt neutral regarding the scenario of "not being selected for an intervention while your data were being used in comparison with patients receiving interventions,"10% felt reassured (6/62) and 2% scared/insecure (2/62). Conclusion: Patients adequately remember giving broad consent for randomization shortly after cohort enrollment and after being offered an intervention, but recollection is lower in those never selected for interventions. Patients are acceptant of serving as control without further notifications. (c) 2020 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Purpose To evaluate symptoms of late radiation toxicity, side effects, and quality of life in breast cancer patients treated with hyperbaric oxygen therapy (HBOT). Methods For this cohort study breast cancer patients treated with HBOT in 5 Dutch facilities were eligible for inclusion. Breast cancer patients with late radiation toxicity treated with ≥ 20 HBOT sessions from 2015 to 2019 were included. Breast and arm symptoms, pain, and quality of life were assessed by means of the EORTC QLQ-C30 and -BR23 before, immediately after, and 3 months after HBOT on a scale of 0–100. Determinants associated with persistent breast pain after HBOT were assessed. Results 1005/1280 patients were included for analysis. Pain scores decreased significantly from 43.4 before HBOT to 29.7 after 3 months (p p p n = 576, 57.3%) and mild barotrauma (n = 179, 17.8%). Moderate/severe side effects were reported in 3.2% (n = 32) of the patients. Active smoking during HBOT and shorter time (i.e., median 17.5 vs. 22.0 months) since radiotherapy were associated with persistent breast pain after HBOT. Conclusion Breast cancer patients with late radiation toxicity reported reduced pain, breast and arm symptoms, and improved quality of life following treatment with HBOT.

Purpose The Trials within Cohorts (TwiCs) design aims to overcome problems faced in conventional RCTs. We evaluated the TwiCs design when estimating the effect of exercise on quality of life (QoL) and fatigue in inactive breast cancer survivors. Methods UMBRELLA Fit was conducted within the prospective UMBRELLA breast cancer cohort. Patients provided consent for future randomization at cohort entry. We randomized inactive patients 12–18 months after cohort enrollment. The intervention group (n = 130) was offered a 12-week supervised exercise intervention. The control group (n = 130) was not informed and received usual care. Six-month exercise effects on QoL and fatigue as measured in the cohort were analyzed with intention-to-treat (ITT), instrumental variable (IV), and propensity scores (PS) analyses. Results Fifty-two percent (n = 68) of inactive patients accepted the intervention. Physical activity increased in patients in the intervention group, but not in the control group. We found no benefit of exercise for dimensions of QoL (ITT difference global QoL: 0.8, 95% CI = − 2.2; 3.8) and fatigue, except for a small beneficial effect on physical fatigue (ITT difference: − 1.1, 95% CI = − 1.8; − 0.3; IV: − 1.9, 95% CI = − 3.3; − 0.5, PS: − 1.2, 95% CI = − 2.3; − 0.2). Conclusion TwiCs gave insight into exercise intervention acceptance: about half of inactive breast cancer survivors accepted the offer and increased physical activity levels. The offer resulted in no improvement on QoL, and a small beneficial effect on physical fatigue. Trial registration Netherlands Trial Register (NTR5482/NL.52062.041.15), date of registration: December 07, 2015.

BACKGROUND: Although several deep learning (DL) calcium scoring methods have achieved excellent performance for specific CT protocols, their performance in a range of CT examination types is unknown. PURPOSE: To evaluate the performance of a DL method for automatic calcium scoring across a wide range of CT examination types and to investigate whether the method can adapt to different types of CT examinations when representative images are added to the existing training data set. MATERIALS AND METHODS: The study included 7240 participants who underwent various types of nonenhanced CT examinations that included the heart: coronary artery calcium (CAC) scoring CT, diagnostic CT of the chest, PET attenuation correction CT, radiation therapy treatment planning CT, CAC screening CT, and low-dose CT of the chest. CAC and thoracic aorta calcification (TAC) were quantified using a convolutional neural network trained with (a) 1181 low-dose chest CT examinations (baseline), (b) a small set of examinations of the respective type supplemented to the baseline (data specific), and (c) a combination of examinations of all available types (combined). Supplemental training sets contained 199–568 CT images depending on the calcium burden of each population. The DL algorithm performance was evaluated with intraclass correlation coefficients (ICCs) between DL and manual (Agatston) CAC and (volume) TAC scoring and with linearly weighted κ values for cardiovascular risk categories (Agatston score; cardiovascular disease risk categories: 0, 1–10, 11–100, 101–400, >400). RESULTS: At baseline, the DL algorithm yielded ICCs of 0.79–0.97 for CAC and 0.66–0.98 for TAC across the range of different types of CT examinations. ICCs improved to 0.84–0.99 (CAC) and 0.92–0.99 (TAC) for CT protocol–specific training and to 0.85–0.99 (CAC) and 0.96–0.99 (TAC) for combined training. For assignment of cardiovascular disease risk category, the κ value for all test CT scans was 0.90 (95% confidence interval [CI]: 0.89, 0.91) for the baseline training. It increased to 0.92 (95% CI: 0.91, 0.93) for both data-specific and combined training. CONCLUSION: A deep learning calcium scoring algorithm for quantification of coronary and thoracic calcium was robust, despite substantial differences in CT protocol and variations in subject population. Augmenting the algorithm training with CT protocol–specific images further improved algorithm performance. © RSNA, 2020 See also the editorial by Vannier in this issue.

Objectives: This study evaluates the risk of cardiovascular disease (CVD) following breast cancer, accounting for baseline CVD risk. Methods: Within the EPIC-NL (Dutch part of the European Prospective Investigation into Nutrition and Cancer) cohort, 1103 women were diagnosed with breast cancer. For every breast cancer patient, 3–4 women without breast cancer (n = 4328) were selected matched for age, year, and time since cohort enrollment. Based on CVD risk factors at cohort enrollment, 10-year risk of CVD was calculated and categorized: low ( 20%). Cox proportional hazard models assessed the risk of CVD events (hospitalization or mortality) and CVD mortality of women with versus without breast cancer, adjusted for baseline CVD risk. Results: After median follow-up of 5 and 6 years, 92 (8.3%) and 325 (7.5%) CVD events occurred in women with and without breast cancer, respectively. In the low CVD risk group, women with breast cancer had 1.44 (95% CI 1.00–2.06) times higher risk of CVD events than women without breast cancer. In the intermediate and high CVD risk categories, risk of CVD events was similar in women with and without breast cancer. Overall, women with breast cancer had 1.77 (95% CI 1.10–2.86) times higher risk of CVD mortality than women without breast cancer. Conclusions: Among women with low CVD risk, women with breast cancer have a higher risk of CVD event than women without breast cancer. Overall, women with breast cancer have a higher risk of CVD mortality than women without breast cancer.

Background: Following breast-conserving surgery and post-operative 3D-conformal accelerated partial breast irradiation (APBI), suboptimal cosmetic results have been reported. Preoperative radiation delivery to the intact tumor enables better target visualization and treatment volume reduction. Single dose preoperative APBI has the potential to improve toxicity profiles, reduce treatment burden and enable in vivo exploration of breast cancer radiogenomics. Purpose: Develop practical guidelines for single dose external beam preoperative APBI. Methods: Recommended dose constraints were derived from pooled dosimetry estimates from 2 clinical trials. In an American dose escalation trial, a uniform 15, 18 or 21 Gy dose has previously been evaluated for non-lobular cT1N0 or low/intermediate grade DCIS

Purpose Stereotactic body radiation therapy (SBRT) has become a widely adopted treatment for patients with oligometastatic disease, despite limited evidence of superiority. We compared pain response and quality of life (QoL) in patients with oligometastatic disease treated with conventionally fractionated 3-dimensional radiation therapy (3DCRT) or SBRT to bone metastases. Methods and Materials We included patients with oligometastatic disease (≤5 lesions within ≤3 organs) treated within the prospective PRESENT cohort. Main outcomes were pain response, clinical local control, and QoL 2, 4, and 8 weeks and 3, 6, and 12 months after treatment. Pain response was assessed only in patients who reported pain at baseline and was defined according to international consensus criteria. Results Of 131 patients with oligometastatic disease, 66 patients were treated with 3DCRT and 65 patients with SBRT. A pain response was achieved in 81% (3DCRT) versus 84% (SBRT) with a median duration of 23 weeks (range, 1-58) and 24 weeks (range, 0-50), respectively. Reirradiation was needed in 33% versus 5% of the patients, respectively. None of the QoL subscales were significantly different between both groups. Conclusions In patients with oligometastatic disease, SBRT to bone metastases did not improve pain response or QoL compared with 3DCRT. Reirradiation was less often needed in the SBRT group.

Purpose In this multicenter phase 2 feasibility study, we investigated the impact of preoperative accelerated partial breast irradiation (PAPBI) on local control, breast fibrosis, and cosmetic outcome. Methods and Materials Women aged >60 years with an invasive, unifocal (mammography and magnetic resonance imaging), nonlobular adenocarcinoma of the breast were treated with PAPBI. Six weeks after radiation therapy, a wide local excision was performed. Radiation therapy consisted of 10 × 4 Gy (2010-2013) or 5 × 6 Gy (after 2013) to the tumor (gross target volume) with a 25 mm margin (20 mm from gross target volume to clinical target volume, 5 mm planning target volume). Results One hundred thirty-three patients treated between 2010 and 2016 were analyzed with a median follow-up of 5.0 years (0.9-8.8 years). Seventy-eight (59%) patients were treated with 10 × 4 Gy in 2 weeks and 55 (41%) patients with 5 × 6 Gy in 1 week. Eighteen postoperative complications (14%) occurred in 15 patients (11%). The proportion of patients with no to mild fibrosis in the treated part of the breast at 2 years and later time points was around 90%. Cosmesis improved over time in several patients: excellent to good cosmetic score as rated by the physician was 68% at 6 months and 92% at 5 years. Seventy-seven percent (6 months) to 82% (5 years) of patients were “satisfied” or “very satisfied” with their cosmetic outcome. Three recurrences were detected in the biopsy track and 1 recurrence in the ipsilateral breast. Conclusions PAPBI is a feasible method with a low postoperative complication rate, limited fibrosis, and good to excellent cosmetic outcome. The local recurrence rate was 3% at 5 years; however, no local recurrences were observed since removal of the needle biopsy track.

Background: Lymphedema of the breast/chest wall after breast cancer treatment is often associated with pain and reduced quality of life. We conducted a pilot study to evaluate whether the use of a compression vest reduced symptoms of breast/chest wall edema in breast cancer patients. Methods and Results: This single-center study included patients (n = 25) with symptomatic breast/chest wall edema with a pain score of ≥3 on the Numerical Rating Scales (range 1-10). The patients were instructed to wear a compression vest (Lymphatrex, Class II) for 6 months. Wilcoxon signed-rank tests were used to compare differences in patient-reported pain intensity/severity. Analyses included all patients with available data. In total, 17 (68%) continued to wear their vests for 6 months, whereas the other 8 withdrew prematurely. At baseline, median pain severity (4.9, interquartile range [IQR] 3.6-6.0) and pain interference (4.3, IQR 2.1-5.9) scores were significantly higher compared with pain scores after wearing the compression vest for 6 months (1.8 IQR 1.0-4.8 and 1.4 IQR 0.9-4.4, resp.). Patient-reported breast/chest wall swelling decreased from 92% (n = 22) at baseline to 71% (n = 12) at 6 months. The prevalence of moderate/severe patient-reported breast/chest wall pain declined from 63% (n = 15) at baseline to 18% (n = 3) at 6 months. Physical, emotional, and social functioning improved over time and was comparable to scores of the Dutch reference population. Conclusion: The results of this pilot study suggest that a compression vest could be an acceptable and effective treatment option for patients with painful breast/chest wall edema. In compliant patients, swelling and pain was significantly reduced.

Background The association between lymphedema of the arm and impaired health-related QoL (HR-QoL) has led to changes in clinical practice. However, data on lymphedema of the breast (ie, breast edema) are lacking. We prospectively evaluated patient-reported prevalence and determinants of breast edema and its effect on patient-reported HR-QoL and breast pain. Methods We prospectively included 836 patients undergoing breast-conserving surgery followed by radiotherapy between October 2013 and October 2016 (UMBRELLA cohort). Patient-reported breast edema, HR-QoL, and breast pain were assessed by means of European Organisation for Research and Treatment of Cancer-C30/BR23 before starting radiotherapy and at 3, 6, 12, and 18 months thereafter. We assessed which patient, tumor, and treatment characteristics were associated with breast edema. With mixed-effects models, we assessed the impact of breast edema on patient-reported HR-QoL domains and breast pain over time, adjusting for confounders. Results Within a median follow-up of 28 months (interquartile range [IQR] = 15), 207 (24.8%) patients reported breast edema at some point in time. Prevalence of breast edema was highest at 6 months (12.4%, 95% confidence interval [CI] = 10.0 to 14.7). Larger tumor size, oncoplastic surgery, axillary lymph node dissection, locoregional radiotherapy, radiotherapy boost on the tumor bed, and adjuvant chemotherapy were associated with breast edema. Breast edema was independently associated with more breast pain and with poorer QoL, physical functioning, and body image. Conclusions Breast edema occurs frequently within the first year after breast-conserving surgery and radiotherapy and is independently associated with impaired HR-QoL and more breast pain. This information is important for use in clinical practice and should be discussed with patients during shared decision making.

ObjectivesTo investigate trends in cardiovascular disease (CVD) risk following breast cancer using national registry data.MethodsA nationwide cohort study was conducted, comprising 163 881 women with in situ (7.6%) or invasive (92.4%) breast cancer and women of the general population, ranging from 3 661 141 in 1996 to 4 566 573 in 2010. CVD mortality rate in women with and without breast cancer and hospitalisation rate after breast cancer were calculated for the years 1996–2010. Age-adjusted CVD and breast cancer mortality within 5 years after breast cancer admission (1997–2010) were compared with 1996 calculated with a Cox proportional hazard analysis.ResultsThe absolute 10-year CVD mortality risk following breast cancer decreased from 56 per 1000 women in 1996 to 41 in 2005 (relative reduction=27.8%). In the general population, this decreased from 73 per 1000 women in 1996 to 55 in 2005 (–23.9%). The absolute risk of CVD hospitalisation within 1 year following breast cancer increased from 54 per 1000 women in 1996 to 67 in 2009 (+23.6%), which was largely explained by an increase in hospitalisation for hypertension, pulmonary embolism, rheumatoid heart/valve disease and heart failure. The 5-year CVD mortality risk was 42% lower (HR 0.58, 95% CI=0.48 to 0.70) for women admitted for breast cancer in 2010 compared with 1996.ConclusionsCVD mortality risk decreased in women with breast cancer and in women of the general population, with women with breast cancer having a lower risk of CVD mortality. By contrast, there was an increase in hospitalisation for CVD in women with breast cancer.

Purpose: This study automatically quantified calcifications in coronary arteries (CAC) and thoracic aorta (TAC) on breast planning computed tomography (CT) scans and assessed its reproducibility compared to manual scoring. Material and Methods: Dutch (n = 1199) and Singaporean (n = 1090) breast cancer patients with radiotherapy planning CT scan were included. CAC and TAC were automatically scored using deep learning algorithm. CVD risk categories were based on Agatson CAC: 0, 1–10, 11–100, 101–400 and >400. Reliability between automatic and manual scoring was assessed in 120 randomly selected CT scans from each population, with linearly weighted kappa for CAC categories and intraclass correlation coefficient for TAC. Results: Median age was higher in Dutch patients than Singaporean patients: 57 versus 52 years. CAC and TAC increased with age and were more present in Dutch patients than Singaporean patients: 24.2% versus 17.3% and 73.0% versus 62.2%, respectively. Reliability of CAC categories and TAC was excellent in the Netherlands (0.85 (95% confidence interval (CI) = 0.77–0.93) and 0.98 (95% CI = 0.96–0.98) respectively) and Singapore (0.90 (95% CI = 0.84–0.96) and 0.99 (95% CI = 0.98–0.99) respectively). Conclusions: CAC and TAC prevalence was considerable and increased with age. Deep learning software is a reliable method to automatically measure CAC and TAC on radiotherapy breast CT scans.

Background and purpose A radiosurgical treatment approach for early-stage breast cancer has the potential to minimize the patient's treatment burden. The dosimetric feasibility for single fraction ablative radiotherapy was evaluated by comparing volumetric modulated arc therapy (VMAT) with an interstitial multicatheter brachytherapy (IMB) approach. Methods and materials The tumors of 20 patients with early-stage breast cancer were delineated on a preoperative contrast-enhanced planning CT-scan, co-registered with a contrast-enhanced magnetic resonance imaging (MRI), both in radiotherapy supine position. A dose of 15Gy was prescribed to the planned target volume of the clinical target volume (PTV CTV ), and 20Gy integrated boost to the PTV of the gross tumor volume (PTV GTV ). Treatment plans for IMB and VMAT were optimized for adequate target volume coverage and minimal organs at risk (OAR) dose. Results The median PTV GTV/CTV receiving at least 95% of the prescribed dose was ⩾99% with both techniques. The median PTV CTV unintentionally receiving 95% of the prescribed PTV GTV dose was 65.4% and 4.3% with IMB and VMAT, respectively. OAR doses were comparable with both techniques. Conclusion MRI-guided single fraction radiotherapy with an integrated ablative boost to the GTV is dosimetrically feasible with both techniques. We perceive IMB less suitable for clinical implementation due to PTV CTV overdosage. Future studies have to confirm the clinical feasibility of the single fraction ablative approach.

Background and purpose The aim of this study is to assess the toxicity and cosmetic outcome of preoperative accelerated partial breast irradiation (PAPBI) for breast cancer patients with low risk on local recurrence. Material and methods Women aged ⩾60years with an invasive, unifocal ⩽3cm on MRI, (non-lobular) adenocarcinoma of the breast and a negative sentinel node received PAPBI (40Gray in 10 fractions over 2weeks). Six weeks after radiotherapy a wide local excision was performed. Results 70 patients with a median follow-up of 23months (3–44months) were evaluated. The overall postoperative infection rate was 11%. At 1, 2 and 3years of follow-up respectively 89%, 98% and 100% of patients had no or mild induration-fibrosis. Fibrosis was only found in a small volume of the breast. The global cosmetic outcome was good to excellent in 77% at 6months to 100% at 3years. Two patients developed a local recurrence. Conclusion Our first results show limited fibrosis in a small volume and good to excellent cosmetic outcome. In selected patients, preoperative radiotherapy appears to be a good option for breast conserving therapy.

Purpose To evaluate the toxicity and efficacy of the combination of external beam radiation therapy (EBRT) followed by high-dose-rate endorectal brachytherapy (HDREBT) boost in elderly and medically inoperable patients with rectal cancer. Methods and Materials A phase 1 dose-escalation study was performed. Treatment consisted of EBRT (13 × 3 Gy) followed by 3 weekly brachytherapy applications 6 weeks later. The HDREBT dose started at 5 Gy per fraction, increasing with 1 Gy per fraction if dose-limiting toxicity (DLT, defined as grade ≥3 proctitis

Background Noninvasive or minimally invasive treatments are being developed as alternatives to surgery for patients with early-stage breast cancer. Patients' preferences with regard to these new treatments have not been investigated. Objectives To assess preferences of patients with breast cancer and of healthy women regarding these new techniques, compared with conventional surgical treatments. Methods Six hypothetical breast cancer treatment-outcome scenarios were developed: three standard surgical scenarios (mastectomy, mastectomy with immediate implant-based reconstruction, and breast-conserving therapy [BCT]) and three minimally invasive or noninvasive scenarios (radiofrequency ablation, magnetic resonance-guided high-intensity focused ultrasound ablation, and single-dose ablative radiotherapy). Participants rated treatment-outcome scenarios by visual analogue scale (VAS) and time trade-off (TTO). The Friedman and post hoc Wilcoxon signed-rank tests were used to test whether scores were significantly different from BCT. Results Seventy-one patients with breast cancer and 50 healthy volunteers participated. Overall, BCT was rated the highest in terms of VAS (0.80) and TTO (0.90) scores. After stratification, BCT ranked the highest in most subgroups, with the exception of healthy individuals, who had given the highest score to ablative boost (VAS, 0.80; TTO, 0.88). Mastectomy with immediate reconstruction was the least preferred in most subgroups. Conclusions This study showed no significant preference for minimally invasive treatment for breast cancer. Using hypothetical scenarios, breast cancer survivors attributed the highest scores to BCT, whereas healthy volunteers showed a slight preference for minimally invasive treatments.

Objectives: The Trials within Cohorts (TwiCs) design is an alternative for pragmatic randomized controlled trials (RCTs) and might overcome disadvantages such as difficult recruitment, dropout after randomization to control, and contamination. We investigated the applicability of the TwiCs design in an exercise oncology study regarding the recruitment process, representativeness of the study sample, contamination, participation, and dropout.Methods: The Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaLuAtion (UMBRELLA) Fit TwiCs evaluates an exercise intervention in inactive breast cancer patients. Eligible patients participating in the prospective UMBRELLA were identified and randomized. Patients randomized to the intervention (n = 130) were offered the intervention, whereas controls (n = 130) were not informed.Results: Fifty-two percent (n = 68) accepted the intervention. Because this rate was lower than expected, a larger sample size was required than initially estimated (n = 166). However, recruitment of 260 patients was still completed by one researcher within 30 months. Unselective eligibility screening and randomization before invitation improved representativeness. Disadvantage of the design might be inclusion of ineligible patients when cohort information is limited. Furthermore, the design faced higher noncompliance in the intervention group, but prevention of contamination.Conclusion: The TwiCs design improved logistics in recruitment and prevented contamination, but noncompliance due to refusal of the intervention was higher compared with conventional pragmatic exercise oncology RCTs, which may dilute the estimated intervention effect. (C) 2019 The Authors. Published by Elsevier Inc.

Purpose To reduce arm morbidity, routine axillary lymph node dissection (ALND) is often omitted or replaced by axillary radiotherapy (AxRT) in patients with limited nodal involvement. We evaluated patient-reported arm morbidity and physical functioning in breast cancer patients undergoing modern-day axillary treatment. Methods All patients within the UMBRELLA cohort undergoing local radiotherapy with sentinel lymph node biopsy (SLNB), ALND and/or AxRT were selected. Patient-reported arm morbidity and physical functioning were assessed with EORTC QLQ C30/BR23 questionnaires up to eighteen months after initiation of radiotherapy. Patient-reported outcomes were compared between patients with SLNB only, ALND only, AxRT (level I–II), AxRT (level I–IV) or AxRT plus ALND by means of mixed model analysis. Results In total, 949 patients were identified; 641 (68%) SLNB only, 57 (6%) ALND only, 94 (10%) AxRT level I–II, 72 (8%) AxRT level I–IV and 85 (9%) ALND + AxRT. SLNB only resulted in the least arm morbidity scores. ALND + AxRT resulted in most arm morbidity, with clinically relevant differences at 18 months. AxRT (level I–II or level I–IV) resulted in significantly less arm symptoms in the first 3 months compared to ALND. Arm symptom scores between those receiving AxRT on levels I–II and I–IV were similar. Conclusion Of all axillary management strategies, ALND plus AxRT is associated with worst patient-reported outcomes. AxRT resulted in less arm morbidity compared to ALND. Selective radiotherapy treatment of the axilla, i.e. radiotherapy of levels I–II only instead of levels I–IV, did not lead to clinically relevant reduced arm morbidity.

Background: Health apps are increasingly being used in clinical care and may hold significant theoretical potential. However, they are often implemented in clinical care before any research has been done to confirm actual benefits for patients, physicians, and researchers. Objective: This study aimed to explore experiences of patients and health care providers with the use of a supportive breast cancer app during the first 6 months following diagnosis, in terms of benefits for clinical practice and research purposes. Methods: Between June 2013 and April 2014, breast cancer patients of all ages were invited shortly after diagnosis to use a supportive breast cancer app, and were followed for 6 months. Patients were asked to use the app at their own convenience. In-depth interviews were conducted regularly with patients and their medical team (ie, physicians and nurses) to evaluate their experiences. Results: A total of 15 patients aged 30-63 years participated. The medical team consisted of 7 physicians and 3 specialized breast cancer nurses. Out of the 15 patients, 12 (80%) used the app to obtain information on breast cancer and treatment. A total of 11 out of 12 patients (92%) evaluated this information as useful. All 15 patients used the app to record consultations with practitioners, and 14 (93%) found this useful. Symptom registration was used by 8 out of 15 patients (53%), and was found useful by 4 out of these 8 patients (50%). Overall, 14 out of 15 patients (93%) would recommend the app to other patients. The app, in particular the recording function, was rated as useful by 9 out of 10 medical professionals (90%), and they reported that it did not increase consultation time. These 9 professionals would recommend the app to their patients. Conclusions: This evaluation of a supportive health app shows positive experiences among patients and their medical teams. Based on experiences in this study, patients may need to be actively encouraged to regularly register symptoms within health apps to generate sufficient patient-reported app data for use in clinical practice and scientific research. [JMIR Cancer 2016;2(1):e8]

For breast boost radiotherapy or accelerated partial breast irradiation, the tumor bed (TB) is delineated by the radiation oncologist on a planning computed tomography (CT) scan. The aim of the present study was to investigate whether the interobserver variability (IOV) of the TB delineation is reduced by providing the radiation oncologist with additional magnetic resonance imaging (MRI) or CT scans. A total of 14 T1-T2 breast cancer patients underwent a standard planning CT in the supine treatment position following lumpectomy, as well as additional pre-and postoperative imaging in the same position. Post-lumpectomy TBs were independently delineated by four breast radiation oncologists on standard postoperative CT and on CT registered to an additional imaging modality. The additional imaging modalities used were postoperative MRI, preoperative contrast-enhanced (CE)-CT and preoperative CE-MRI. A cavity visualization score (CVS) was assigned to each standard postoperative CT by each observer. In addition, the conformity index (CI), volume and distance between centers of mass (dCOM) of the TB delineations were calculated. On CT, the median CI was 0.57, with a median volume of 22 cm3 and dCOM of 5.1 mm. The addition of postoperative MRI increased the median TB volume significantly to 28 cm3 (P3, respectively (both P

OBJECTIVES: Coronary artery calcium (CAC) is a strong and independent predictor of cardiovascular disease (CVD) risk. This study assesses reproducibility of automatic CAC scoring on radiotherapy planning computed tomography (CT) scans of breast cancer patients, and examines its association with traditional cardiovascular risk factors. METHODS: This study included 561 breast cancer patients undergoing radiotherapy between 2013 and 2015. CAC was automatically scored with an algorithm using supervised pattern recognition, expressed as Agatston scores and categorized into five categories (0, 1-10, 11-100, 101-400, >400). Reproducibility between automatic and manual expert scoring was assessed in 79 patients with automatically determined CAC above zero and 84 randomly selected patients without automatically determined CAC. Interscan reproducibility of automatic scoring was assessed in 294 patients having received two scans (82% on the same day). Association between CAC and CVD risk factors was assessed in 36 patients with CAC scores >100, 72 randomly selected patients with scores 1-100, and 72 randomly selected patients without CAC. Reliability was assessed with linearly weighted kappa and agreement with proportional agreement. RESULTS: 134 out of 561 (24%) patients had a CAC score above zero. Reliability of CVD risk categorization between automatic and manual scoring was 0.80 (95% Confidence Interval (CI): 0.74-0.87), and slightly higher for scans with breath-hold. Agreement was 0.79 (95% CI: 0.72-0.85). Interscan reliability was 0.61 (95% CI: 0.50-0.72) with an agreement of 0.84 (95% CI: 0.80-0.89). Ten out of 36 (27.8%) patients with CAC scores above 100 did not have other cardiovascular risk factors. CONCLUSIONS: Automatic CAC scoring on radiotherapy planning CT scans is a reliable method to assess CVD risk based on Agatston scores. One in four breast cancer patients planned for radiotherapy have elevated CAC score. One in three patients with high CAC scores don't have other CVD risk factors and wouldn't have been identified as high risk.