The added value of a new high-performance ring-gantry CBCT imaging system for prostate cancer patients.

BACKGROUND AND PURPOSE: A novel Cone-Beam Computed Tomography (CBCT) named HyperSight provides superior CBCT image quality compared to conventional ring gantry CBCT imaging, and it is suitable for dose calculations for prostate cancer, but it comes with considerable additional costs. The aim of this study was to determine the added value of HyperSight CBCT imaging compared to conventional CBCT imaging in terms of organ visibility in the male pelvic region. MATERIALS AND METHODS: Twenty prostate cancer patients were included in this prospective clinical study. For each patient three CBCT pairs, consisting of HyperSight and conventional CBCT scans acquired on consecutive days, were included. CBCT scans were evaluated by four observers in terms of visibility of the prostate, bladder, rectum and seminal vesicles. Visibility was scored on a 1-to-5 scale and by annotating axial slices where the organs were hard to delineate. Lastly, observers indicated whether the CBCT scans were of sufficient quality for an online adaptive radiation therapy workflow. RESULTS: All four organs were better visible on HyperSight CBCT scans compared to conventional CBCT scans. The mean visibility scores increased from 3.1 to 4.5 on a 1--5 scale of and the mean number of annotated slices reduced from 4.5 to 1.1. 99% Of the HyperSight CBCT scans were considered suitable for an online adaptive workflow vs 25-83% for the conventional CBCT scans. CONCLUSION: HyperSight CBCT scans yielded a visibility of prostate, bladder, rectum and seminal vesicles comparable to planning CT scans and, ccan replace a repeat planning CT scan in case of anatomical changes requiring a new treatment plan.

Clinical practicality and patient performance for surface-guided automated VMAT gating for DIBH breast cancer radiotherapy.

BACKGROUND AND PURPOSE: To evaluate the performance of automated surface-guided gating for left-sided breast cancer with DIBH and VMAT. MATERIALS AND METHODS: Patients treated in the first year after introduction of DIBH with VMAT were retrospectively considered for analysis. With automated surface-guided gating the beam automatically switches on/off, if the surface region of interest moved in/out the gating tolerance (±3 mm, ±3°). Patients were coached to hold their breath as long as comfortably possible. Depending on the patient's preference, patients received audio instructions during treatment delivery. Real-time positional variations of the breast/chest wall surface with respect to the reference surface were collected, for all three orthogonal directions. The durations and number of DIBHs needed to complete dose delivery, and DIBH position variations were determined. To evaluate an optimal gating window threshold, smaller tolerances of ±2.5 mm, ±2.0 mm, and ±1.5 mm were simulated. RESULTS: 525 fractions from 33 patients showed that median DIBH duration was 51 s (range: 30-121 s), and median 4 DIBHs per fraction were needed to complete VMAT dose delivery. Median intra-DIBH stability and intrafractional DIBH reproducibility approximated 1.0 mm in each direction. No large differences were found between patients who preferred to perform the DIBH procedure with (n = 21) and without audio-coaching (n = 12). Simulations demonstrated that gating window tolerances could be reduced from ±3.0 mm to ±2.0 mm, without affecting beam-on status. CONCLUSION: Independent of the use of audio-coaching, this study demonstrates that automated surface-guided gating with DIBH and VMAT proved highly efficient. Patients' DIBH performance far exceeded our expectations compared to earlier experiences and literature. Furthermore, gating window tolerances could be reduced.

Nine years of plan of the day for cervical cancer: Plan library remains effective compared to fully online-adaptive techniques.

BACKGROUND AND PURPOSE: Since 2011, our center has been using a library-based Plan-of-the-Day (PotD) strategy for external beam radiotherapy of cervical cancer patients to reduce normal tissue dose while maintaining adequate target coverage. With the advent of fully online-adaptive techniques such as daily online-adaptive replanning, further dose reduction may be possible. However, it is unknown how this reduction relates to plan library approaches, and how the most recent PotD strategies relate to no adaptation. In this study we compare the performance of our current PotD strategy with non-adaptive and fully online-adaptive techniques in terms of target volume size and normal tissue sparing. MATERIALS AND METHODS: Treatment data of 376 patients treated with the PotD protocol between June 2011 and April 2020 were included. The size of the Planning Target Volumes (PTVs) was reconstructed for different strategies: full online adaptation, no adaptation, and the latest clinical version of the PotD protocol. Normal tissue sparing was estimated by the difference in margin volume to construct the PTV and the volume overlap of the PTV with bladder and rectum. RESULTS: The current version of our PotD approach reduced the PTV margin volume by a median of 250 cm3 compared to no adaptation. Bladder-PTV overlap decreased from a median of 142 to 71 cm3, and from 39 to 16 cm3 for rectum-PTV. Fully online-adaptive approaches could further decrease the PTV volume by 144 cm3 using a 5 mm margin for residual errors. In this scenario, bladder-PTV overlap was reduced to 35 cm3 and rectum-PTV overlap to 11 cm3. CONCLUSION: The current version of the PotD protocol is an effective technique to improve normal tissue sparing compared to no adaptation. Further sparing can be achieved using fully online-adaptive techniques, but at the cost of a more complex workflow and with a potentially limited impact. PotD-type protocols can therefore be considered as a suitable alternative to fully online-adaptive approaches.

Corrigendum to "Evaluation of image-guided and surface-guided radiotherapy for breast cancer patients treated in deep inspiration breath-hold: A single institution experience" [Tech. Innov. Patient Support Radiat. Oncol. 21 (2022) 51-57].

[This corrects the article DOI: 10.1016/j.tipsro.2022.02.001.].

Evaluation of image-guided and surface-guided radiotherapy for breast cancer patients treated in deep inspiration breath-hold: A single institution experience.

INTRODUCTION: Nowadays, deep inspiratory breath-hold is a common technique to reduce heart dose in left-sided breast radiotherapy. This study evaluates the evolution of the breath-hold technique in our institute, from portal imaging during dose delivery to continuous monitoring with surface-guided radiotherapy (SGRT). MATERIALS AND METHODS: Setup data and portal imaging results were analyzed for 98 patients treated before 2014, and SGRT data for 228 patients treated between 2018 and 2020. For the pre-SGRT group, systematic and random setup errors were calculated for different correction protocols. Residual errors and reproducibility of breath-holds were evaluated for both groups. The benefit of using SGRT for initial positioning was evaluated for another cohort of 47 patients. RESULTS: Online correction reduced the population mean error from 3.9 mm (no corrections) to 1.4 mm. Despite online setup correction, deviations greater than 3 mm were observed in about 10% and 20% of the treatment beams in ventral-dorsal and cranial-caudal directions, respectively. However, these percentages were much smaller than with offline protocols or no corrections. Mean absolute differences between breath-holds within a fraction were smaller in the SGRT-group (1.69 mm) than in the pre-SGRT-group (2.10 mm), and further improved with addition of visual feedback (1.30 mm). SGRT for positioning did not improve setup accuracy, but slightly reduced the time for imaging and setup correction, allowing completion within 3.5 min for 95% of fractions. CONCLUSION: For accurate radiotherapy breast treatments using deep inspiration breath-hold, daily imaging and correction is required. SGRT provides accurate information on patient positioning during treatment and improves patient compliance with visual feedback.

Single-institution clinical experience using robust intensity modulated proton therapy in chordoma and chondrosarcoma of the mobile spine and sacrum: Feasibility and need for plan adaptation.

BACKGROUND: Due to its specific physical characteristics, proton irradiation is especially suited for irradiation of chordomas and chondrosarcoma in the axial skeleton. Robust plan optimization renders the proton beam therapy more predictable upon individual setup errors. Reported experience with the planning and delivery of robustly optimized plans in chordoma and chondrosarcoma of the mobile spine and sacrum, is limited. In this study, we report on the clinical use of robustly optimized, intensity modulated proton beam therapy in these patients. METHODS: We retrospectively reviewed patient, treatment and acute toxicity data of all patients with chordoma and chondrosarcoma of the mobile spine and sacrum, treated between 1 April 2019 and 1 April 2020 at our institute. Anatomy changes during treatment were evaluated by weekly cone-beam CTs (CBCT), supplemented by scheduled control-CTs or ad-hoc control-CTs. Acute toxicity was scored weekly during treatment and at 3 months after therapy according to CTCAE 4.0. RESULTS: 17 chordoma and 3 chondrosarcoma patients were included. Coverage of the high dose clinical target volume was 99.8% (range 56.1-100%) in the nominal and 80.9% (range 14.3-99.6%) in the voxel-wise minimum dose distribution. Treatment plan adaptation was needed in 5 out of 22 (22.7%) plans. Reasons for plan adaptation were either reduced tumor coverage or increased dose to the OAR. CONCLUSIONS: Robustly optimized intensity modulated proton beam therapy for chordoma and chondrosarcoma of the mobile spine is feasible. Plan adaptations due to anatomical changes were required in approximately 23 percent of treatment courses.

Identification of Risk of Cardiovascular Disease by Automatic Quantification of Coronary Artery Calcifications on Radiotherapy Planning CT Scans in Patients With Breast Cancer.

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 15 915 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 15 915 participants included in this study, the mean (SD) age at CT scan was 59.0 (11.2; range, 22-95) years, and 15 879 (99.8%) were women. Seventy percent (n = 11 179) 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.

On the Importance of Individualized, Non-Coplanar Beam Configurations in Mediastinal Lymphoma Radiotherapy, Optimized With Automated Planning.

BACKGROUND AND PURPOSE: Literature is non-conclusive regarding selection of beam configurations in radiotherapy for mediastinal lymphoma (ML) radiotherapy, and published studies are based on manual planning with its inherent limitations. In this study, coplanar and non-coplanar beam configurations were systematically compared, using a large number of automatically generated plans. MATERIAL AND METHODS: An autoplanning workflow, including beam configuration optimization, was configured for young female ML patients. For each of 25 patients, 24 plans with different beam configurations were generated with autoplanning: 11 coplanar CP_x plans and 11 non-coplanar NCP_x plans with x = 5 to 15 IMRT beams with computer-optimized, patient-specific configurations, and the coplanar VMAT and non-coplanar Butterfly VMAT (B-VMAT) beam angle class solutions (600 plans in total). RESULTS: Autoplans compared favorably with manually generated, clinically delivered plans, ensuring that beam configuration comparisons were performed with high quality plans. There was no beam configuration approach that was best for all patients and all plan parameters. Overall there was a clear tendency towards higher plan quality with non-coplanar configurations (NCP_x≥12 and B-VMAT). NCP_x≥12 produced highly conformal plans with on average reduced high doses in lungs and patient and also a reduced heart Dmean, while B-VMAT resulted in reduced low-dose spread in lungs and left breast. CONCLUSIONS: Non-coplanar beam configurations were favorable for young female mediastinal lymphoma patients, with patient-specific and plan-parameter-dependent dosimetric advantages of NCP_x≥12 and B-VMAT. Individualization of beam configuration approach, considering also the faster delivery of B-VMAT vs. NCP_x≥12, can importantly improve the treatments.

Model based patient pre-selection for intensity-modulated proton therapy (IMPT) using automated treatment planning and machine learning.

BACKGROUND AND PURPOSE: Patient selection for intensity modulated proton therapy (IMPT), using comparative photon therapy planning, is workload-intensive and time-consuming. Pre-selection aims at avoidance of manual IMPT planning for patients that are in the end ineligible. We investigated the use of machine learning together with automated IMPT treatment planning for pre-selection of head and neck cancer patients, and validated the methodology for the Dutch model based selection (MBS) approach. MATERIALS & METHODS: For forty-five head and neck patients with a previous MBS, an IMPT plan was generated with non-clinical, fully-automated planning. Dosimetric differences of these plans with the corresponding previously generated photon plans, and the outcomes of the former MBS, were used to train a Gaussian naïve Bayes classifier for MBS outcome prediction. During training, strong emphasis was placed on avoiding misclassification of IMPT eligible patients (i.e. false negatives). RESULTS: Pre-selection with the classifier resulted in 0 false negatives, 12 (27%) true negatives, 27 (60%) true positives, and only 6 (13%) false positive predictions. Using this pre-selection, the number of formal selection procedures with involved manual IMPT planning that resulted in a negative outcome could be reduced by 67%. CONCLUSION: With pre-selection, using machine learning and automated treatment planning, the percentage of patients with unnecessary manual IMPT planning for MBS could be drastically reduced, thereby saving costs, labor and time. With the developed approach, larger patient populations can be screened, and likely bias in pre-selection of patients can be mitigated by assisting the physician during patient pre-selection.

Bragatston study protocol: a multicentre cohort study on automated quantification of cardiovascular calcifications on radiotherapy planning CT scans for cardiovascular risk prediction in patients with breast cancer.

INTRODUCTION: Cardiovascular disease (CVD) is an important cause of death in breast cancer survivors. Some breast cancer treatments including anthracyclines, trastuzumab and radiotherapy can increase the risk of CVD, especially for patients with pre-existing CVD risk factors. Early identification of patients at increased CVD risk may allow switching to less cardiotoxic treatments, active surveillance or treatment of CVD risk factors. One of the strongest independent CVD risk factors is the presence and extent of coronary artery calcifications (CAC). In clinical practice, CAC are generally quantified on ECG-triggered cardiac CT scans. Patients with breast cancer treated with radiotherapy routinely undergo radiotherapy planning CT scans of the chest, and those scans could provide the opportunity to routinely assess CAC before a potentially cardiotoxic treatment. The Bragatston study aims to investigate the association between calcifications in the coronary arteries, aorta and heart valves (hereinafter called 'cardiovascular calcifications') measured automatically on planning CT scans of patients with breast cancer and CVD risk. METHODS AND ANALYSIS: In a first step, we will optimise and validate a deep learning algorithm for automated quantification of cardiovascular calcifications on planning CT scans of patients with breast cancer. Then, in a multicentre cohort study (University Medical Center Utrecht, Utrecht, Erasmus MC Cancer Institute, Rotterdam and Radboudumc, Nijmegen, The Netherlands), the association between cardiovascular calcifications measured on planning CT scans of patients with breast cancer (n≈16 000) and incident (non-)fatal CVD events will be evaluated. To assess the added predictive value of these calcifications over traditional CVD risk factors and treatment characteristics, a case-cohort analysis will be performed among all cohort members diagnosed with a CVD event during follow-up (n≈200) and a random sample of the baseline cohort (n≈600). ETHICS AND DISSEMINATION: The Institutional Review Boards of the participating hospitals decided that the Medical Research Involving Human Subjects Act does not apply. Findings will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: NCT03206333.

Fully automated, multi-criterial planning for Volumetric Modulated Arc Therapy - An international multi-center validation for prostate cancer.

BACKGROUND AND PURPOSE: Reported plan quality improvements with autoplanning of radiotherapy of the prostate and seminal vesicles are poor. A system for automated multi-criterial planning has been validated for this treatment in a large international multi-center study. The system is configured with training plans using a mechanism that strives for quality improvements relative to those plans. MATERIAL AND METHODS: Each of the four participating centers included thirty manually generated clinical Volumetric Modulated Arc Therapy prostate plans (manVMAT). Ten plans were used for autoplanning training. The other twenty were compared with an automatically generated plan (autoVMAT). Plan evaluations considered dosimetric plan parameters and blinded side-by-side plan comparisons by clinicians. RESULTS: With equivalent Planning Target Volume (PTV) V95%, D2%, D98%, and dose homogeneity autoVMAT was overall superior for rectum with median differences of 3.4 Gy (p < 0.001) in Dmean, 4.0% (p < 0.001) in V60Gy, and 1.5% (p = 0.001) in V75Gy, and for bladder Dmean (0.9 Gy, p < 0.001). Also the clinicians' plan comparisons pointed at an overall preference for autoVMAT. Advantages of autoVMAT were highly treatment center- and patient-specific with overall ranges for differences in rectum Dmean and V60Gy of [-4,12] Gy and [-2,15]%, respectively. CONCLUSION: Observed advantages of autoplanning were clinically relevant and larger than reported in the literature. The latter is likely related to the multi-criterial nature of the applied autoplanning algorithm, with for each center a dedicated configuration that aims at plan improvements relative to its (clinical) training plans. Large variations among patients in differences between manVMAT and autoVMAT point at inconsistencies in manual planning.

Automated volumetric modulated arc therapy planning for whole pelvic prostate radiotherapy.

BACKGROUND: For several tumor entities, automated treatment planning has improved plan quality and planning efficiency, and may enable adaptive treatment approaches. Whole-pelvic prostate radiotherapy (WPRT) involves large concave target volumes, which present a challenge for volumetric arc therapy (VMAT) optimization. This study evaluates automated VMAT planning for WPRT-VMAT and compares the results with manual expert planning. METHODS: A system for fully automated multi-criterial plan generation was configured for each step of sequential-boost WPRT-VMAT, with final "autoVMAT" plans being automatically calculated by the Monaco treatment planning system (TPS; Elekta AB, Stockholm, Sweden). Configuration was based on manually generated VMAT plans (manualVMAT) of 5 test patients, the planning protocol, and discussions with the treating physician on wishes for plan improvements. AutoVMAT plans were then generated for another 30 evaluation patients and compared to manualVMAT plans. For all 35 patients, manualVMAT plans were optimized by expert planners using the Monaco TPS. RESULTS: AutoVMAT plans exhibited strongly improved organ sparing and higher conformity compared to manualVMAT. On average, mean doses (Dmean) of bladder and rectum were reduced by 10.7 and 4.5 Gy, respectively, by autoVMAT. Prostate target coverage (V95%) was slightly higher (+0.6%) with manualVMAT. In a blinded scoring session, the radiation oncologist preferred autoVMAT plans to manualVMAT plans for 27/30 patients. All treatment plans were considered clinically acceptable. The workload per patient was reduced by > 70 min. CONCLUSION: Automated VMAT planning for complex WPRT dose distributions is feasible and creates treatment plans that are generally dosimetrically superior to manually optimized plans.

Individualized Selection of Beam Angles and Treatment Isocenter in Tangential Breast Intensity Modulated Radiation Therapy.

PURPOSE AND OBJECTIVE: Propose a novel method for individualized selection of beam angles and treatment isocenter in tangential breast intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS: For each patient, beam and isocenter selection starts with the fully automatic generation of a large database of IMRT plans (up to 847 in this study); each of these plans belongs to a unique combination of isocenter position, lateral beam angle, and medial beam angle. The imposed hard planning constraint on patient maximum dose may result in plans with unacceptable target dose delivery. Such plans are excluded from further analyses. Owing to differences in beam setup, database plans differ in mean doses to organs at risk (OARs). These mean doses are used to construct 2-dimensional graphs, showing relationships between: (1) contralateral breast dose and ipsilateral lung dose; and (2) contralateral breast dose and heart dose (analyzed only for left-sided). The graphs can be used for selection of the isocenter and beam angles with the optimal, patient-specific tradeoffs between the mean OAR doses. For 30 previously treated patients (15 left-sided and 15 right-sided tumors), graphs were generated considering only the clinically applied isocenter with 121 tangential beam angle pairs. For 20 of the 30 patients, 6 alternative isocenters were also investigated. RESULTS: Computation time for automatic generation of 121 IMRT plans took on average 30 minutes. The generated graphs demonstrated large variations in tradeoffs between conflicting OAR objectives, depending on beam angles and patient anatomy. For patients with isocenter optimization, 847 IMRT plans were considered. Adding isocenter position optimization next to beam angle optimization had a small impact on the final plan quality. CONCLUSION: A method is proposed for individualized selection of beam angles in tangential breast IMRT. This may be especially important for patients with cardiac risk factors or an enhanced risk for the development of contralateral breast cancer.

Practical use of the extended no action level (eNAL) correction protocol for breast cancer patients with implanted surgical clips.

PURPOSE: To describe the practical use of the extended No Action Level (eNAL) setup correction protocol for breast cancer patients with surgical clips and evaluate its impact on the setup accuracy of both tumor bed and whole breast during simultaneously integrated boost treatments. METHODS AND MATERIALS: For 80 patients, two orthogonal planar kilovoltage images and one megavoltage image (for the mediolateral beam) were acquired per fraction throughout the radiotherapy course. For setup correction, the eNAL protocol was applied, based on registration of surgical clips in the lumpectomy cavity. Differences with respect to application of a No Action Level (NAL) protocol or no protocol were quantified for tumor bed and whole breast. The correlation between clip migration during the fractionated treatment and either the method of surgery or the time elapsed from last surgery was investigated. RESULTS: The distance of the clips to their center of mass (COM), averaged over all clips and patients, was reduced by 0.9 ± 1.2 mm (mean ± 1 SD). Clip migration was similar between the group of patients starting treatment within 100 days after surgery (median, 53 days) and the group starting afterward (median, 163 days) (p = 0.20). Clip migration after conventional breast surgery (closing the breast superficially) or after lumpectomy with partial breast reconstructive techniques (sutured cavity). was not significantly different either (p = 0.22). Application of eNAL on clips resulted in residual systematic errors for the clips' COM of less than 1 mm in each direction, whereas the setup of the breast was within about 2 mm of accuracy. CONCLUSIONS: Surgical clips can be safely used for high-accuracy position verification and correction. Given compensation for time trends in the clips' COM throughout the treatment course, eNAL resulted in better setup accuracies for both tumor bed and whole breast than NAL.

Surgical clips for position verification and correction of non-rigid breast tissue in simultaneously integrated boost (SIB) treatments.

BACKGROUND AND PURPOSE: The aim of this study is to investigate whether surgical clips in the lumpectomy cavity are representative for position verification of both the tumour bed and the whole breast in simultaneously integrated boost (SIB) treatments. MATERIALS AND METHODS: For a group of 30 patients treated with a SIB technique, kV and MV planar images were acquired throughout the course of the fractionated treatment. The 3D set-up error for the tumour bed was derived by matching the surgical clips (3-8 per patient) in two almost orthogonal planar kV images. By projecting the 3D set-up error derived from the planar kV images to the (u, v)-plane of the tangential beams, the correlation with the 2D set-up error for the whole breast, derived from the MV EPID images, was determined. The stability of relative clip positions during the fractionated treatment was investigated. In addition, for a subgroup of 15 patients, the impact of breathing was determined from fluoroscopic movies acquired at the linac. RESULTS: The clip configurations were stable over the course of radiotherapy, showing an inter-fraction variation (1 SD) of 0.5mm on average. Between the start and the end of the treatment, the mean distance between the clips and their center of mass was reduced by 0.9 mm. A decrease larger than 2mm was observed in eight patients (17 clips). The top-top excursion of the clips due to breathing was generally less than 2.5mm in all directions. The population averages of the difference (+/-1 SD) between kV and MV matches in the (u, v)-plane were 0.2+/-1.8mm and 0.9+/-1.5mm, respectively. In 30% of the patients, time trends larger than 3mm were present over the course of the treatment in either or in both kV and MV match results. Application of the NAL protocol based on the clips reduced the population mean systematic error to less than 2mm in all directions, both for the tumour bed and the whole breast. Due to the observed time trends, these systematic errors can be further reduced to about 1mm by using an eNAL protocol instead. CONCLUSIONS: The relative positions of implanted surgical clips in the lumpectomy cavity after breast-conserving surgery remain stable during the course of radiotherapy treatment. Application of a NAL or eNAL set-up correction protocol based on surgical clips allows for adequate treatment of both the tumour bed and the whole breast with tight CTV-PTV margins.

Chemical modification of colloidal masks for nanolithography.

A method is presented to tune the holes in colloidal masks used for nanolithography. Using a simple wet-chemical method, a thin layer of silica is grown on masks of silica particles. The size of the holes is controlled by the amount of tetraethoxysilane (TEOS) added. More accurate tuning of the hole size is possible in the presence of a calibrated seed dispersion of silica colloids. We demonstrate modified masks that were used to create arrays of metal nanoparticles with a size ranging from 400 nm, for unmodified masks, down to tens of nanometers. The method is easy-to-use, fast, and inexpensive.

Combined optical tweezers/ion beam technique to tune colloidal masks for nanolithography.

A method is presented to control the in-plane ordering, size, and interparticle distance of nanoparticles fabricated by evaporation through a mask of colloidal particles. The use of optical tweezers combined with critical point drying gives single-particle position control over the colloidal particles in the mask. This extends the geometry of the colloidal masks from (self-organized) hexagonal to any desired symmetry and spacing. Control over the mask's hole size is achieved by MeV ion irradiation, which causes the colloids to expand in the in-plane direction, thus shrinking the size of the holes. After modification of the mask, evaporation at different angles with respect to the mask gives additional control over structure and interparticle distance, allowing nanoparticles of different materials to be deposited next to each other. We demonstrate large arrays of metal nanoparticles with dimensions in the 15-30 nm range, with control over the interparticle distance and in-plane ordering.