Diaphragm and abdominal organ motion during radiotherapy: a comprehensive multicenter study in 189 children.

BACKGROUND: For accurate thoracic and abdominal radiotherapy, inter- and intrafractional geometrical uncertainties need to be considered to enable accurate margin sizes. We aim to quantify interfractional diaphragm and abdominal organ position variations, and intrafractional diaphragm motion in a large multicenter cohort of pediatric cancer patients (< 18 years). We investigated the correlation of interfractional position variations and intrafractional motion with age, and with general anesthesia (GA). METHODS: In 189 children (mean age 8.1; range 0.4-17.9 years) from six institutes, interfractional position variation of both hemidiaphragms, spleen, liver, left and right kidneys was quantified using a two-step registration. CBCTs were registered to the reference CT relative to the bony anatomy, followed by organ registration. We calculated the group mean, systematic and random errors (standard deviations Σ and σ, respectively) in cranial-caudal (CC), left-right and anterior-posterior directions. Intrafractional right hemidiaphragm motion was quantified using CBCTs on which the breathing amplitude, defined as the difference between end-inspiration and end-expiration peaks, was assessed (N = 79). We investigated correlations with age (Spearman's ρ), and differences in motion between patients treated with and without GA (N = 75; all < 5.5 years). RESULTS: Interfractional group means were largest in CC direction and varied widely between patients, with largest variations in the right hemidiaphragm (range -13.0-17.5 mm). Interfractional group mean of the left kidney showed a borderline significant correlation with age (p = 0.047; ρ = 0.17). Intrafractional right hemidiaphragm motion in patients ≥ 5.5 years (mean 10.3 mm) was significantly larger compared to patients < 5.5 years treated without GA (mean 8.3 mm) (p = 0.02), with smaller Σ and σ values. We found a significant correlation between breathing amplitude and age (p < 0.001; ρ = 0.43). Interfractional right hemidiaphragm position variations were significantly smaller in patients < 5.5 years treated with GA than without GA (p = 0.004), but intrafractional motion showed no significant difference. CONCLUSION: In this large multicenter cohort of children undergoing thoracic and abdominal radiotherapy, we found that interfractional position variation does not depend on age, but the use of GA in patients < 5.5 years showed smaller systematic and random errors. Furthermore, our results showed that breathing amplitude increases with age. Moreover, variations between patients advocate the need for a patient-specific margin approach.

Adverse late health outcomes among children treated with 3D radiotherapy techniques: Study design of the Dutch pediatric 3D-RT study.

BACKGROUND: Adverse late health outcomes after multimodal treatment for pediatric cancer are diverse and of prime interest. Currently available evidence and survivorship care guidelines are largely based on studies addressing side-effects of two dimensional planned radiotherapy. AIMS: The Dutch pediatric 3D-planned radiotherapy (3D-RT) study aims to gain insight in the long-term health outcomes among children who had radiotherapy in the 3D era. Here, we describe the study design, data-collection methods, and baseline cohort characteristics. METHODS AND RESULTS: The 3D-RT study represents an expansion of the Dutch Childhood Cancer Survivor study (DCCSS) LATER cohort, including pediatric cancer patients diagnosed during 2000-2012, who survived at least 5 years after initial diagnosis and 2 years post external beam radiotherapy. Individual cancer treatment parameters were obtained from medical files. A national infrastructure for uniform collection and archival of digital radiotherapy files (Computed Tomography [CT]-scans, delineations, plan, and dose files) was established. Health outcome information, including subsequent tumors, originated from medical records at the LATER outpatient clinics, and national registry-linkage. With a median follow-up of 10.9 (interquartile range [IQR]: 7.9-14.3) years after childhood cancer diagnosis, 711 eligible survivors were identified. The most common cancer types were Hodgkin lymphoma, medulloblastoma, and nephroblastoma. Most survivors received radiotherapy directed to the head/cranium only, the craniospinal axis, or the abdominopelvic region. CONCLUSION: The 3D-RT study will provide knowledge on the risk of adverse late health outcomes and radiation-associated dose-effect relationships. This information is valuable to guide follow-up care of childhood cancer survivors and to refine future treatment protocols.

Mesorectal shape variation in rectal cancer radiotherapy in prone position using a belly board.

BACKGROUND AND PURPOSE: In rectal cancer patients, radiotherapy in prone position using a belly board can reduce the dose to organs at risk. For this patient group we investigated inter-fraction shape variation of the mesorectal part of the clinical target volume (CTV) and determined planning target volume (PTV) margins. MATERIALS AND METHODS: Patients with rectal cancer receiving neoadjuvant (chemo)radiotherapy were eligible. For each patient a planning computed tomography (pCT) and five cone-beam CT (CBCT) scans were acquired in prone position using a belly board. The mesorectal CTV was delineated on all scans. Mesorectal shape variation was quantified relative to the pCT. PTV margins were derived locally and averaged for separate subregions of the mesorectal CTV. For each patient a total PTV was constructed using our clinical margins for mesorectal and lymph node CTVs. An artificial dose distribution conforming to this PTV was used to calculate the coverage for the mesorectal CTV using the CBCT delineations. RESULTS: In 19 rectal cancer patients the derived PTV margins were smallest in the upper-lateral region (6 mm) and largest in the upper-anterior region (16 mm). PTV margins for the upper-anterior region were larger for female patients (19 mm) compared to male patients (14 mm). Clinical margins for the total PTV were sufficient for a coverage of at least 97% of the mesorectal CTV for all patients. CONCLUSIONS: Mesorectal shape variation is heterogeneous and largest in the upper-anterior region, in rectal cancer patients irradiated in prone position and using a belly board.

In vivo dosimetry with an electronic portal imaging device for prostate cancer radiotherapy with an endorectal balloon.

Electronic portal imaging device-based in vivo dosimetry with a commercial product was performed for 10 prostate cancer patients treated with an air-filled endorectal balloon. With the conventional in vivo method the verification results were outside of our clinical acceptance criteria for all patients. The in aqua vivo method, originally developed for lung cancer treatments, proved to be a practical solution to this problem. On average the percentage of points within γ agreement of 3% and 3 mm significantly improved from 90.9% ±â€¯2.5% (1SD) for the conventional in vivo method to 99.0% ±â€¯1.0% (1SD) for the in aqua vivo method.

The TRENDY multi-center randomized trial on hepatocellular carcinoma - Trial QA including automated treatment planning and benchmark-case results.

BACKGROUND AND PURPOSE: The TRENDY trial is an international multi-center phase-II study, randomizing hepatocellular carcinoma (HCC) patients between transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT) with a target dose of 48-54 Gy in six fractions. The radiotherapy quality assurance (QA) program, including prospective plan feedback based on automated treatment planning, is described and results are reported. MATERIALS AND METHODS: Scans of a single patient were used as a benchmark case. Contours submitted by nine participating centers were compared with reference contours. The subsequent planning round was based on a single set of contours. A total of 20 plans from participating centers, including 12 from the benchmark case, 5 from a clinical pilot and 3 from the first study patients, were compared to automatically generated VMAT plans. RESULTS: For the submitted liver contours, Dice Similarity Coefficients (DSC) with the reference delineation ranged from 0.925 to 0.954. For the GTV, the DSC varied between 0.721 and 0.876. For the 12 plans on the benchmark case, healthy liver normal-tissue complication probabilities (NTCPs) ranged from 0.2% to 22.2% with little correlation between NCTP and PTV-D95% (R2 < 0.3). Four protocol deviations were detected in the set of 20 treatment plans. Comparison with co-planar autoVMAT QA plans revealed these were due to too high target dose and suboptimal planning. Overall, autoVMAT resulted in an average liver NTCP reduction of 2.2 percent point (range: 16.2 percent point to -1.8 percent point, p = 0.03), and lower doses to the healthy liver (p < 0.01) and gastrointestinal organs at risk (p < 0.001). CONCLUSIONS: Delineation variation resulted in feedback to participating centers. Automated treatment planning can play an important role in clinical trials for prospective plan QA as suboptimal plans were detected.

Clinical implementation of 3D printing in the construction of patient specific bolus for electron beam radiotherapy for non-melanoma skin cancer.

BACKGROUND AND PURPOSE: Creating an individualized tissue equivalent material build-up (i.e. bolus) for electron beam radiation therapy is complex and highly labour-intensive. We implemented a new clinical workflow in which 3D printing technology is used to create the bolus. MATERIAL AND METHODS: A patient-specific bolus is designed in the treatment planning system (TPS) and a shell around it is created in the TPS. The shell is printed and subsequently filled with silicone rubber to make the bolus. Before clinical implementation we performed a planning study with 11 patients to evaluate the difference in tumour coverage between the designed 3D-print bolus and the clinically delivered plan with manually created bolus. For the first 15 clinical patients a second CT scan with the 3D-print bolus was performed to verify the geometrical accuracy. RESULTS: The planning study showed that the V85% of the CTV was on average 97% (3D-print) vs 88% (conventional). Geometric comparison of the 3D-print bolus to the originally contoured bolus showed a high similarity (DSC=0.89). The dose distributions on the second CT scan with the 3D print bolus in position showed only small differences in comparison to the original planning CT scan. CONCLUSIONS: The implemented workflow is feasible, patient friendly, safe, and results in high quality dose distributions. This new technique increases time efficiency.

Portal dosimetry in wedged beams.

Portal dosimetry using electronic portal imaging devices (EPIDs) is often applied to verify high-energy photon beam treatments. Due to the change in photon energy spectrum, the resulting dose values are, however, not very accurate in the case of wedged beams if the pixel-to-dose conversion for the situation without wedge is used. A possible solution would be to consider a wedged beam as another photon beam quality requiring separate beam modeling of the dose calculation algorithm. The aim of this study was to investigate a more practical solution: to make aSi EPID-based dosimetry models also applicable for wedged beams without an extra commissioning effort of the parameters of the model. For this purpose two energy-dependent wedge multiplication factors have been introduced to be applied for portal images taken with and without a patient/phantom in the beam. These wedge multiplication factors were derived from EPID and ionization chamber measurements at the EPID level for wedged and nonwedged beams, both with and without a polystyrene slab phantom in the beam. This method was verified for an EPID dosimetry model used for wedged beams at three photon beam energies (6, 10, and 18 MV) by comparing dose values reconstructed in a phantom with data provided by a treatment planning system (TPS), as a function of field size, depth, and off-axis distance. Generally good agreement, within 2%, was observed for depths between dose maximum and 15 cm. Applying the new model to EPID dose measurements performed during ten breast cancer patient treatments with wedged 6 MV photon beams showed that the average isocenter underdosage of 5.3% was reduced to 0.4%. Gamma-evaluation (global 3%/3 mm) of these in vivo data showed an increase in percentage of points with γ ≤ 1 from 60.2% to 87.4%, while γmean reduced from 1.01 to 0.55. It can be concluded that, for wedged beams, the multiplication of EPID pixel values with an energy-dependent correction factor provides good agreement between dose values determined by an EPID and a TPS, indicating the usefulness of such a practical solution.

Time-resolved dosimetry using a pinpoint ionization chamber as quality assurance for IMRT and VMAT.

PURPOSE: To develop a method to verify the dose delivery in relation to the individual control points of intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) using an ionization chamber. In addition to more effective problem solving during patient-specific quality assurance (QA), the aim is to eventually map out the limitations in the treatment chain and enable a targeted improvement of the treatment technique in an efficient way. METHODS: Pretreatment verification was carried out for 255 treatment plans that included a broad range of treatment indications in two departments using the equipment of different vendors. In-house developed software was used to enable calculation of the dose delivery for the individual beamlets in the treatment planning system (TPS), for data acquisition, and for analysis of the data. The observed deviations were related to various delivery and measurement parameters such as gantry angle, field size, and the position of the detector with respect to the field edge to distinguish between error sources. RESULTS: The average deviation of the integral fraction dose during pretreatment verification of the planning target volume dose was -2.1% ± 2.2% (1 SD), -1.7% ± 1.7% (1 SD), and 0.0% ± 1.3% (1 SD) for IMRT at the Radboud University Medical Center (RUMC), VMAT (RUMC), and VMAT at the Wellington Blood and Cancer Centre, respectively. Verification of the dose to organs at risk gave very similar results but was generally subject to a larger measurement uncertainty due to the position of the detector at a high dose gradient. The observed deviations could be related to limitations of the TPS beam models, attenuation of the treatment couch, as well as measurement errors. The apparent systematic error of about -2% in the average deviation of the integral fraction dose in the RUMC results could be explained by the limitations of the TPS beam model in the calculation of the beam penumbra. CONCLUSIONS: This study showed that time-resolved dosimetry using an ionization chamber is feasible and can be largely automated which limits the required additional time compared to integrated dose measurements. It provides a unique QA method which enables identification and quantification of the contribution of various error sources during IMRT and VMAT delivery.

In aqua vivo EPID dosimetry.

PURPOSE: At the Netherlands Cancer Institute--Antoni van Leeuwenhoek Hospital in vivo dosimetry using an electronic portal imaging device (EPID) has been implemented for almost all high-energy photon treatments of cancer with curative intent. Lung cancer treatments were initially excluded, because the original back-projection dose-reconstruction algorithm uses water-based scatter-correction kernels and therefore does not account for tissue inhomogeneities accurately. The aim of this study was to test a new method, in aqua vivo EPID dosimetry, for fast dose verification of lung cancer irradiations during actual patient treatment. METHODS: The key feature of our method is the dose reconstruction in the patient from EPID images, obtained during the actual treatment, whereby the images have been converted to a situation as if the patient consisted entirely of water; hence, the method is termed in aqua vivo. This is done by multiplying the measured in vivo EPID image with the ratio of two digitally reconstructed transmission images for the unit-density and inhomogeneous tissue situation. For dose verification, a comparison is made with the calculated dose distribution with the inhomogeneity correction switched off. IMRT treatment verification is performed for each beam in 2D using a 2D γ evaluation, while for the verification of volumetric-modulated arc therapy (VMAT) treatments in 3D a 3D γ evaluation is applied using the same parameters (3%, 3 mm). The method was tested using two inhomogeneous phantoms simulating a tumor in lung and measuring its sensitivity for patient positioning errors. Subsequently five IMRT and five VMAT clinical lung cancer treatments were investigated, using both the conventional back-projection algorithm and the in aqua vivo method. The verification results of the in aqua vivo method were statistically analyzed for 751 lung cancer patients treated with IMRT and 50 lung cancer patients treated with VMAT. RESULTS: The improvements by applying the in aqua vivo approach are considerable. The percentage of γ values ≤1 increased on average from 66.2% to 93.1% and from 43.6% to 97.5% for the IMRT and VMAT cases, respectively. The corresponding mean γ value decreased from 0.99 to 0.43 for the IMRT cases and from 1.71 to 0.40 for the VMAT cases, which is similar to the accepted clinical values for the verification of IMRT treatments of prostate, rectum, and head-and-neck cancers. The deviation between the reconstructed and planned dose at the isocenter diminished on average from 5.3% to 0.5% for the VMAT patients and was almost the same, within 1%, for the IMRT cases. The in aqua vivo verification results for IMRT and VMAT treatments of a large group of patients had a mean γ of approximately 0.5, a percentage of γ values ≤1 larger than 89%, and a difference of the isocenter dose value less than 1%. CONCLUSIONS: With the in aqua vivo approach for the verification of lung cancer treatments (IMRT and VMAT), we can achieve results with the same accuracy as obtained during in vivo EPID dosimetry of sites without large inhomogeneities.

3D Dosimetric verification of volumetric-modulated arc therapy by portal dosimetry.

BACKGROUND AND PURPOSE: To demonstrate the feasibility of back-projection portal dosimetry for accurate 3D dosimetric verification of volumetric-modulated arc therapy (VMAT), pre-treatment as well as in vivo. MATERIALS AND METHODS: Several modifications to our existing approach were implemented to make the method applicable to VMAT: (i) gantry angle-resolved data acquisition, (ii) calculation of the patient transmission, (iii) compensation for detector 'flex' and (iv) 3D dose reconstruction and evaluation. RESULTS: Planned and EPID-(Electronic Portal Image Detector)-reconstructed dose distributions show good agreement for pre-treatment verification of two prostate, a stereotactic lung and a head-and-neck VMAT plan and for in vivo verification of VMAT treatments of prostate and lung cancer. Averaged over pre-treatment verifications, planned and measured isocentre dose ratios were -1.2% (range [-4.7%,1.8%]). 3D gamma analysis (3% maximum dose, 3mm) revealed mean gamma gamma(mean)=0.37 [0.34,0.39], maximum 1% gamma gamma(1%)=0.72 [0.66,0.81] and percentage of points with gamma1 P(gamma)(1)=99% [97%,100%]. For in vivo verification, the average isocentre dose ratio was -1.2% [-0.8%,-1.7%], gamma(mean)=0.52 [0.40,0.64], gamma(1%)=0.92 [0.76,1.08] and P(gamma)(1)=96% [93%,100%]. CONCLUSIONS: Our portal dosimetry method was successfully adapted for verification of VMAT treatments, pre-treatment as well as in vivo.

A simple backprojection algorithm for 3D in vivo EPID dosimetry of IMRT treatments.

Treatment plans are usually designed, optimized, and evaluated based on the total 3D dose distribution, motivating a total 3D dose verification. The purpose of this study was to develop a 2D transmission-dosimetry method using an electronic portal imaging device (EPID) into a simple 3D method that provides 3D dose information. In the new method, the dose is reconstructed within the patient volume in multiple planes parallel to the EPID for each gantry angle. By summing the 3D dose grids of all beams, the 3D dose distribution for the total treatment fraction is obtained. The algorithm uses patient contours from the planning CT scan but does not include tissue inhomogeneity corrections. The 3D EPID dosimetry method was tested for IMRT fractions of a prostate, a rectum, and a head-and-neck cancer patient. Planned and in vivo-measured dose distributions were within 2% at the dose prescription point. Within the 50% isodose surface of the prescribed dose, at least 97% of points were in agreement, evaluated with a 3D gamma method with criteria of 3% of the prescribed dose and 0.3 cm. Full 3D dose reconstruction on a 0.1 x 0.1 x 0.1 cm3 grid and 3D gamma evaluation took less than 15 min for one fraction on a standard PC. The method allows in vivo determination of 3D dose-volume parameters that are common in clinical practice. The authors conclude that their EPID dosimetry method is an accurate and fast tool for in vivo dose verification of IMRT plans in 3D. Their approach is independent of the treatment planning system and provides a practical safety net for radiotherapy.

A literature review of electronic portal imaging for radiotherapy dosimetry.

Electronic portal imaging devices (EPIDs) have been the preferred tools for verification of patient positioning for radiotherapy in recent decades. Since EPID images contain dose information, many groups have investigated their use for radiotherapy dose measurement. With the introduction of the amorphous-silicon EPIDs, the interest in EPID dosimetry has been accelerated because of the favourable characteristics such as fast image acquisition, high resolution, digital format, and potential for in vivo measurements and 3D dose verification. As a result, the number of publications dealing with EPID dosimetry has increased considerably over the past approximately 15 years. The purpose of this paper was to review the information provided in these publications. Information available in the literature included dosimetric characteristics and calibration procedures of various types of EPIDs, strategies to use EPIDs for dose verification, clinical approaches to EPID dosimetry, ranging from point dose to full 3D dose distribution verification, and current clinical experience. Quality control of a linear accelerator, pre-treatment dose verification and in vivo dosimetry using EPIDs are now routinely used in a growing number of clinics. The use of EPIDs for dosimetry purposes has matured and is now a reliable and accurate dose verification method that can be used in a large number of situations. Methods to integrate 3D in vivo dosimetry and image-guided radiotherapy (IGRT) procedures, such as the use of kV or MV cone-beam CT, are under development. It has been shown that EPID dosimetry can play an integral role in the total chain of verification procedures that are implemented in a radiotherapy department. It provides a safety net for simple to advanced treatments, as well as a full account of the dose delivered. Despite these favourable characteristics and the vast range of publications on the subject, there is still a lack of commercially available solutions for EPID dosimetry. As strategies evolve and commercial products become available, EPID dosimetry has the potential to become an accurate and efficient means of large-scale patient-specific IMRT dose verification for any radiotherapy department.

3D in vivo dose verification of entire hypo-fractionated IMRT treatments using an EPID and cone-beam CT.

As radiotherapy becomes more complicated, dose and geometry verification become more necessary. The aim of this study was to use back-projected EPID-based 3D in vivo dosimetry and cone-beam CT (CBCT) to obtain a complete account of the entire treatment for a select patient group. Nine hypo-fractionated rectum IMRT patient plans were investigated. The absolute dose was reconstructed at multiple planes using patient contours and EPID images acquired for all fields during treatment. The meso-rectal fat (m-R) was re-delineated on daily CBCT scans, acquired prior to each fraction. The total accumulated dose was determined by mapping the m-R surface of each fraction to the planned m-R surface. Average planned and measured isocentre dose ratios were 0.98 (+/-0.01SD). 3D gamma analysis (3% maximum dose and 3mm) revealed mean gamma, gamma(mean)=0.35 (+/-0.03 SD), maximum 1% of gamma points, gamma(max1%)=1.02 (+/-0.14SD) and the percentage of points with gamma < or = 1, P(gamma < or = 1)=99% (range [96%, 100%]), averaged over all patients. CBCT m-R volumes varied by up to 20% of planned volumes, but remained in the high dose region. Over-dosage of up to 4.5% in one fraction was measured in the presence of gas pockets. By combining EPID dosimetry with CBCT geometry information, the total dose can be verified in 3D in vivo and compared with the planned dose distribution. This method can provide a safety net for advanced treatments involving dose escalation, as well as a full account of the delivered dose to specific volumes, allowing adaptation of the treatment from the original plan if necessary.

A fast algorithm for gamma evaluation in 3D.

The gamma-evaluation method is a tool by which dose distributions can be compared in a quantitative manner combining dose-difference and distance-to-agreement criteria. Since its introduction, the gamma evaluation has been used in many studies and is on the verge of becoming the preferred dose distribution comparison method, particularly for intensity-modulated radiation therapy (IMRT) verification. One major disadvantage, however, is its long computation time, which especially applies to the comparison of three-dimensional (3D) dose distributions. We present a fast algorithm for a full 3D gamma evaluation at high resolution. Both the reference and evaluated dose distributions are first resampled on the same grid. For each point of the reference dose distribution, the algorithm searches for the best point of agreement according to the gamma method in the evaluated dose distribution, which can be done at a subvoxel resolution. Speed, computer memory efficiency, and high spatial resolution are achieved by searching around each reference point with increasing distance in a sphere, which has a radius of a chosen maximum search distance and is interpolated "on-the-fly" at a chosen sample step size. The smaller the sample step size and the larger the differences between the dose distributions, the longer the gamma evaluation takes. With decreasing sample step size, statistical measures of the 3D gamma distribution converge. Two clinical examples were investigated using 3% of the prescribed dose as dose-difference and 0.3 cm as distance-to-agreement criteria. For 0.2 cm grid spacing, the change in gamma indices was negligible below a sample step size of 0.02 cm. Comparing the full 3D gamma evaluation and slice-by-slice 2D gamma evaluations ("2.5D") for these clinical examples, the gamma indices improved by searching in full 3D space, with the average gamma index decreasing by at least 8%.

Replacing pretreatment verification with in vivo EPID dosimetry for prostate IMRT.

PURPOSE: To investigate the feasibility of replacing pretreatment verification with in vivo electronic portal imaging device (EPID) dosimetry for prostate intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Dose distributions were reconstructed from EPID images, inside a phantom (pretreatment) or the patient (five fractions in vivo) for 75 IMRT prostate plans. Planned and EPID dose values were compared at the isocenter and in two dimensions using the gamma index (3%/3 mm). The number of measured in vivo fractions required to achieve similar levels of agreement with the plan as pretreatment verification was determined. The time required to perform both methods was compared. RESULTS: Planned and EPID isocenter dose values agreed, on average, within +/-1% (1 SD) of the total plan for both pretreatment and in vivo verification. For two-dimensional field-by-field verification, an alert was raised for 10 pretreatment checks with clear but clinically irrelevant discrepancies. Multiple in vivo fractions were combined by assessing gamma images consisting of median, minimum and low (intermediate) pixel values of one to five fractions. The "low" gamma values of three fractions rendered similar results as pretreatment verification. Additional time for verification was approximately 2.5 h per plan for pretreatment verification, and 15 min +/- 10 min/fraction using in vivo dosimetry. CONCLUSIONS: In vivo EPID dosimetry is a viable alternative to pretreatment verification for prostate IMRT. For our patients, combining information from three fractions in vivo is the best way to distinguish systematic errors from non-clinically relevant discrepancies, save hours of quality assurance time per patient plan, and enable verification of the actual patient treatment.

Anatomy changes in radiotherapy detected using portal imaging.

BACKGROUND AND PURPOSE: Localisation images normally acquired to verify patient positioning also contain information about the patient's internal anatomy. The aim of this study was to investigate the anatomical changes observed in localisation images and examples of dosimetric consequences. PATIENTS AND METHODS: Localisation images were obtained weekly prior to radiotherapy with an electronic portal imaging device (EPID). A series of 'difference images' was created by subtracting the first localisation image from that of subsequent fractions. Images from 81 lung, 40 head and neck and 34 prostate cancer patients were classified according to the changes observed. Changes were considered relevant if the average pixel value over an area of at least 1cm(2) differed by more than 5%, to allow for variations in linac output and EPID signal. Two patients were selected to illustrate the dosimetric effects of relevant changes. Their plans were re-calculated with repeat CT scans acquired after 4 weeks of treatment and compared with the difference images of the corresponding days. RESULTS: Progressive changes were detected for 57% of lung and 37% of head and neck cancer patients studied. Random changes were observed in 37% of lung, 28% of head and neck and 82% of prostate cancer patients. For a lung case, an increase of 10.0% in EPID dose due to tumour shrinkage corresponded to an increase of 9.8% in mean lung dose. Gas pockets in the rectum region of the prostate case increased the EPID dose by 6.3%, and resulted in a decrease of the minimum dose to the planning target volume of 26.4%. CONCLUSIONS: Difference images are an efficient means of qualitatively detecting anatomical changes for various treatment sites in clinical practice. They can be used to identify changes for a particular patient, to indicate if the dose delivered to the patient would differ from planning and to detect if there is a need for re-planning.

Accurate two-dimensional IMRT verification using a back-projection EPID dosimetry method.

The use of electronic portal imaging devices (EPIDs) is a promising method for the dosimetric verification of external beam, megavoltage radiation therapy-both pretreatment and in vivo. In this study, a previously developed EPID back-projection algorithm was modified for IMRT techniques and applied to an amorphous silicon EPID. By using this back-projection algorithm, two-dimensional dose distributions inside a phantom or patient are reconstructed from portal images. The model requires the primary dose component at the position of the EPID. A parametrized description of the lateral scatter within the imager was obtained from measurements with an ionization chamber in a miniphantom. In addition to point dose measurements on the central axis of square fields of different size, we also used dose profiles of those fields as reference input data for our model. This yielded a better description of the lateral scatter within the EPID, which resulted in a higher accuracy in the back-projected, two-dimensional dose distributions. The accuracy of our approach was tested for pretreatment verification of a five-field IMRT plan for the treatment of prostate cancer. Each field had between six and eight segments and was evaluated by comparing the back-projected, two-dimensional EPID dose distribution with a film measurement inside a homogeneous slab phantom. For this purpose, the y-evaluation method was used with a dose-difference criterion of 2% of dose maximum and a distance-to-agreement criterion of 2 mm. Excellent agreement was found between EPID and film measurements for each field, both in the central part of the beam and in the penumbra and low-dose regions. It can be concluded that our modified algorithm is able to accurately predict the dose in the midplane of a homogeneous slab phantom. For pretreatment IMRT plan verification, EPID dosimetry is a reliable and potentially fast tool to check the absolute dose in two dimensions inside a phantom for individual IMRT fields. Film measurements inside a phantom can therefore be replaced by EPID measurements.

Low-intensity pump-probe measurements on the B800 band of Rhodospirillum molischianum.

We have measured low-intensity, polarized one-color pump-probe traces in the B800 band of the light-harvesting complex LH2 of Rhodospirillum molischianum at 77 K. The excitation/detection wavelength was tuned through the B800 band. A single-wavelength and a global target analysis of the data were performed with a model that accounts for excitation energy transfer among the B800 molecules and from B800 to B850. By including the anisotropy of the signals into the fitting procedure, both transfer processes could be separated. It was estimated in the global target analysis that the intra-B800 energy transfer, i.e., the hopping of the excitation from one B800 to another B800 molecule, takes approximately 0.5 ps at 77 K. This transfer time increases with the excitation/detection wavelength from 0.3 ps on the blue side of the B800 band to approximately 0.8 ps on the red side. The residual B800 anisotropy shows a wavelength dependence as expected for energy transfer within an inhomogeneously broadened cluster of weakly coupled pigments. In the global target analysis, the transfer time from B800 to B850 was determined to be approximately 1.7 ps at 77 K. In the single-wavelength analysis, a speeding-up of the B800 --> B850 energy transfer rate toward the blue edge of the B800 band was found. This nicely correlates with the proposed position of the suggested high-exciton component of the B850 band acting as an additional decay channel for B800 excitations.

The quantitative relationship between structure and polarized spectroscopy in the FMO complex of Prosthecochloris aestuarii: refining experiments and simulations.

New absorption, linear dichroism (LD) and circular dichroism (CD) measurements at low temperatures on the Fenna-Matthews-Olson complex from Prosthecochloris aestuarii are presented. Furthermore, the anisotropy of fluorescence excitation spectra is measured and used to determine absolute LD spectra, i.e. corrected for the degree of orientation of the sample. In contrast to previous studies, this allows comparison of not only the shape but also the amplitude of the measured spectra with that calculated by means of an exciton model. In the exciton model, the point-dipole approximation is used and the calculations are based on the trimeric structure of the complex. An improved description of the absorption and LD spectra by means of the exciton model is obtained by simply using the same site energies and coupling strengths that were given by Louwe et al. (1997, J Phys Chem B 101: 11280-11287) and including three broadening mechanisms, which proved to be essential: Inhomogeneous broadening in a Monte Carlo approach, homogeneous broadening by using the homogeneous line shape determined by fluorescence line-narrowing measurements [Wendling et al. (2000) J Phys Chem B 104: 5825-5831] and lifetime broadening. An even better description is obtained when the parameters are optimized by a global fit of the absorption, LD and CD spectra. New site energies and coupling strengths are estimated. The amplitude of the LD spectrum is described quite well. The shape of the CD spectrum is modelled in a satisfactory way but its size can only be simulated by using a rather large value for the index of refraction of the medium surrounding the chromophores. It is shown that the estimated coupling strengths are compatible with the value of the dipole strength of bacteriochlorophyll a, when using the empty-cavity model for the local-field correction factor.