Quantifying intrafractional gastric motion using auto-segmentation on MRI: Deformation and respiratory-induced displacement compared.

BACKGROUND AND PURPOSE: For accurate pre-operative gastric radiotherapy, intrafractional changes must be taken into account. The aim of this study is to quantify local gastric deformations and compare these deformations with respiratory-induced displacement. MATERIALS AND METHODS: Coronal 2D MRI scans (15-16 min; 120 repetitions of 25-27 interleaved slices) were obtained for 18 healthy volunteers. A deep-learning network was used to auto-segment the stomach. To separate out respiratory-induced displacements, auto-segmentations were rigidly shifted in superior-inferior (SI) direction to align the centre of mass (CoM) within every slice. From these shifted auto-segmentations, 3D iso-probability surfaces (isosurfaces) were established: a reference surface for POcc  = 0.50 and 50 other isosurfaces (from POcc  = 0.01 to 0.99), with POcc indicating the probability of occupation by the stomach. For each point on the reference surface, distances to all isosurfaces were determined and a cumulative Gaussian was fitted to this probability-distance dataset to obtain a standard deviation (SDdeform ) expressing local deformation. For each volunteer, we determined median and 98th percentile of SDdeform over the reference surface and compared these with the respiratory-induced displacement SDresp , that is, the SD of all CoM shifts (paired Wilcoxon signed-rank, α = 0.05). RESULTS: Larger deformations were mostly seen in the antrum and pyloric region. Median SDdeform (range, 2.0-2.9 mm) was smaller than SDresp (2.7-8.8 mm) for each volunteer (p < 0.00001); 98th percentile of SDdeform (3.2-7.3 mm) did not significantly differ from SDresp (p = 0.13). CONCLUSION: Locally, gastric deformations can be large. Overall, however, these deformations are limited compared to respiratory-induced displacement. Therefore, unless respiratory motion is considerably reduced, the need to separately include these deformation uncertainties in the treatment margins may be limited.

Effect of gastrointestinal gas on the temperature distribution in pancreatic cancer hyperthermia treatment planning.

PURPOSE: In pancreatic cancer treatment, hyperthermia can be added to increase efficacy of chemo- and/or radiotherapy. Gas in stomach, intestines and colon is often in close proximity to the target volume. We investigated the impact of variations in gastrointestinal gas (GG) on temperature distributions during simulated hyperthermia treatment (HT). METHODS: We used sets of one CT and eight cone-beam CT (CBCT) scans obtained prior to/during fractionated image-guided radiotherapy in four pancreatic cancer patients. In Plan2Heat, we simulated locoregional heating by an ALBA-4D phased array radiofrequency system and calculated temperature distributions for (i) the segmented CT (sCT), (ii) sCT with GG replaced by muscle (sCT0), (iii) sCT0 with eight different GG distributions as visible on CBCT inserted (sCTCBCT). We calculated cumulative temperature-volume histograms for the clinical target volume (CTV) for all ten temperature distributions for each patient and investigated the relationship between GG volume and change in ΔT50 (temperature increase at 50% of CTV volume). We determined location and volume of normal tissue receiving a high thermal dose. RESULTS: GG volume on CBCT varied greatly (9-991 cm3). ΔT50 increased for increasing GG volume; maximum ΔT50 difference per patient was 0.4-0.6 °C. The risk for GG-associated treatment-limiting hot spots appeared low. Normal tissue high-temperature regions mostly occurred anteriorly; their volume and maximum temperature showed moderate positive correlations with GG volume, while fat-muscle interfaces were associated with higher risks for hot spots. CONCLUSIONS: Considerable changes in volume and position of gastrointestinal gas can occur and are associated with clinically relevant tumor temperature differences.

The clinical benefit of hyperthermia in pancreatic cancer: a systematic review.

OBJECTIVE: In pancreatic cancer, which is therapy resistant due to its hypoxic microenvironment, hyperthermia may enhance the effect of radio(chemo)therapy. The aim of this systematic review is to investigate the validity of the hypothesis that hyperthermia added to radiotherapy and/or chemotherapy improves treatment outcome for pancreatic cancer patients. METHODS AND MATERIALS: We searched MEDLINE and Embase, supplemented by handsearching, for clinical studies involving hyperthermia in pancreatic cancer patients. The quality of studies was evaluated using the Oxford Centre for Evidence-Based Medicine levels of evidence. Primary outcome was treatment efficacy; we calculated overall response rate and the weighted estimate of the population median overall survival (mp) and compared these between hyperthermia and control cohorts. RESULTS: Overall, 14 studies were included, with 395 patients with locally advanced and/or metastatic pancreatic cancer of whom 248 received hyperthermia. Patients were treated with regional (n = 189), intraoperative (n = 39) or whole-body hyperthermia (n = 20), combined with chemotherapy, radiotherapy or both. Quality of the studies was low, with level of evidence 3 (five studies) and 4. The six studies including a control group showed a longer mp in the hyperthermia groups than in the control groups (11.7 vs. 5.6 months). Overall response rate, reported in three studies with a control group, was also better for the hyperthermia groups (43.9% vs. 35.3%). CONCLUSIONS: Hyperthermia, when added to chemotherapy and/or radiotherapy, may positively affect treatment outcome for patients with pancreatic cancer. However, the quality of the reviewed studies was limited and future randomised controlled trials are needed to establish efficacy.

Quality assurance of the PREOPANC trial (2012-003181-40) for preoperative radiochemotherapy in pancreatic cancer : The dummy run.

BACKGROUND: The Dutch Pancreatic Cancer Group initiated the national, multicentre, controlled PREOPANC trial, randomising between preoperative radiochemotherapy and direct explorative laparotomy for patients with (borderline) resectable pancreatic cancer. The aim of this dummy run is to evaluate compliance with the radiotherapy protocol of this trial, and the quality of delineation and radiation plans. METHODS: Eleven radiation oncology departments open for accrual of patients in the PREOPANC trial were provided with all necessary information of a selected 'dummy' patient. Each institute was asked to delineate the target volumes, including gross tumour volume, internal gross tumour volume (iGTV), internal clinical target volume, and planning target volume. The institutions were also asked to provide a radiation treatment plan in accordance with the PREOPANC trial protocol. RESULTS: The range of the iGTV was 19.3-77.2 cm3 with a mean iGTV of 41.5 cm3 (standard deviation 14.8 cm3). Nine institutions made a treatment plan using an arc technique for treatment delivery, one an intensity modulated technique and one a 3-field conformal technique. All institutions reached the prescribed target coverage, without exceeding the organs at risk constraints. The institution with the 3­field conformal technique was advised to use a more sophisticated technique (e. g. volumetric modulated arc therapy) to reduce the dose to the spinal cord. CONCLUSION: All institutions showed acceptable deviations from the PREOPANC trial protocol and achieved an acceptable quality of delineation and radiation technique. All institutions were allowed to continue participation in the PREOPANC trial.

Probabilistic treatment planning for pancreatic cancer treatment: prospective incorporation of respiratory motion shows only limited dosimetric benefit.

BACKGROUND: We introduced a probabilistic treatment planning approach that prospectively incorporates respiratory-induced motion in the treatment plan optimization. The aim of this study was to determine the potential dosimetric benefit by comparing this approach to the use of an internal target volume (ITV). MATERIAL AND METHOD: We retrospectively compared the probabilistic respiratory motion-incorporated (RMI) approach to the ITV approach for 18 pancreatic cancer patients, for seven simulated respiratory amplitudes from 5 to 50 mm in the superior-inferior (SI) direction. For each plan, we assessed the target coverage (required: D98%≥95% of 50 Gy prescribed dose). For the RMI plans, we investigated whether target coverage was robust against daily variations in respiratory amplitude. We determined the distance between the clinical target volume and the 30 Gy isodose line (i.e. dose gradient steepness) in the SI direction. To investigate the clinical benefit of the RMI approach, we created for each patient an ITV and RMI treatment plan for the three-dimensional (3D) respiratory amplitudes observed on their pretreatment 4D computed tomography (4DCT). We determined Dmean, V30Gy, V40Gy and V50Gy for the duodenum. RESULTS: All treatment plans yielded good target coverage. The RMI plans were robust against respiratory amplitude variations up to 10 mm, as D98% remained ≥95%. We observed steeper dose gradients compared to the ITV approach, with a mean decrease from 25.9 to 19.2 mm for a motion amplitude of 50 mm. For the 4DCT motion amplitudes, the RMI approach resulted in a mean decrease of 0.43 Gy, 1.1 cm3, 1.4 cm3 and 0.9 cm3 for the Dmean, V30Gy, V40Gy and V50Gy of the duodenum, respectively. CONCLUSION: The probabilistic treatment planning approach yielded significantly steeper dose gradients and therefore significantly lower dose to surrounding healthy tissues than the ITV approach. However, the observed dosimetric gain for clinically observed respiratory motion amplitudes for this patient group was limited.

Addition of MRI for CT-based pancreatic tumor delineation: a feasibility study.

PURPOSE: To assess the effect of additional magnetic resonance imaging (MRI) alongside the planning computed tomography (CT) scan on target volume delineation in pancreatic cancer patients. MATERIAL AND METHODS: Eight observers (radiation oncologists) from six institutions delineated the gross tumor volume (GTV) on 3DCT, and internal GTV (iGTV) on 4DCT of four pancreatic cancer patients, while MRI was available in a second window (CT + MRI). Variations in volume, generalized conformity index (CIgen), and overall observer variation, expressed as standard deviation (SD) of the distances between delineated surfaces, were analyzed. CIgen is a measure of overlap of the delineated iGTVs (1 = full overlap, 0 = no overlap). Results were compared with those from an earlier study that assessed the interobserver variation by the same observers on the same patients on CT without MRI (CT-only). RESULTS: The maximum ratios between delineated volumes within a patient were 6.1 and 22.4 for the GTV (3DCT) and iGTV (4DCT), respectively. The average (root-mean-square) overall observer variations were SD = 0.41 cm (GTV) and SD = 0.73 cm (iGTV). The mean CIgen was 0.36 for GTV and 0.37 for iGTV. When compared to the iGTV delineated on CT-only, the mean volumes of the iGTV on CT + MRI were significantly smaller (32%, Wilcoxon signed-rank, p < .0005). The median volumes of the iGTV on CT + MRI were included for 97% and 92% in the median volumes of the iGTV on CT. Furthermore, CT + MRI showed smaller overall observer variations (root-mean-square SD = 0.59 cm) in six out of eight delineated structures compared to CT-only (root-mean-square SD = 0.72 cm). However, large local observer variations remained close to biliary stents and pathological lymph nodes, indicating issues with instructions and instruction compliance. CONCLUSIONS: The availability of MRI images during target delineation of pancreatic cancer on 3DCT and 4DCT resulted in smaller target volumes and reduced the interobserver variation in six out of eight delineated structures.

Dosimetric effects of anatomical changes during fractionated photon radiation therapy in pancreatic cancer patients.

Pancreatic tumors show large interfractional position variation. In addition, changes in gastrointestinal gas volumes and body contour take place over the course of radiation therapy. We aimed to quantify the effect of these anatomical changes on target dose coverage, for the clinically used fiducial marker-based patient position verification and, for comparison, also for simulated bony anatomy-based position verification. Nine consecutive patients were included in this retrospective study. To enable fraction dose calculations on cone-beam CT (CBCT), the planning CT was deformably registered to each CBCT (13-15 per patient); gas volumes visible on CBCT were copied to the deformed CT. Fraction doses were calculated for the clinically used 10 MV VMAT treatment plan (with for the planning target volume (PTV): D98% = 95%), according to fiducial marker-based and bony anatomy-based image registrations. Dose distributions were rigidly summed to yield the accumulated dose. To evaluate target dose coverage, we defined an iCTV+5 mm volume, i.e., the internal clinical target volume (iCTV) expanded with a 5 mm margin to account for remaining uncertainties including delineation uncertainties. We analyzed D98% , Dmean , and D2% for iCTV+5 mm and PTV (i.e., iCTV plus 10 mm margin). We found that for fiducial marker-based registration, differences between fraction doses and planned dose were minimal. For bony anatomy-based registration, fraction doses differed considerably, resulting in large differences between planned and accumulated dose for some patients, up to a decrease in D98% of the iCTV+5 mm from 95.9% to 85.8%. Our study shows that fractionated photon irradiation of pancreatic tumors is robust against variations in body contour and gastrointestinal gas, with dose coverage only mildly affected. However, as a result of interfractional tumor position variations, target dose coverage can severely decline when using bony anatomy for patient position verification. Therefore, the use of intratumoral fiducial marker-based daily position verification is essential in pancreatic cancer patients.

Considerable pancreatic tumor motion during breath-holding.

BACKGROUND: Breath-holding (BH) is often used to reduce abdominal organ motion during radiotherapy. However, for inhale BH, abdominal tumor motion during BH has not yet been investigated. The aim of this study was to quantify tumor motion during inhale BH and tumor position variations between consecutive inhale BHs in pancreatic cancer patients. MATERIAL AND METHODS: Twelve patients with intratumoral fiducials were included and asked to perform three consecutive 30-second inhale BHs on each of three measurement days. During BH, lateral fluoroscopic movies were obtained and a two-dimensional (2D) image correlation algorithm was used to track the fiducials and the diaphragm, yielding the tumor and diaphragm motion during each BH. The tumor position variation between consecutive BHs was obtained from the difference in initial tumor position between consecutive BHs on a single measurement day. RESULTS: We observed tumor motion during BH with a mean absolute maximum displacement over all BHs of 4.2 mm (range 1.0-11.0 mm) in inferior-superior (IS) direction and 2.7 mm (range 0.5-8.0 mm) in anterior-posterior (AP) direction. We found only a moderate correlation between tumor and diaphragm motion in the IS direction (Pearson's correlation coefficient |r|>0.6 in 45 of 76 BHs). The mean tumor position variation between consecutive BHs was 0.2 [standard deviation (SD) 1.7] mm in the inferior direction and 0.5 (SD 0.8) mm in the anterior direction. CONCLUSION: We observed substantial pancreatic tumor motion during BH as well as considerable position variation between consecutive BHs on a single day. We recommend further quantifying these uncertainties before introducing breath-hold during radiation treatment of pancreatic cancer patients. Also, the diaphragm cannot be used as a surrogate for pancreatic tumor motion.

Differences in respiratory-induced pancreatic tumor motion between 4D treatment planning CT and daily cone beam CT, measured using intratumoral fiducials.

BACKGROUND: In radiotherapy, the magnitude of respiratory-induced tumor motion is often measured using a single four-dimensional computed tomography (4DCT). This magnitude is required to determine the internal target volume. The aim of this study was to compare the magnitude of respiratory-induced motion of pancreatic tumors on a single 4DCT with the motion on daily cone beam CT (CBCT) scans during a 3-5-week fractionated radiotherapy scheme. In addition, we investigated changes in the respiratory motion during the treatment course. MATERIAL AND METHODS: The mean peak-to-peak motion (i.e. magnitude of motion) of pancreatic tumors was measured for 18 patients using intratumoral gold fiducials visible on CBCT scans made prior to each treatment fraction (10-27 CBCTs per patient; 401 CBCTs in total). For each patient, these magnitudes were compared to the magnitude measured on 4DCT. Possible time trends were investigated by applying linear fits to the tumor motion determined from daily CBCTs as a function of treatment day. RESULTS: We found a significant (p ≤ 0.01) difference between motion magnitude on 4DCT and on CBCT in superior-inferior, anterior-posterior and left-right direction, in 13, 9 and 12 of 18 patients, respectively. In the anterior- posterior and left-right direction no fractions had a difference ≥ 5 mm. In the superior-inferior direction the difference was ≥ 5 mm for 17% of the 401 fractions. In this direction, a significant (p ≤ 0.05) time trend in tumor motion was observed in 4 of 18 patients, but all trends were small (- 0.17-0.10 mm/day) and did not explain the large differences in motion magnitude between 4DCT and CBCT. CONCLUSION: A single measurement of the respiratory-induced motion magnitude of pancreatic tumors using 4DCT is often not representative for the magnitude during daily treatment over a 3-5-week radiotherapy scheme. For this patient group it may be beneficial to introduce breath-hold to eliminate respiratory-induced tumor motion.

Stomach Motion and Deformation: Implications for Preoperative Gastric Cancer Radiation Therapy.

PURPOSE: Selection and development of image guided strategies for preoperative gastric radiation therapy requires quantitative knowledge of the various sources of anatomic changes of the stomach. This study aims to investigate the magnitude of interfractional and intrafractional stomach motion and deformation using fiducial markers and 4-dimensional (4D) imaging. METHODS AND MATERIALS: Fourteen patients who underwent preoperative gastric cancer radiation therapy received 2 to 6 fiducial markers distributed throughout the stomach (total of 54 markers) and additional imaging (ie, 1 planning 4D computed tomography [pCT], 20-25 pretreatment 4D cone beam [CB] CTs, 4-5 posttreatment 4D CBCTs). Marker coordinates on all end-exhale (EE) and end-inhale (EI) scans were obtained after a bony anatomy match. Interfractional marker displacements (ie, between EE pCT and all EE CBCTs) were evaluated for 5 anatomic regions (ie, cardia, small curvature, proximal and distal large curvature, and pylorus). Motion was defined as displacement of the center-of-mass of available markers (COMstomach), deformation as the average difference in marker-pair distances. Interfractional (ie, between EE pCT and all EE CBCTs), respiratory (between EE and EI pCT and CBCTs), and pre-post (pre- and posttreatment EE CBCTs) motion and deformation were quantified. RESULTS: The interfractional marker displacement varied per anatomic region and direction, with systematic and random errors ranging from 1.6-8.8 mm and 2.2-8.2 mm, respectively. Respiratory motion varied per patient (median, 3-dimensional [3D] amplitude 5.2-20.0 mm) and day (interquartile range, 0.8-4.2 mm). Regarding COMstomach motion, respiratory motion was larger than interfractional motion (median, 10.9 vs 8.9 mm; P < .0001; Wilcoxon rank-sum), which was larger than pre-post motion (3.6 mm; P < .0001). Interfractional deformations (median, 5.8 mm) were significantly larger than pre-post deformations (2.6 mm; P < .0001), which were larger than respiratory deformation (1.8 mm; P < .0001). CONCLUSIONS: The demonstrated sizable stomach motions and deformations during radiation therapy stress the need for generous nonuniform planning target volume margins for preoperative gastric cancer radiation therapy. These margins can be decreased by daily image guidance and adaptive radiation therapy.

Dosimetric benefit of a library of plans versus single-plan strategy for pre-operative gastric cancer radiotherapy.

BACKGROUND AND PURPOSE: The stomach experiences large volume and shape changes during pre-operative gastric radiotherapy. This study evaluates the dosimetric benefit for organs-at-risk (OARs) of a library of plans (LoP) compared to the traditional single-plan (SP) strategy. MATERIALS AND METHODS: Twelve patients who received SP CBCT-guided pre-operative gastric radiotherapy (45 Gy; 25 fractions) were included. Clinical target volume (CTV) consisted of CTVstomach (i.e., stomach + 10 mm uniform margin minus OARs) and CTVLN (i.e., regional lymph node stations). For LoP, five stomach volumes (approximately equidistant with fixed volumes) were created using a previously developed stomach deformation model (volume = 150-750 mL). Appropriate planning target volume (PTV) margins were calculated for CTVstomach (SP and LoP, separately) and CTVLN. Treatment plans were automatically generated/optimized and the best-fitting library plan was manually selected for each daily CBCT. OARs (i.e., liver, kidneys, heart, spleen, spinal canal) doses were accumulated and dose-volume histogram (DVH) parameters were evaluated. RESULTS: The non-isotropic PTVstomach margins were significantly (p < 0.05) smaller for LoP than SP (median = 13.1 vs 19.8 mm). For each patient, the average PTV was smaller using a LoP (difference range 134-1151 mL). For all OARs except the kidneys, DVH parameters were significantly reduced using a LoP. Differences in mean dose (Dmean) for liver, heart and spleen ranged between -1.8 to 5.7 Gy. For LoP, a benefit of heart Dmean > 4 Gy and spleen Dmean > 2 Gy was found in 4 and 5 patients, respectively. CONCLUSION: A LoP strategy for pre-operative gastric cancer reduced average PTV and reduced OAR dose compared to a SP strategy, thereby potentially reducing risks for radiation-induced toxicities.

Endoscopically placed fiducial markers for image-guided radiotherapy in preoperative gastric cancer: Technical feasibility and potential benefit.

Background and study aims Fiducial markers have demonstrated clinical value in radiotherapy in several organs, but little is known about markers in the stomach. Here, we assess the technical feasibility of endoscopic placement of markers in gastric cancer patients and their potential benefit for image-guided radiotherapy (IGRT). Patients and methods In this prospective feasibility study, 14 gastric cancer patients underwent endoscopy-guided gold (all patients) and liquid (7 patients) marker placements distributed throughout the stomach. Technical feasibility, procedure duration, and potential complications were evaluated. Assessed benefit for IGRT comprised marker visibility on acquired imaging (3-4 computed tomography [CT] scans and 19-25 cone-beam CTs [CBCTs] per patient) and lack of migration. Marker visibility was compared per marker type and location (gastroesophageal junction (i.e., junction/cardia), corpus (corpus/antrum/fundus), and pylorus). Results Of the 93 marker implantation attempts, 59 were successful, i.e., marker in stomach wall and present during entire 5-week radiotherapy course (2-6 successfully placed markers per patient), with no significant difference (Fisher's exact test; P >0.05) in success rate between gold (39/66=59%) and liquid (20/27=74%). Average procedure duration was 24.4 min (range 16-38). No procedure-related complications were reported. All successfully placed markers were visible on all CTs, with 81% visible on ≥95% of CBCTs. Five markers were poorly visible (on <75% of CBCTs), possibly due to small marker volume and peristaltic motion since all five were liquid markers located in the corpus. No migration was observed. Conclusions Endoscopic placement of fiducial markers in the stomach is technically feasible and safe. Being well visible and positionally stable, markers provide a potential benefit for IGRT.

Gastric deformation models for adaptive radiotherapy: Personalized vs population-based strategy.

BACKGROUND AND PURPOSE: To create a library of plans (LoP) for gastric cancer adaptive radiotherapy, accurate predictions of shape changes due to filling variations are essential. The ability of two strategies (personalized and population-based) to predict stomach shape based on filling was evaluated for volunteer and patient data to explore the potential for use in a LoP. MATERIALS AND METHODS: For 19 healthy volunteers, stomachs were delineated on MRIs with empty (ES), half-full (HFS) and full stomach (FS). For the personalized strategy, a deformation vector field from HFS to corresponding ES was acquired and extrapolated to predict FS. For the population-based strategy, the average deformation vectors from HFS to FS of 18 volunteers were applied to the HFS of the remaining volunteer to predict FS (leave-one-out principle); thus, predictions were made for each volunteer. Reversed processes were performed to predict ES. To validate, for seven gastric cancer patients, the volunteer population-based model was applied to their pre-treatment CT to predict stomach shape on 2-3 repeat CTs. For all predictions, volume was made equal to true stomach volume. RESULTS: FS predictions were satisfactory, with median Dice similarity coefficient (mDSC) of 0.91 (population-based) and 0.89 (personalized). ES predictions were poorer: mDSC = 0.82 for population-based; personalized strategy yielded unachievable volumes. Population-based shape predictions (both ES and FS) were comparable between patients (mDSC = 0.87) and volunteers (0.88). CONCLUSION: The population-based model outperformed the personalized model and demonstrated its ability in predicting filling-dependent stomach shape changes and, therefore, its potential for use in a gastric cancer LoP.

Power spectral analysis for optical trap stiffness calibration from high-speed camera position detection with limited bandwidth.

The use of camera imaging enables trap calibration for multiple particles simultaneously. For stiff traps, however, blur from image integration time affects the detected particle positions significantly. In this paper we use power spectral analysis to calibrate stiff optical traps, taking the effects of blur, aliasing and position detection error into account, as put forward by Wong and Halvorsen [Opt. Express 14, 12517 (2006)]. We find agreement with simultaneously obtained photodiode data and the expected relation of corner frequency fc with laser power, up to fc = 3.6 kHz for a Nyquist frequency of 1.25 kHz. Spectral analysis enables easy identification of the contribution of noise. We demonstrate the utility of our approach with simultaneous calibration of multiple holographic optical traps.

Feasibility of cone beam CT-guided library of plans strategy in pre-operative gastric cancer radiotherapy.

BACKGROUND AND PURPOSE: The stomach displays large anatomical changes in size, shape and position, which implies the need for plan adaptation for gastric cancer patients who receive pre-operative radiotherapy. We evaluated the feasibility and necessity of a CBCT-guided library of plans (LoP) strategy in gastric cancer radiotherapy. METHODS: Eight gastric cancer patients treated with 24-25 fractions of single-plan radiotherapy with daily CBCT imaging were included. The target was delineated on the pre-treatment CT and first 5 CBCTs to create a patient-specific LoP. Plan selections were performed by 12 observers in a training stage (2-3 CBCTs per patient) and an assessment stage (17 CBCTs per patient). The observers were asked to select the smallest plan that encompassed the target on the CBCT. A total of 136 plan selections were evaluated in the assessment stage. RESULTS: Delineations on CBCTs showed that in 90% of the 40 delineated fractions part of the CTV was outside the PTV based on the pre-treatment CT. At least two-thirds of the observers agreed on the selected plan in 65.2% and 70% of the fractions in the training stage and the assessment stage, respectively. For each patient, at least two different plans from the LoP were the most selected plan. CONCLUSION: A CBCT-guided patient-specific LoP strategy is feasible for gastric cancer patients, yielding good agreement in plan selections. Unless generous margins are used to avoid frequent geometric misses, it is likely that part of the target will be missed with single-plan radiotherapy.

Calibration of dynamic holographic optical tweezers for force measurements on biomaterials.

Holographic optical tweezers (HOTs) enable the manipulation of multiple traps independently in three dimensions in real time. Application of this technique to force measurements requires calibration of trap stiffness and its position dependence. Here, we determine the trap stiffness of HOTs as they are steered in two dimensions. To do this, we trap a single particle in a multiple-trap configuration and analyze the power spectrum of the laser deflection on a position-sensitive photodiode. With this method, the relative trap strengths can be determined independent of exact particle size, and high stiffnesses can be probed because of the high bandwidth of the photodiode. We find a trap stiffness for each of three HOT traps of kappa approximately 26 pN/microm per 100 mW of laser power. Importantly, we find that this stiffness remains constant within +/- 4% over 20 microm displacements of a trap. We also investigate the minimum step size achievable when steering a trap with HOTs, and find that traps can be stepped and detected within approximately 2 nm in our instrument, although there is an underlying position modulation of the traps of comparable scale that arises from SLM addressing. The independence of trap stiffness on steering angle over wide ranges and the nanometer positioning accuracy of HOTs demonstrate the applicability of this technique to quantitative study of force response of extended biomaterials such as cells or elastomeric protein networks.

Manipulating metal-oxide nanowires using counter-propagating optical line tweezers.

Semiconducting nanowires, such as ZnO and Si, are used in the fields of nanophotonics and nanoelectronics. Optical tweezers offer the promise of flexible positional control of such particles in a liquid, but so far this has been limited to either manipulation close to the surface, or to axial trapping of nanowires. We show the three-dimensional trapping of ZnO and silica-coated Si nanowires in counter-propagating line tweezers, and demonstrate translational and rotational in-plane manipulation, away from the surfaces. The high-refractive index particles investigated - ZnO wires (n~1.9) with varying lengths up to 20mum and 6-mum-long silica-coated Si wires (n =3.6) - could not be trapped in single-beam line traps. Opposite surface charges are used to fix the nanowires to a surface. Full translational and in-plane rotational control of semiconducting nanowires expands the possibilities to position individual wires in complex geometries significantly.

Comparing the dosimetric impact of interfractional anatomical changes in photon, proton and carbon ion radiotherapy for pancreatic cancer patients.

Radiotherapy using charged particles is characterized by a low dose to the surrounding healthy organs, while delivering a high dose to the tumor. However, interfractional anatomical changes can greatly affect the robustness of particle therapy. Therefore, we compared the dosimetric impact of interfractional anatomical changes (i.e. body contour differences and gastrointestinal gas volume changes) in photon, proton and carbon ion therapy for pancreatic cancer patients. In this retrospective planning study, photon, proton and carbon ion treatment plans were created for 9 patients. Fraction dose calculations were performed using daily cone-beam CT (CBCT) images. To this end, the planning CT was deformably registered to each CBCT; gastrointestinal gas volumes were delineated on the CBCTs and copied to the deformed CT. Fraction doses were accumulated rigidly. To compare planned and accumulated dose, dose-volume histogram (DVH) parameters of the planned and accumulated dose of the different radiotherapy modalities were determined for the internal gross tumor volume, internal clinical target volume (iCTV) and organs-at-risk (OARs; duodenum, stomach, kidneys, liver and spinal cord). Photon plans were highly robust against interfractional anatomical changes. The difference between the planned and accumulated DVH parameters for the photon plans was less than 0.5% for the target and OARs. In both proton and carbon ion therapy, however, coverage of the iCTV was considerably reduced for the accumulated dose compared with the planned dose. The near-minimum dose ([Formula: see text]) of the iCTV reduced with 8% for proton therapy and with 10% for carbon ion therapy. The DVH parameters of the OARs differed less than 3% for both particle modalities. Fractionated radiotherapy using photons is highly robust against interfractional anatomical changes. In proton and carbon ion therapy, such changes can severely reduce the dose coverage of the target.