D. Van den Bongard

Abstract P3-12-23: Breast and chest wall edema during and following radiotherapy in breast cancer patients: Prevalence, risk factors and quality of life

PURPOSE/OBJECTIVE Innovations in loco-regional breast cancer treatment, such as oncoplastic surgery and neoadjuvant chemotherapy, have been suggested to increase the risk of breast and chest wall edema, which may impair quality of life (QoL) during and after treatment. The objective of this study is to evaluate prevalence and risk factors of breast and chest wall edema and its effect on quality of life. METHODS We conducted this study within a prospective observational cohort of breast cancer patients indicated to undergo radiation treatment after being treated with surgery (Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaluation, UMBRELLA). At the time of inclusion all participants consented to the collection of clinical data and 9patient reported outcomes9 (PROMs) at regular intervals during and after treatment. Presence of breast and chest wall edema was registered by radiation oncologists according to CTCAE V4.0 scoring system, at weekly follow-up visits during radiation treatment, and at standard follow-up intervals after radiation treatment. When present, edema was defined as 9acute9 (i.e. breast and chest wall edema within 0-90 days after the start of radiation treatment), 9late9 (i.e. >90 days) or both. Information on potential risk factors, such as patient and tumor characteristics, and treatment (e.g. surgical procedure, RT target volumes, (neo)adjuvant chemotherapy) was collected from electronic patient files and questionnaires. We performed univariate and multivariable logistic regression analysis to identify determinants that were (independently) associated with breast and chest wall edema. PROMs on quality of life and pain (i.e. EORTC QLQ-C30/BR23) were collected regularly (i.e. baseline, 3, 6 and 12 months) and compared between patients with and without edema. RESULTS We included 427 patients with at least 3 months follow-up (median follow-up 48 weeks). Sixteen percent (70/427) had acute edema, 23% (73/314) had late edema and 8% (25/314) had both acute and late edema. The proportion of women with acute edema was significantly higher in patients treated with oncoplastic surgery (31% vs. 15%, p=0.03) or mastectomy (31% vs. 14% p CONCLUSION Breast and chest wall edema is associated with reduced quality of life during the first year of treatment. Oncoplastic surgery and mastectomy increase the risk for acute edema, while oncoplastic surgery, mastectomy, axillary treatment (i.e. ALND, radiation therapy) and the presence of acute edema are associated with late edema. Early treatment of acute edema may reduce the risk for late edema, prolonged pain and impaired quality of life. Citation Format: Young-Afat DA, Verkooijen HM, Gregorowitsch ML, van Gils CH, van der Pol CC, Witkamp AJ, Burgmans I, Jonasse Y, van Vulpen M, van den Bongard DJ. Breast and chest wall edema during and following radiotherapy in breast cancer patients: Prevalence, risk factors and quality of life. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-12-23.

Abstract P5-18-02: The cohort multiple randomized controlled trial is a feasible and patient-acceptable design for pragmatic evaluation of multiple interventions, with potential for improved recruitment and generalisability: The UMBRELLA experience

Introduction: The randomized controlled trial (RCT) is the gold standard for evaluation of effectiveness of new interventions. In oncology, however, RCTs are often complicated by logistic challenges, slow recruitment, limited generalisability, and strong patient9s and doctor9s preferences for new interventions. At the University Medical Center Utrecht (the Netherlands), we implemented an innovative alternative to the classic RCT: the cohort multiple randomized controlled trial (cmRCT). The cmRCT serves as a multi-trial facility and has the potential to improve recruitment and generalisability. Methods: We initiated the 9Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaluation (UMBRELLA)9 at the department of radiation oncology. UMBRELLA is a large prospective cohort of breast cancer patients, for whom we capture clinical data (patient and tumor characteristics, treatment, imaging, toxicity, recurrence and survival). Patients provide Patient Reported Outcome Measures (PROMs) on quality of life, pain, fatigue, anxiety and depression, physical activity and cosmetics. For each intervention to be tested, a subcohort of eligible patients is identified within UMBRELLA. From this subcohort, a random sample of patients is selected and offered the intervention (which they can accept or refuse). Patients from the subcohort, who are not randomly selected, receive standard care, serve as controls, and are not informed about the trial. Outcomes of patients offered the intervention are compared to those of patients receiving standard care. This process can be repeated (simultaneously) for multiple experimental interventions. Results: Since October 2013, some 1000 patients have been enrolled in UMBRELLA. In order to make the design suitable for the clinical oncology practice, we developed a tailored informed consent procedure. First, we ask patients to enroll in the cohort and to provide PROMs. In addition, patients give broad consent to be either randomly selected to receive experimental interventions or to serve as control without further notice. In a second stage, at the initiation of a trial within the cohort, informed consent to receive the experimental intervention is sought in those randomly selected to receive the intervention. After completion of the trial, aggregated results are shared with all patients. Participation in UMBRELLA is 90%, and 90% of enrolled patients give broad consent for randomization. PROMs return rates vary from 70-90%. In September 2015, the first trial will be initiated, which aims to evaluate the impact of exercise programs on quality of life of inactive survivors. Preliminary inclusion and participation rates of this trial will be presented in December. Conclusion: High participation rates, high PROM return rates and high levels of broad informed consent for randomisation within UMBRELLA indicate that this innovative design is feasible in the oncology practice, acceptable for patients and likely to provide generalisable results. Results of trials within UMBRELLA need to confirm whether cmRCT is indeed an acceptable alternative for classic pragmatic RCTs. Citation Format: Verkooijen HM, Young Afat D, van den Bongard D, van Vulpen M, May AM, van Gils C. The cohort multiple randomized controlled trial is a feasible and patient-acceptable design for pragmatic evaluation of multiple interventions, with potential for improved recruitment and generalisability: The UMBRELLA experience. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-18-02.

Abstract P4-11-12: Quality of life, anxiety and depression during treatment of ductal carcinoma in situ and invasive breast cancer

INTRODUCTION Patients with ductal carcinoma in situ (DCIS) have excellent overall survival rates. Yet, previous studies suggested that quality of life (QoL) between patients with DCIS and patients with early-invasive breast cancer (early-IBC) are similar after treatment. We compared anxiety, depression and quality of life of patients with DCIS and patients with early-IBC during treatment, at the initiation of postsurgical radiotherapy. METHODS We conducted this study within a prospective observational cohort of breast cancer patients indicated to receive adjuvant radiation treatment at the department of Radiation Oncology at the University Medical Center Utrecht, the Netherlands (9the UMBRELLA cohort9). At the time of inclusion all cohort participants consented to the collection of clinical and patient reported outcomes (PROMs) at regular intervals. Patient reported outcomes on QoL (i.e. EORTC QLQ-C30) and anxiety and depression (i.e. HADS) were collected at the start of postsurgical radiotherapy. All patients who were diagnosed between October 2013 and January 2015 with DCIS or early-IBC (i.e. pT1 and pT2 without lymph node involvement) were included in this analysis. To analyze differences in mean levels of PROMs (i.e. anxiety and depression, QoL) between patients with DCIS and early-IBC, two sample t-tests were used. Differences in proportions of patients with high anxiety or high depressive scores (i.e. scores ≥11) were analyzed with the Pearson-Chi square test. We compared PROMS of DCIS and early-IBC patients with those of patients with advanced-invasive breast cancer from the UMBRELLA cohort using analyses of variance (ANOVA). RESULTS Forty-six patients were diagnosed with DCIS and 227 with early-IBC. DCIS and early-IBC patients did not show statistically significant differences in levels of anxiety (mean DCIS 4.5, early-IBC 5.2, p=0.18), depression (mean DCIS 2.6, early-IBC 3.0, p=0.73) or QoL (mean DCIS 78.3, early-IBC 74.7 p=0.70). Seven percent of women with DCIS women reported severe anxious symptoms, compared to 8% in women with early-IBC (p=0.22). Severe symptoms of depression were seen in 2% of DCIS patients and 4% of early-IBC (p=0.30). Patients with advanced invasive breast cancer (n=118) reported significantly higher anxiety (mean 6.3, p CONCLUSION Despite excellent survival probabilities and less invasive treatment, women with DCIS report similar levels of anxiety, depression and quality of life during treatment as compared to women with early-invasive breast cancer. Citation Format: Young-Afat DA, Gregorowitsch ML, Pignol J-P, van Gils CH, van Vulpen M, van den Bongard DJ, Verkooijen HM. Quality of life, anxiety and depression during treatment of ductal carcinoma in situ and invasive breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-11-12.

SU-C-17A-05: Quantification of Intra-Fraction Motion of Breast Tumors Using Cine-MRI

PURPOSE Magnetic resonance imaging (MRI) enables direct characterization of intra-fraction motion ofbreast tumors, due to high softtissue contrast and geometric accuracy. The purpose is to analyzethis motion in early-stage breast-cancer patients using pre-operative supine cine-MRI. METHODS MRI was performed in 12 female early-stage breast-cancer patients on a 1.5-T Ingenia (Philips)wide-bore scanner in supine radiotherapy (RT) position, prior to breast-conserving surgery. Twotwodimensional (2D) T2-weighted balanced fast-field echo (cine-MRI) sequences were added tothe RT protocol, oriented through the tumor. They were alternately acquired in the transverse andsagittal planes, every 0.3 s during 1 min. A radiation oncologist delineated gross target volumes(GTVs) on 3D contrast-enhanced MRI. Clinical target volumes (CTV = GTV + 15 mm isotropic)were generated and transferred onto the fifth time-slice of the time-series, to which subsequents lices were registered using a non-rigid Bspline algorithm; delineations were transformed accordingly. To evaluate intra-fraction CTV motion, deformation fields between the transformed delineations were derived to acquire the distance ensuring 95% surface coverage during scanning(P95%), for all in-plane directions: anteriorposterior (AP), left-right (LR), and caudal-cranial(CC). Information on LR was derived from transverse scans, CC from sagittal scans, AP fromboth sets. RESULTS Time-series with registration errors - induced by motion artifacts - were excluded by visual inspection. For our analysis, 11 transverse, and 8 sagittal time-series were taken into account. Themedian P95% calculated in AP (19 series), CC (8), and LR (11) was 1.8 mm (range: 0.9-4.8), 1.7mm (0.8-3.6), and 1.0 mm (0.6-3.5), respectively. CONCLUSION Intra-fraction motion analysis of breast tumors was achieved using cine-MRI. These first results show that in supine RT position, motion amplitudes are limited. This information can be used for adaptive RT planning, and to develop preoperative partial-breast RT strategies, such asablative RT for early-stage breast-cancer patients.

TH-A-BRF-05: MRI of Individual Lymph Nodes to Guide Regional Breast Radiotherapy

PURPOSE In regional radiotherapy (RT) for breast-cancer patients, direct visualization of individual lymph nodes (LNs) may reduce target volumes and Result in lower toxicity (i.e. reduced radiation pneumonitis, arm edema, arm morbidity), relative to standard CT-based delineations. To this end, newly designed magnetic resonance imaging (MRI) sequences were optimized and assessed qualitatively and quantitatively. METHODS In ten healthy female volunteers, a scanning protocol was developed and optimized. Coronal images were acquired in supine RT position positioned on a wedge board on a 1.5 T Ingenia (Philips) wide-bore MRI. In four volunteers the optimized MRI protocol was applied, including a 3-dimensional (3D) T1-weighted (T1w) fast-field-echo (FFE). T2w sequences, including 3D FFE, 3D and 2D fast spin echo (FSE), and diffusion-weighted single-shot echo-planar imaging (DWI) were also performed. Several fatsuppression techniques were used. Qualitative evaluation parameters included LN contrast, motion susceptibility, visibility of anatomical structures, and fat suppression. The number of visible axillary and supraclavicular LNs was also determined. RESULTS T1 FFE, insensitive to motion, lacked contrast of LNs, which often blended in with soft tissue and blood. T2 FFE showed high contrast, but some LNs were obscured due to motion. Both 2D and 3D FSE were motion-insensitive having high contrast, although some blood remained visible. 2D FSE showed more anatomical details, while in 3D FSE, some blurring occurred. DWI showed high LN contrast, but suffered from geometric distortions and low resolution. Fat suppression by mDixon was the most reliable in regions with magnetic-field inhomogeneities. The FSE sequences showed the highest sensitivity for LN detection. CONCLUSION MRI of regional LNs was achieved in volunteers. The FSE techniques were robust and the most sensitive. Our optimized MRI sequences can facilitate direct delineation of individual LNs. This can Result in smaller target volumes and reduced toxicity in regional RT compared to standard CT planning.