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Purpose: We report on a dosimetrical study of three patient positions (supine, prone dive, and prone crawl) and four irradiation techniques for whole-breast irradiation (WBI): wedged-tangential fields (W-TF), tangential-field intensity-modulated radiotherapy (TF-IMRT), multi-beam IMRT (MB-IMRT), and intensity-modulated arc therapy (IMAT). This is the first study to evaluate prone crawl positioning in WBI and the first study to quantify dosimetrical and anatomical differences with prone dive positioning., Methods: We analyzed five datasets with left- and right-sided patients (n = 51). One dataset also included deep-inspiration breath hold (DIBH) data. A total of 252 new treatment plans were composed. Dose-volume parameters and indices of conformity were calculated for the planning target volume (PTV) and organs-at-risk (OARs). Furthermore, anatomical differences among patient positions were quantified to explain dosimetrical differences., Results: Target coverage was inferior for W-TF and supine position. W-TF proved overall inferior, and IMAT proved foremost effective in supine position. TF-IMRT proved competitive to the more demanding MB-IMRT and IMAT in prone dive, but not in prone crawl position. The lung-sparing effect was overall confirmed for both prone dive and prone crawl positioning and was largest for prone crawl. For the heart, no differences were found between prone dive and supine positioning, whereas prone crawl showed cardiac advantages, although minor compared to the established heart-sparing effect of DIBH. Dose differences for contralateral breast were minor among the patient positions. In prone crawl position, the ipsilateral breast sags deeper and the PTV is further away from the OARs than in prone dive position., Conclusions: The prone dive and prone crawl position are valid alternatives to the supine position in WBI, with largest advantages for lung structures. For the heart, differences are small, which establishes the role of DIBH in different patient positions. These results may be of particular interest to radiotherapy centers with limited technical resources., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Purpose: Prone whole breast irradiation results in lower dose to organs at risk compared with supine position, especially lung dose. However, the adoption of prone position for whole breast irradiation + lymph node irradiation remains limited and data on lymph node irradiation in 5 fractions are lacking. Although the study was ended prematurely for the primary endpoint (breast retraction at 2 years), we decided to report acute toxicity for prone and supine positions and 5 and 15 fractions. Additionally, dosimetry and set-up accuracy between prone and supine positions were evaluated., Methods and Materials: A randomized open-label factorial 2 × 2 design was used for an acute toxicity comparison between prone and supine positions and 5 and 15 fractions. The primary endpoint of the trial was breast retraction 2 years after treatment. In total, 57 patients were evaluated. Dosimetry and set-up errors were compared between prone and supine positions. All patients were positioned on either our in -house developed prone crawl breast couch or a Posirest-2 (Civco)., Results: No difference in acute toxicity between prone and supine positions was found, but 5 fractions did result in a lower risk of desquamation (15% vs 41%; P = .04). Prone positioning resulted in lower mean ipsilateral lung dose (2.89 vs 4.89 Gy; P < .001), mean thyroid dose (3.42 vs 6.61 Gy; P = .004), and mean contralateral breast dose (0.41 vs 0.54 Gy; P = .007). No significant difference in mean heart dose (0.90 vs 1.07 Gy; P = .22) was found. Set-up accuracy was similar between both positions., Conclusions: Unfortunately, the primary endpoint of the trial was not met due to premature closure of the trial. Acceleration in 5 fractions resulted in a lower risk of desquamation. Prone positioning did not influence acute toxicity or set-up accuracy, but did result in lower ipsilateral mean lung dose, thyroid dose, and contralateral breast dose., (Copyright © 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

In whole breast and regional nodal irradiation (WB + RNI), breathhold increases organ at risk (OAR) sparing. WB + RNI is usually performed in supine position, because positioning materials obstruct beam paths in prone position. Recent advancements allow prone WB + RNI (pWB + RNI) with increased sparing of OARs compared to supine WB + RNI. We evaluate positional and dosimetrical impact of repeated breathhold (RBH) and failure to breathhold (FTBH) in pWB + RNI. Twenty left-sided breast cancer patients were scanned twice in breathhold (baseline and RBH) and once free breathing (i.e. FTBH). Positional impact was evaluated using overlap index (OI) and Dice similarity coefficient (DSC). Dosimetrical impact was assessed by beam transposition from the baseline plan. Mean OI and DSC ranges were 0.01-0.98 and 0.01-0.92 for FTBH, and 0.73-1 and 0.69-1 for RBH. Dosimetric impact of RBH was negligible. FTBH significantly decreased minimal dose to CTV WBI, level II and the internal mammary nodes, with adequate mean doses. FTBH significantly increased heart, LAD, left lung and esophagus dose. OI and DSC for RBH and FTBH show reproducible large ROI positions. Small ROIs show poor overlap. FTBH maintained adequate target coverage but increased heart, LAD, ipsilateral lung and esophagus dose. RBH is a robust technique in pWB + RNI. (Clinicaltrials.gov: NCT05179161, registered 05/01/2022)., (© 2022. The Author(s).)

Introduction: Postmastectomy radiotherapy reduces the risk of locoregional recurrence in breast cancer patients. The first results on accelerated radiotherapy in five fractions after breast conserving surgery are promising. The data on postmastectomy radiotherapy in five or six fractions is limited. We now present the data on acute and one-year toxicity and health related quality of life (HRQoL) after postmastectomy radiotherapy in patients of sixty years or older., Methodology: 119 patients received five fractions of 5.7 Gy to the chest wall and five fractions of 5.4 Gy to the lymph nodes over ten to twelve days. Physician-assessed toxicity were scored using the Common Terminology Criteria for Adverse Events version 4.03 toxicity scoring system and the LENT-SOMA scale. Fatigue was measured by the Multidimensional Fatigue Inventory (MFI-206). HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire the breast cancer specific module and the BREAST-Q questionnaire., Results: Fatigue and edema were the most frequently observed physician-assessed toxicities. One year after radiotherapy only 12.9% experienced a clinically important deterioration in chest wall symptoms and in 22.9% of the patients were improved. Future perspective at one year after radiotherapy was improved in 40.0% of the patients. Patient-reported fatigue showed the greatest improvement., Conclusion: Accelerated radiotherapy should be considered to minimize the burden of breast cancer treatment, especially in older patients.

Purpose: Prone position for whole breast irradiation (WBI) results in lower rates of toxicity and reduced ipsilateral mean lung and heart doses. No randomized trials comparing toxicity and cosmesis at 5 years with prone and supine positioning are available., Methods and Materials: In this phase 2 open-label trial, 100 patients with large breast size requiring WBI were randomized between prone and supine positioning. Physician-assessed toxicity (retraction, fibrosis, edema, telangiectasia, pigmentation changes) was scored yearly for a total of 5 years, and photographs were taken at 5 years to assess cosmesis. The data were analyzed longitudinally and cross-sectionally., Results: Longitudinal analysis shows lower grade 2 late toxicity with prone positioning. The results for at least grade 1 physician-assessed toxicity at 5 years are similar between supine and prone position, respectively, for retraction (56% vs 54%), fibrosis outside the tumor bed (33% vs 24%), tumor bed fibrosis (49% vs 46%), edema (11% vs 8%), telangiectasia (8% vs 3%), and breast pain (6% vs 8%) using cross-sectional analysis. However, the risk of pigmentation changes in prone position (0% vs 19%) 5 years after radiation therapy was significantly lower. Cosmesis was good or excellent in 92% and 75% of patients who used prone and supine positioning, respectively. The 5-year overall survival is 96% in both groups., Conclusion: Prone positioning results in reduced rates of late toxicity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: A simultaneous integrated boost (SIB) leads to less acute toxicity. Less is known for late toxicity due to SIB. In this first and only randomized trial, two-years toxicity is analysed., Materials and Methods: Physician-assessed toxicity, using the LENT SOMA scale, and photographs, analysed with the BCCT.core software, was examined for 150 patients, randomized between SIB and sequential boost (SEB)., Results: Differences in physician-assessed two-years toxicity and photographic analysis between SIB and SEB are very small and not significant., Conclusion: There is no indication that a SIB leads to an excess in toxicity or worse cosmetic outcome at 2 years., Competing Interests: Conflict of interest This work was supported by the Cancer Plan Action 29 (project 015 and 008) by the Federal Public Service of Health, Food Chain Safety and Environment, Belgium and by grants of Stand up to Cancer (Flemish Cancer Society) and Foundation against Cancer (FAF-C/2016/854). Liv Veldeman holds a Clinical Mandate of Foundation against Cancer. None of the other auteurs have a conflict of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We report on a comparative dosimetrical study between deep inspiration breath hold (DIBH) and shallow breathing (SB) in prone crawl position for photon and proton radiotherapy of whole breast (WB) and locoregional lymph node regions, including the internal mammary chain (LN&#95;MI). We investigate the dosimetrical effects of DIBH in prone crawl position on organs-at-risk for both photon and proton plans. For each modality, we further estimate the effects of lung and heart doses on the mortality risks of different risk profiles of patients. Thirty-one patients with invasive carcinoma of the left breast and pathologically confirmed positive lymph node status were included in this study. DIBH significantly decreased dose to heart for photon and proton radiotherapy. DIBH also decreased lung doses for photons, while increased lung doses were observed using protons because the retracting heart is displaced by low-density lung tissue. For other organs-at-risk, DIBH resulted in significant dose reductions using photons while minor differences in dose deposition between DIBH and SB were observed using protons. In patients with high risks for cardiac and lung cancer mortality, average thirty-year mortality rates from radiotherapy-related cardiac injury and lung cancer were estimated at 3.12% (photon DIBH), 4.03% (photon SB), 1.80% (proton DIBH) and 1.66% (proton SB). The radiation-related mortality risk could not outweigh the ~ 8% disease-specific survival benefit of WB + LN&#95;MI radiotherapy in any of the assessed treatments.

Introduction: Acceleration of radiotherapy in 5 fractions for breast cancer can reduce the burden of treatment. We report on acute toxicity after whole-breast irradiation with a simultaneous integrated boost in 5 fractions over 10-12 days., Material and Methods: Acute toxicity and health-related quality of life (HRQoL) of 200 patients, randomized between a 15- or 5-fractions schedule, were collected, using the CTCAE toxicity scoring system, the Multidimensional Fatigue Inventory, EORTC QLQ-C30 and BR23 and the BREAST-Q questionnaire. The prescribed dose to the breast was either 15∗2.67 Gy (40.05 Gy) or 5∗5.7 Gy (28.5 Gy). 90% of patients received a SIB to a cumulative dose of 46.8 Gy (15∗3.12 Gy) or 31 Gy (5∗6.2 Gy)., Results: Physician-assessed toxicity was lower for the 5-fractions group. A significant difference was observed for breast pain (p = 0.002), fatigue (p < 0.0001), breast edema (p = 0.001) and dermatitis (p = 0.003). Patients treated in 5 fractions reported better mean HRQoL scores for breast symptoms (p = 0.001) and physical well-being (p = 0.001). A clinically important deterioration in HRQoL of 10 points or more was also less frequently observed in the latter group for physical functioning (p = 0.0005), social functioning (p = 0.0007), fatigue (p = 0.003), breast symptoms (p = 0.0002) and physical well-being (p = 0.002)., Conclusion: In this single institute study, acute toxicity of accelerated breast radiotherapy in 5 fractions over 10-12 days seems to compare favourably to hypofractionated breast radiotherapy in 15 fractions. Less breast edema, dermatitis, desquamation, breast pain and fatigue are seen. Social and physical functioning are also less disturbed and patients have a better future perspective., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Prone positioning for whole-breast irradiation (WBI) reduces dose to organs at risk, but reduces set-up speed, precision, and comfort. We aimed to improve these problems by placing patients in prone crawl position on a newly developed crawl couch (CrC). A group of 10 right-sided breast cancer patients requiring WBI were randomized in this cross-over trial, comparing the CrC to a standard prone breastboard (BB). Laterolateral (LL), craniocaudal (CC) and anterioposterior (AP) set-up errors were evaluated with cone beam CT. Comfort, preference and set-up time (SUT) were assessed. Forty left and right-sided breast cancer patients served as a validation group. For BB versus CrC, AP, LL and CC mean patient shifts were - 0.8 ± 2.8, 0.2 ± 11.7 and - 0.6 ± 4.4 versus - 0.2 ± 3.3, - 0.8 ± 2.5 and - 1.9 ± 5.7 mm. LL shift spread was reduced significantly. Nine out of 10 patients preferred the CrC. SUT did not differ significantly. The validation group had mean patient shifts of 1.7 ± 2.9 (AP), 0.2 ± 3.6 (LL) and - 0.2 ± 3.3 (CC) mm. Mean SUT in the validation group was 1 min longer (P < 0.05) than the comparative group. Median SUT was 3 min in all groups. The CrC improved precision and comfort compared to BB. Set-up errors compare favourably to other prone-WBI trials and rival supine positioning.

Although many authors stated that a user-centred design approach in medical device development has added values, the most common research approach within healthcare is evidence-based medicine, which tend to focus on functional data rather than patient wellbeing and comfort. End user comfort is well addressed in literature for commercial products such as seats and hand tools but no data was found for medical devices. A commercial patient support device for breast radiotherapy was analysed and a relation was found between discomfort and uncompensated internal body forces. Derived from CT-images, simplified patient free-body diagrams were analysed and pain and comfort evaluated. Subsequently, a new patient position was established and prototypes were developed. Patient comfort- and prototype optimization was done through iterative prototyping. With this approach, we were able to compensate all internal body forces and establish a force neutral patient free-body diagram. This resulted in comfortable patient positioning and favourable medical results., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: To investigate, in a prospective phase 1 to 2 trial, the safety and feasibility of delivering external beam radiation therapy in 5 fractions to the breast or thoracic wall, including boost and/or lymph nodes if needed, to women aged ≥65 years with breast cancer., Methods and Materials: Ninety-five patients aged ≥65 years, referred for adjuvant radiation therapy, were treated in 5 fractions over 12 days with a total dose of 28.5 Gy/5.7 Gy to the breast or thoracic wall and, if indicated, 27 Gy/5.4 Gy to the lymph node regions and 32.5 Gy/6.5 Gy to 34.5 Gy/6.9 Gy to the tumor bed. The primary endpoint was clinically relevant dermatitis (grade ≥2)., Results: Mean follow-up time was 5.6 months, and mean age was 73.6 years. Clinically relevant dermatitis was observed in 11.6% of patients and only occurred in breast irradiation with boost (17.5% grade 2-3 vs 0% in the no-boost group). Although doses were high, treatment delivery with intensity modulated radiation therapy was swift, except for complex treatments, including lymph nodes for which single-arc volumetric modulated arc therapy was needed to reduce beam-on time., Conclusion: Accelerated radiation therapy in 5 fractions was technically feasible and resulted in low acute toxicity. Clinically relevant erythema was only observed in patients receiving a boost, but still at an acceptable rate. Although the follow-up is still short, the results on acute toxicity after accelerated radiation therapy were encouraging. A 5-fraction schedule is well tolerated in the elderly and may lower the threshold for radiation therapy in this population., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To investigate crawl position with the arm at the treated side alongside the body and at the opposite side above the head for prone treatment in patients requiring breast and regional lymph node irradiation., Methods: Patient support devices for crawl position were built for CT simulation and treatment. An asymmetric fork design resulted from an iterative process of prototype construction and testing. The fork's large horn supports the hemi-thorax, shoulder, and elevated arm at the nontreated side and the head. The short, narrow horn supports the arm at the treated side. Between both horns, the treated breast and its regional lymph nodes are exposed. Endpoints were pain, comfort, set-up precision, beam access to the breast and lymph nodes, and plan dose metrics. Pain and comfort were tested by volunteers (n = 9); set-up precision, beam access, and plan dose metrics were tested by means of a patient study (n = 10). The AIO™ (Orfit, Wijnegem, Belgium) prone breastboard (AIO™) was used as a reference regarding comfort and set-up precision., Results: Pain at the sternum, the ipsilateral shoulder, upper arm, and neck was lower in crawl position than with bilateral arm elevation on AIO™. Comfort and set-up precision were better on the crawl prototype than on AIO™. In crawl position, beam directions in the coronal and near-sagittal planes have access to the breast or regional lymph nodes without traversing device components. Plan comparison between supine and crawl positions showed better dose homogeneity for the breast and lymph node targets and dose reductions to all organs at risk for crawl position., Conclusions: Radiation therapy for breast and regional lymph nodes in crawl position is feasible. Good comfort and set-up precision were demonstrated. Planning results support the hypothesis that breast and regional lymph nodes can be treated in crawl position with less dose to organs at risk and equal or better dose distribution in the target volumes than in supine position. The crawl technique is a candidate methodology for further investigation for patients requiring breast and regional lymph node irradiation., (© 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Background: Prone whole breast irradiation (WBI) leads to reduced heart and lung doses in breast cancer patients receiving adjuvant radiotherapy. In this feasibility trial, we investigated the prone position for whole breast + lymph node irradiation (WB + LNI)., Methods: A new support device was developed for optimal target coverage, on which patients are positioned in a position resembling a phase from the crawl swimming technique (prone crawl position). Five left sided breast cancer patients were included and simulated in supine and prone position. For each patient, a treatment plan was made in prone and supine position for WB + LNI to the whole axilla and the unoperated part of the axilla. Patients served as their own controls for comparing dosimetry of target volumes and organs at risk (OAR) in prone versus in supine position., Results: Target volume coverage differed only slightly between prone and supine position. Doses were significantly reduced (P < 0.05) in prone position for ipsilateral lung (Dmean, D2, V5, V10, V20, V30), contralateral lung (Dmean, D2), contralateral breast (Dmean, D2 and for total axillary WB + LNI also V5), thyroid (Dmean, D2, V5, V10, V20, V30), oesophagus (Dmean and for partial axillary WB + LNI also D2 and V5), skin (D2 and for partial axillary WB + LNI V105 and V107). There were no significant differences for heart and humeral head doses., Conclusions: Prone crawl position in WB + LNI allows for good breast and nodal target coverage with better sparing of ipsilateral lung, thyroid, contralateral breast, contralateral lung and oesophagus when compared to supine position. There is no difference in heart and humeral head doses., Trial Registration: No trial registration was performed because there were no therapeutic interventions.

Introduction: To report the impact on target volume delineation and dose to normal tissue using anatomic versus biological imaging ( 18 F-FDG-PET) for bone metastases., Methods: Patients with uncomplicated painful bone metastases were randomized (1:1:1) and blinded to receive either 8 Gy in a single fraction with conventionally planned radiotherapy (ConvRT-8 Gy) or 8 Gy in a single fraction with dose-painting-by-numbers (DPBN) dose range between 6 and 10 Gy) (DPBN-8 Gy) or 16 Gy in a single fraction with DPBN (dose range between 14 and 18 Gy) (DPBN-16 Gy). The primary endpoint was overall pain response at 1 month. Volumes of the gross tumour volume (GTV) - both biological (GTV PET ) and anatomical (GTV CT ) -, planning target volume (PTV), dose to the normal tissue and maximum standardized-uptake values (SUV MAX ) were analysed (secondary endpoint)., Results: Sixty-three percent of the GTV CT volume did not show 18 F-FDG-uptake. On average, 20% of the GTV PET volume was outside GTV CT . The volume of normal tissue receiving 4 Gy, 6 Gy and 8 Gy was at least 3×, 6× and 13× smaller in DPBN-8 Gy compared to ConvRT-8 Gy and DPBN-16 Gy (P < 0.05)., Conclusion: Positron emitting tomography-information potentially changes the target volume for bone metastases. DPBN between 6 and 10 Gy significantly decreases dose to the normal tissue compared to conventional radiotherapy., (© 2016 The Royal Australian and New Zealand College of Radiologists.)

Background and Purpose: The safety of a simultaneous integrated boost (SIB) in combination with prone hypofractionated whole-breast irradiation (WBI) was investigated., Materials and Methods: 167 patients were randomized between WBI with a sequential boost (SeB) or SIB. All patients were treated in prone position to 40.05Gy in 15 fractions to the whole breast. In the control arm, a SeB of 10Gy in 4 fractions (negative surgical margins) or 14.88Gy in 6 fractions (transsection) was prescribed. In the experimental arm a SIB of 46.8 or 49.95Gy (negative and positive surgical margins, respectively) was prescribed., Results: Patient age was the only significantly different parameter between treatment arms with patients in the SIB arm being slightly older. In both arms, 6/83 patients developed moist desquamation. Grade 2/3 dermatitis was significantly more frequent in the SeB arm (38/83vs 24/83 patients, p=0.037). In the SIB and SeB arm, respectively, 36 patients (43%) and 51 patients (61%) developed pruritus (p=0.015). The incidence of oedema was lower in the SIB arm (59vs 68 patients), but not statistically significant (p=0.071)., Conclusions: The primary endpoint, moist desquamation, was not significantly different between treatment arms., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: This study investigates the implementation of a new intensity modulated arc therapy (IMAT) class solution in comparison to a 6-static beam step-and-shoot intensity modulated radiotherapy (s-IMRT) for three-phase adaptive (18)F-FDG-PET-voxel-based dose-painting-by-numbers (DPBN) for head-and-neck cancer., Methods: We developed (18)F-FDG-PET-voxel intensity-based IMAT employing multiple arcs and compared it to clinically used s-IMRT DPBN. Three IMAT plans using (18)F-FDG-PET/CT acquired before treatment (phase I), after 8 fractions (phase II) and CT acquired after 18 fractions (phase III) were generated for each of 10 patients treated with 3 s-IMRT plans based on the same image sets. Based on deformable image registration (ABAS, version 0.41, Elekta CMS Software, Maryland Heights, MO), doses of the 3 plans were summed on the pretreatment CT using validated in-house developed software. Dosimetric indices in targets and organs-at-risk (OARs), biologic conformity of treatment plans set at ≤5 %, treatment quality and efficiency were compared between IMAT and s-IMRT for the whole group and for individual patients., Results: Doses to most organs-at-risk (OARs) were significantly better in IMAT plans, while target levels were similar for both types of plans. On average, IMAT ipsilateral and contralateral parotid mean doses were 14.0 % (p = 0.001) and 12.7 % (p < 0.001) lower, respectively. Pharyngeal constrictors D50% levels were similar or reduced with up to 54.9 % for IMAT compared to s-IMRT for individual patient cases. IMAT significantly improved biologic conformity by 2.1 % for treatment phases I and II. 3D phantom measurements reported an agreement of ≥95 % for 3 % and 3 mm criteria for both treatment modalities. IMAT delivery time was significantly shortened on average by 41.1 %., Conclusions: IMAT implementation significantly improved the biologic conformity as compared to s-IMRT in adaptive dose-escalated DPBN treatments. The better OAR sparing and faster delivery highly improved the treatment efficiency.

Purpose: To evaluate cone-beam computed tomography (CBCT) based setup accuracy and margins for prone and supine whole breast irradiation (WBI)., Methods: Setup accuracy was evaluated on 3559 CBCT scans of 242 patients treated with WBI and uncertainty margins were calculated using the van Herk formula. Uni- and multivariate analysis on individual margins was performed for age, body mass index (BMI) and cup size., Results: The population-based margin in vertical (VE), lateral (LA) and longitudinal (LO) directions was 10.4/9.4/9.4 mm for the 103 supine and 10.5/22.4/13.7 mm for the 139 prone treated patients, being significantly (p < 0.01) different for the LA and LO directions. Multivariate analysis identified a significant (p < 0.05) correlation between BMI and the LO margin in supine position and the VE/LA margin in prone position., Conclusion: In this series, setup accuracy is significantly worse in prone compared to supine position for the LA and LO directions. However, without proper image-guidance, uncertainty margins of about 1 cm are also necessary for supine WBI. For patients with a higher BMI, larger margins are required.

Deep inspiration breath hold in the prone position causes a caudal shift of the heart away from the nearly unmodified breast and internal mammary lymph node region, suggesting better heart protection for left-sided whole breast irradiation with or without regional nodal radiotherapy., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Antalgic radiotherapy for bone metastases might be improved by implementing biological information in the radiotherapy planning using (18)F-FDG-PET-CT based dose painting by numbers (DPBN)., Materials and Methods: Patients with uncomplicated painful bone metastases were randomized (1:1:1) and blinded to receive either 8Gy in a single fraction with conventionally planned radiotherapy (arm A) or 8Gy in a single fraction with DPBN (dose range between 610Gy and 10Gy) (arm B) or 16Gy in a single fraction with DPBN (dose range between 1410Gy and 18Gy) (arm C). The primary endpoint was overall pain response at 1month. The phase II trial was designed to select the experimental arm with sufficient promise of efficacy to continue to a phase III trial., Results: Forty-five patients were randomized. Eight (53%), 12 (80%) and 9 patients (60%) had an overall response to treatment in arm A, B and C, respectively. The estimated odds ratio of overall response for arm B vs. A is 3.5 (95% CI: 0.44-17.71, p=0.12). The estimated odds ratio of arm C vs. A is 1.31 (95% CI: 0.31-5.58, p=0.71)., Conclusion: A single fraction of 8Gy with DPBN will be further evaluated in a phase III-trial., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Investigating reproducibility and instability of deep inspiration breath hold (DIBH) in the prone position to reduce heart dose for left-sided whole breast irradiation., Methods: Thirty patients were included and underwent 2 prone DIBH CT-scans during simulation. Overlap indices were calculated for the ipsilateral breast, heart and lungs to evaluate the anatomical reproducibility of the DIBH maneuver. The breathing motion of 21 patients treated with prone DIBH were registered using magnetic probes. These breathing curves were investigated to gain data on intra-fraction reproducibility and instability of the different DIBH cycles during treatment., Results: Overlap index was 0.98 for the ipsilateral breast and 0.96 for heart and both lungs between the 2 prone DIBH-scans. The magnetic sensors reported population amplitudes of 2.8 ± 1.3 mm for shallow breathing and 11.7 ± 4.7 mm for DIBH, an intra-fraction standard deviation of 1.0 ± 0.4 mm for DIBH, an intra-breath hold instability of 1.0 ± 0.6 mm and a treatment time of 300 ± 69 s., Conclusion: Prone DIBH can be accurately clinically implemented with acceptable reproducibility and instability.

Background and Purpose: Cardiac disease has been related to heart dose after left-sided breast radiotherapy. This trial evaluates the heart sparing ability and feasibility of deep inspiration breath hold (DIBH) in the prone position for left-sided whole breast irradiation (WBI)., Materials and Methods: Twelve patients underwent CT-simulation in supine shallow breathing (SB), supine DIBH, prone SB and prone DIBH. A validation cohort of 38 patients received prone SB and prone DIBH CT-scans; the last 30 patients were accepted for prone DIBH treatment. WBI was planned with a prescription dose of 40.05 Gy., Results: DIBH was able to reduce (p<0.001) heart dose in both positions, with results for prone DIBH at least as favorable as for supine DIBH. Mean heart dose was lowered from 2.2 Gy for prone SB to 1.3 Gy for prone DIBH (p<0.001), while preserving the lung sparing ability of prone positioning. Moreover prone DIBH nearly consistently reduced mean heart dose to less then 2 Gy, regardless of breast volume. All patients were able to perform the simulation procedure, 28/30 patients were treated with prone DIBH., Conclusions: This trial demonstrates the ability and feasibility of prone DIBH to acquire optimal heart and lung sparing for left-sided WBI., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To report the dosimetric results and impact of volumetric arc therapy (VMAT) on temporary alopecia and hair-loss related quality of life (QOL) in whole brain radiotherapy (WBRT)., Methods: The potential of VMAT-WBRT to reduce the dose to the hair follicles was assessed. A human cadaver was treated with both VMAT-WBRT and conventional opposed field (OF) WBRT, while the subcutaneously absorbed dose was measured by radiochromic films and calculated by the planning system. The impact of these dose reductions on temporary alopecia was examined in a prospective phase II trial, with the mean score of hair loss at 1 month after VMAT-WBRT (EORTC-QOL BN20) as a primary endpoint and delivering a dose of 20 Gy in 5 fractions. An interim analysis was planned after including 10 patients to rule out futility, defined as a mean score of hair loss exceeding 56.7. A secondary endpoint was the global alopecia areata severity score measured with the "Severity of Alopecia Tool" (SALT) with a scale of 0 (no hair loss) to 100 (complete alopecia)., Results: For VMAT-WBRT, the cadaver measurements demonstrated a dose reduction to the hair follicle volume of 20.5% on average and of 41.8% on the frontal-vertex-occipital medial axis as compared to OF-WBRT. In the phase II trial, a total of 10 patients were included before the trial was halted due to futility. The EORTC BN20 hair loss score following WBRT was 95 (SD 12.6). The average median dose to the hair follicle volume was 12.6 Gy (SD 0.9), corresponding to a 37% dose reduction compared to the prescribed dose. This resulted in a mean SALT-score of 75., Conclusions: Compared to OF-WBRT, VMAT-WBRT substantially reduces hair follicle dose. These dose reductions could not be related to an improved QOL or SALT score.

Purpose: To develop contouring guidelines for the brachial plexus (BP) using anatomically validated cadaver datasets. Magnetic resonance imaging (MRI) and computed tomography (CT) were used to obtain detailed visualizations of the BP region, with the goal of achieving maximal inclusion of the actual BP in a small contoured volume while also accommodating for anatomic variations., Methods and Materials: CT and MRI were obtained for 8 cadavers positioned for intensity modulated radiation therapy. 3-dimensional reconstructions of soft tissue (from MRI) and bone (from CT) were combined to create 8 separate enhanced CT project files. Dissection of the corresponding cadavers anatomically validated the reconstructions created. Seven enhanced CT project files were then automatically fitted, separately in different regions, to obtain a single dataset of superimposed BP regions that incorporated anatomic variations. From this dataset, improved BP contouring guidelines were developed. These guidelines were then applied to the 7 original CT project files and also to 1 additional file, left out from the superimposing procedure. The percentage of BP inclusion was compared with the published guidelines., Results: The anatomic validation procedure showed a high level of conformity for the BP regions examined between the 3-dimensional reconstructions generated and the dissected counterparts. Accurate and detailed BP contouring guidelines were developed, which provided corresponding guidance for each level in a clinical dataset. An average margin of 4.7 mm around the anatomically validated BP contour is sufficient to accommodate for anatomic variations. Using the new guidelines, 100% inclusion of the BP was achieved, compared with a mean inclusion of 37.75% when published guidelines were applied., Conclusion: Improved guidelines for BP delineation were developed using combined MRI and CT imaging with validation by anatomic dissection., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Development and implementation of chronological and anti-chronological adaptive dose accumulation strategies in adaptive intensity-modulated radiation therapy (IMRT) for head-and-neck cancer. An algorithm based on Newton iterations was implemented to efficiently compute inverse deformation fields (DFs). Four verification steps were performed to ensure a valid dose propagation: intra-cell folding detection finds zero or negative Jacobian determinants in the input DF; inter-cell folding detection is implemented on the resolution of the output DF; a region growing algorithm detects undefined values in the output DF; DF domains can be composed and displayed on the CT data. In 2011, one patient with nonmetastatic head and neck cancer selected from a three phase adaptive DPBN study was used to illustrate the algorithms implemented for adaptive chronological and anti-chronological dose accumulation. The patient received three (18)F-FDG-PET/CTs prior to each treatment phase and one CT after finalizing treatment. Contour propagation and DF generation between two consecutive CTs was performed in Atlas-based autosegmentation (ABAS). Deformable image registration based dose accumulations were performed on CT1 and CT4. Dose propagation was done using combinations of DFs or their inversions. We have implemented a chronological and anti-chronological dose accumulation algorithm based on DF inversion. Algorithms were designed and implemented to detect cell folding.

Background and Purpose: Comparison of acute toxicity of whole-breast irradiation (WBI) in prone and supine positions., Materials and Methods: This non-blinded, randomized, prospective, mono-centric trial was undertaken between December 29, 2010, and December 12, 2012. One hundred patients with large breasts were randomized between supine multi beam (MB) and prone tangential field (TF) intensity modulated radiotherapy (IMRT). Dose-volume parameters were assessed for the breast, heart, left anterior descending coronary artery (LAD), ipsilateral lung and contralateral breast. The primary endpoint was acute moist skin desquamation. Secondary endpoints were dermatitis, edema, pruritus and pain., Results: Prone treatment resulted in: improved dose coverage (p<0.001); better homogeneity (p<0.001); less volumes of over-dosage (p=0.001); reduced acute skin desquamation (p<0.001); a 3-fold decrease of moist desquamation p=0.04 (chi-square), p=0.07 (Fisher's exact test)); lower incidence of dermatitis (p<0.001), edema (p=0.005), pruritus (p=0.06) and pain (p=0.06); 2- to 4-fold reduction of grades 2-3 toxicity; lower ipsilateral lung (p<0.001) and mean LAD (p=0.007) dose; lower, though statistically non-significant heart and maximum LAD., Conclusions: This study provides level I evidence for replacing the supine standard treatment by prone IMRT for whole-breast irradiation in patients with large breasts. A confirmatory trial in a multi-institutional setting is warranted., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)