Supine MRI for regional breast radiotherapy: Imaging axillary lymph nodes before and after sentinel-node biopsy

Regional radiotherapy (RT) is increasingly used in breast cancer treatment. Conventionally, computed tomography (CT) is performed for RT planning. Lymph node (LN) target levels are delineated according to anatomical boundaries. Magnetic resonance imaging (MRI) could enable individual LN delineation. The purpose was to evaluate the applicability of MRI for LN detection in supine treatment position, before and after sentinel-node biopsy (SNB). Twenty-three female breast cancer patients (cTis-3N0M0) underwent 1.5 T MRI, before and after SNB, in addition to CT. Endurance for MRI was monitored. Axillary levels were delineated. LNs were identified and delineated on MRI from before and after SNB, and on CT, and compared by Wilcoxon signed-rank tests. LN locations and LN-based volumes were related to axillary delineations and associated volumes. Although postoperative effects were visible, LN numbers on postoperative MRI (median 26 LNs) were highly reproducible compared to preoperative MRI when adding excised sentinel nodes, and higher than on CT (median 11, p < 0.001). LN-based volumes were considerably smaller than respective axillary levels. Supine MRI of LNs is feasible and reproducible before and after SNB. This may lead to more accurate RT target definition compared to CT, with potentially lower toxicity. With the MRI techniques described here, initiation of novel MRI-guided RT strategies aiming at individual LNs could be possible

The use of a wearable cardioverter defibrillator during postmastectomy radiotherapy as an alternative for relocation of the pulse generator

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

MR-guided breast radiotherapy: Feasibility and magnetic-field impact on skin dose

The UMC Utrecht MRI/linac (MRL) design provides image guidance with high soft-tissue contrast, directly during radiotherapy (RT). Breast cancer patients are a potential group to benefit from better guidance in the MRL. However, due to the electron return effect, the skin dose can be increased in presence of a magnetic field. Since large skin areas are generally involved in breast RT, the purpose of this study is to investigate the effects on the skin dose, for whole-breast irradiation (WBI) and accelerated partial-breast irradiation (APBI). In ten patients with early-stage breast cancer, targets and organs at risk (OARs) were delineated on postoperative CT scans co-registered with MRI. The OARs included the skin, comprising the first 5 mm of ipsilateral-breast tissue, plus extensions. Three intensity-modulated RT techniques were considered (2× WBI, 1× APBI). Individual beam geometries were used for all patients. Specially developed MRL treatment-planning software was used. Acceptable plans were generated for 0 T, 0.35 T and 1.5 T, using a class solution. The skin dose was augmented in WBI in the presence of a magnetic field, which is a potential drawback, whereas in APBI the induced effects were negligible. This opens possibilities for developing MR-guided partial-breast treatments in the MRL. © 2013 Institute of Physics and Engineering in Medicine

Patient Preferences for Minimally Invasive and Open Locoregional Treatment for Early-Stage Breast Cancer

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

Development and validation of a method to determine the unbound paclitaxel fraction in human plasma

Paclitaxel is pharmaceutically formulated in a mixture of Cremophor EL and ethanol (1:1, v/v). The unbound fraction of the anticancer drug paclitaxel in plasma is dependent on both plasma protein binding and entrapment in Cremophor EL micelles. We have developed a simple and reproducible method for the quantification of the unbound paclitaxel fraction in human plasma. Human plasma was spiked with [3H]paclitaxel and [14C]glucose (unbound reference) and incubated at 37 degrees C for 30 min. Plasma ultrafiltrate was prepared by a micropartition system (MPS-1) and collected in a sample cup containing 100 microl of plasma to prevent the loss of paclitaxel due to adsorption. The radionuclides were separated after combustion of the biological samples using a sample oxidizer and the radioactivity was determined by liquid scintillation counting. The unbound fraction of paclitaxel was calculated by dividing the ratios of 3H and 14C in plasma ultrafiltrate and in plasma. The method was thoroughly validated using human plasma spiked with pharmacologically relevant concentrations of paclitaxel (10-1000 ng/ml) and Cremophor EL (0.25-2.0%). The method was precise, with a within-day precision ranging from 3.9 to 11.0% and a between-day precision ranging from 5.8 to 13.1%. In patient plasma with low serum albumin values containing 1% of Cremophor EL, the unbound fraction appeared to be significantly higher than that in plasma with normal albumin values. The determination of the unbound fraction of paclitaxel proved to be stable during a 10-week storage at -20 degrees C. Furthermore, the assay was applicable in patient samples. This assay can be used to determine the unbound fraction of paclitaxel in plasma. Moreover, its design should allow the determination of the unbound concentrations of other hydrophobic drug

Intrafraction motion during radiotherapy of breast tumor, breast tumor bed, and individual axillary lymph nodes on cine magnetic resonance imaging

Background and purpose: In (ultra-)hypofractionation, the contribution of intrafraction motion to treatment accuracy becomes increasingly important. Our purpose was to evaluate intrafraction motion and resulting geometric uncertainties for breast tumor (bed) and individual axillary lymph nodes, and to compare prone and supine position for the breast tumor (bed). Materials and methods: During 1–3 min of free breathing, we acquired transverse/sagittal interleaved 1.5 T cine magnetic resonance imaging (MRI) of the breast tumor (bed) in prone and supine position and coronal/sagittal cine MRI of individual axillary lymph nodes in supine position. A total of 31 prone and 23 supine breast cine MRI (in 23 women) and 52 lymph node cine MRI (in 24 women) were included. Maximum displacement, breathing amplitude, and drift were analyzed using deformable image registration. Geometric uncertainties were calculated for all displacements and for breathing motion only. Results: Median maximum displacements (range over the three orthogonal orientations) were 1.1–1.5 mm for the breast tumor (bed) in prone and 1.8–3.0 mm in supine position, and 2.2–2.4 mm for lymph nodes. Maximum displacements were significantly smaller in prone than in supine position, mainly due to smaller breathing amplitude: 0.6–0.9 mm in prone vs. 0.9–1.4 mm in supine. Systematic and random uncertainties were 0.1–0.4 mm in prone position and 0.2–0.8 mm in supine position for the tumor (bed), and 0.4–0.6 mm for the lymph nodes. Conclusion: Intrafraction motion of breast tumor (bed) and individual lymph nodes was small. Motion of the tumor (bed) was smaller in prone than in supine position

Patient Preferences for Minimally Invasive and Open Locoregional Treatment for Early-Stage Breast Cancer

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

Quantification of intra-fraction motion in breast radiotherapy using supine magnetic resonance imaging

In early-stage breast-cancer patients, accelerated partial-breast irradiation techniques (APBI) and hypofractionation are increasingly implemented after breast-conserving surgery (BCS). For a safe and effective radiation therapy (RT), the influence of intra-fraction motion during dose delivery becomes more important as associated fraction durations increase and targets become smaller. Current image-guidance techniques are insufficient to characterize local target movement in high temporal and spatial resolution for extended durations. Magnetic resonance imaging (MRI) can provide high soft-tissue contrast, allow fast imaging, and acquire images during longer periods. The goal of this study was to quantify intra-fraction motion using MRI scans from 21 breast-cancer patients, before and after BCS, in supine RT position, on two time scales. High-temporal 2-dimensional (2D) MRI scans (cine-MRI), acquired every 0.3 s during 2 min, and three 3D MRI scans, acquired over 20 min, were performed. The tumor (bed) and whole breast were delineated on 3D scans and delineations were transferred to the cine-MRI series. Consecutive scans were rigidly registered and delineations were transformed accordingly. Motion in sub-second time-scale (derived from cine-MRI) was generally regular and limited to a median of 2 mm. Infrequently, large deviations were observed, induced by deep inspiration, but these were temporary. Movement on multi-minute scale (derived from 3D MRI) varied more, although medians were restricted to 2.2 mm or lower. Large whole-body displacements (up to 14 mm over 19 min) were sparsely observed. The impact of motion on standard RT techniques is likely small. However, in novel hypofractionated APBI techniques, whole-body shifts may affect adequate RT delivery, given the increasing fraction durations and smaller targets. Motion management may thus be required. For this, on-line MRI guidance could be provided by a hybrid MRI/RT modality, such as the University Medical Center Utrecht MRI linear accelerator