Impact of high dose volumetric CT on PTV margin reduction in VMAT prostate radiotherapy.

The aim of the study is to determine PTV margin for inter-observer variability in the volumetric modulated arc therapy (VMAT) prostate radiotherapy with high-dose volumetric CT (HDVCT) and conventional helical CT (CCT) for planning. Secondly to investigate the impact of geometric (PTV expansion) and dosimetric (conformity) imperfection of planning process on the PTV margin analysis. Prostate gland of ten patients were scanned with CCT and HDVCT techniques consecutively on a 320 slice volumetric CT scanner with wide field detector of 16 cm. Five radiation oncologists delineated CTV of the prostate. VMAT plans were developed with PTV margin of 4 mm and 6 mm (totaling 200 plans) and target coverage of each plan was evaluated on the target volume in agreement determined by shared voxels with three or more from 5 observers. Dosimetry on 200 VMAT plans showed that PTV margin for inter-observer variability were 6 mm and 4 mm for CCT and HDVCT techniques, respectively. It is about 3 mm smaller than our estimation from the previous study (8.8 mm and 7.3 mm) based on the inter-observer variability. This difference is mainly due to the accuracy of PTV volume expansion and limited dose conformity to guarantee target coverage. PTVs were measured 2 mm larger on average than the assigned margin. Planning iso-dose volume was found to be 2 mm larger than PTV. Regardless these limitations, enhanced image quality of HDVCT reduces PTV margin by 2 mm compared to CCT. PTV reduction of 2 mm potentially leads to 15% reduction in D30% of rectal and bladder wall maintaining the same target coverage. Inter-observer variability remains a source of systematic uncertainty. HDVCT for treatment planning demonstrated reduction of the uncertainty and the PTV margin by 2 mm. It is important to consider the over-expanded PTV volume and generous iso-dose volume after optimization in the process of radiotherapy planning in the determination of PTV margin.

A randomized comparison of interfraction and intrafraction prostate motion with and without abdominal compression.

BACKGROUND AND PURPOSE: To quantify inter- and intrafraction prostate motion in a standard VacLok (VL) immobilization device or in the BodyFix (BF) system incorporating a compression element which may reduce abdominal movement. MATERIALS AND METHODS: Thirty-two patients were randomly assigned to VL or BF. Interfraction prostate motion >3 mm was corrected pre-treatment. EPIs were taken daily at the start and end of the first and last treatment beams. Interfraction and intrafraction prostate motion were measured for centre of mass (COM) and individual markers. RESULTS: There were no significant differences in interfraction (p0.002) or intrafraction (p0.16) prostate motion with or without abdominal compression. Median intrafraction motion was slightly smaller than interfraction motion in the AP (7.0 mm vs. 7.6 mm) and SI direction (3.2 mm vs. 4.7 mm). The final image captured the maximal intrafraction displacement in only 40% of fractions. Our PTV incorporated >95% of total prostate motion. CONCLUSIONS: Intrafraction motion became the major source of error during radiotherapy after online correction of interfraction prostate motion. The addition of 120 mbar abdominal compression to custom pelvic immobilization influenced neither interfraction nor intrafraction prostate motion.

Studies of the in vivo radiosensitivity of human skin fibroblasts.

BACKGROUND AND PURPOSE: To examine the radiosensitivity of skin cells obtained directly from the irradiated skin of patients undergoing fractionated radiation treatment prior to surgery for treatment of soft tissue sarcoma (STS) and to determine if there was a relationship with the development of wound healing complications associated with the surgery post-radiotherapy. METHODS: Micronucleus (MN) formation was measured in cells (primarily dermal fibroblasts) obtained from human skin at their first division after being removed from STS patients during post-radiotherapy surgery (2-9 weeks after the end of the radiotherapy). At the time of radiotherapy (planned tumor dose - 50Gy in 25 daily fractions) measurements were made of surface skin dose at predetermined marked sites. Skin from these sites was obtained at surgery and cell suspensions were prepared directly for the cytokinesis-blocked MN assay. Cultured strains of the fibroblasts were also established from skin nominally outside the edge of the radiation beam and DNA damage (MN formation) was examined following irradiation in vitro for comparison with the results from the in situ irradiations. RESULTS: Extensive DNA damage (MN) was detectable in fibroblasts from human skin at extended periods after irradiation (2-9 weeks after the end of the 5-week fractionated radiotherapy). Analysis of skin receiving a range of doses demonstrated that the level of damage observed was dose dependent. There was no clear correlation between the level of damage observed after irradiation in situ and irradiation of cell strains in culture. Similarly, there was no correlation between the extent of MN formation following in situ irradiation and the propensity for the patient to develop wound healing complications post-surgery. CONCLUSIONS: Despite the presence of DNA damage in dermal fibroblasts weeks after the end of the radiation treatment, there was no relationship between this damage and wound healing complications following surgery post-irradiation. These results suggest that factors other than the radiosensitivity of the skin fibroblasts likely also play a role in wound healing in deep wound sites associated with surgery for STS following radiation therapy.

Investigation of the dosimetric effect of respiratory motion using four-dimensional weighted radiotherapy.

We have developed a four-dimensional weighted radiotherapy (4DW-RT) technique. This method involves designing the motion of the linear accelerator beam to coincide with the tumour motion determined from 4D-CT imaging while including a weighting factor to account for irregular motion and limitations of the delivery system. Experiments were conducted with a moving phantom to assess limitations of the delivery system when applying this method. Although the multi-leaf collimator motion remains within the tolerance of the linear accelerator, the extent of motion was less than 1 mm larger than the designed one, and there was a net system latency of approximately 0.2 s. The dose distributions were measured and simulated using different weighting factors and motion scenarios. The breathing characteristics (period, extent of motion, drift and standard deviations) of 32 patients were evaluated using the Varian RPM system. Breathing variability was assessed by plotting the average breathing motion as a function of the breathing phase. Simulations were carried out to determine the optimal weighting factor based on typical patient breathing characteristics. These results establish that the 4DW-RT method demonstrates potential for dose escalation without increasing exposure to healthy tissue.

'Compromise position' image alignment to accommodate independent motion of multiple clinical target volumes during radiotherapy: A high risk prostate cancer example.

INTRODUCTION: Inclusion of multiple independently moving clinical target volumes (CTVs) in the irradiated volume causes an image guidance conundrum. The purpose of this research was to use high risk prostate cancer as a clinical example to evaluate a 'compromise' image alignment strategy. METHODS: The daily pre-treatment orthogonal EPI for 14 consecutive patients were included in this analysis. Image matching was performed by aligning to the prostate only, the bony pelvis only and using the 'compromise' strategy. Residual CTV surrogate displacements were quantified for each of the alignment strategies. RESULTS: Analysis of the 388 daily fractions indicated surrogate displacements were well-correlated in all directions (r2  = 0.95 (LR), 0.67 (AP) and 0.59 (SI). Differences between the surrogates displacements (95% range) were -0.4 to 1.8 mm (LR), -1.2 to 5.2 mm (SI) and -1.2 to 5.2 mm (AP). The distribution of the residual displacements was significantly smaller using the 'compromise' strategy, compared to the other strategies (p 0.005). The 'compromise' strategy ensured the CTV was encompassed by the PTV in all fractions, compared to 47 PTV violations when aligned to prostate only. CONCLUSIONS: This study demonstrated the feasibility of a compromise position image guidance strategy to accommodate simultaneous displacements of two independently moving CTVs. Application of this strategy was facilitated by correlation between the CTV displacements and resulted in no geometric excursions of the CTVs beyond standard sized PTVs. This simple image guidance strategy may also be applicable to other disease sites that concurrently irradiate multiple CTVs, such as head and neck, lung and cervix cancer.

Evaluation of high dose volumetric CT to reduce inter-observer delineation variability and PTV margins for prostate cancer radiotherapy.

PURPOSE: The aim was to determine whether the enhanced soft tissue contrast provided by high-dose volumetric CT (HDVCT) can reduce inter-observer variability in delineating prostate compared to helical conventional CT (CCT) scans and 3T MRI scans for patients undergoing radical prostate cancer radiotherapy. Secondly, to quantify the potential PTV reduction with decreased inter-observer variability. MATERIALS AND METHODS: A 320 slice volumetric CT scanner was used. The wide-detector coverage of 16cm enabled volumetric image acquisition of prostate gland in one rotation. Three imaging studies were performed on ten patients. CCT and HDVCT were performed consecutively at the same coordinate system followed by MRI. Five radiation oncologists delineated the prostate. RESULTS: The inter-observer variability is 2.0±0.6, 1.9±0.4 and 1.8±0.4mm for CCT, HDVCT and MR respectively with the maximum at the apex region. Comparing inter-observer difference variability between CCT and HDVCT with MR indicates that observers have larger variations in contouring using CCT than HDVCT especially at apex. Jaccard index of HDVCT is significantly higher than CCT with a mean difference of 0.03 (p=0.011). Both MRI and HDVCT provide the opportunity for a 2mm PTV margin reduction at the apex compared to CCT. CONCLUSION: Inter-observer variability in delineation remains an important source of systematic error. HDCTV for treatment planning reduces this error without recourse to MRI and permits a PTV reduction of 2mm at the apex. The margins required to account for residual error with any imaging modality are still greater than are used in typical current practice.

Patient dose from kilovoltage cone beam computed tomography imaging in radiation therapy.

Kilovoltage cone-beam computerized tomography (kV-CBCT) systems integrated into the gantry of linear accelerators can be used to acquire high-resolution volumetric images of the patient in the treatment position. Using on-line software and hardware, patient position can be determined accurately with a high degree of precision and, subsequently, set-up parameters can be adjusted to deliver the intended treatment. While the patient dose due to a single volumetric imaging acquisition is small compared to the therapy dose, repeated and daily image guidance procedures can lead to substantial dose to normal tissue. The dosimetric properties of a clinical CBCT system have been studied on an Elekta linear accelerator (Synergy RP, XVI system) and additional measurements performed on a laboratory system with identical geometry. Dose measurements were performed with an ion chamber and MOSFET detectors at the center, periphery, and surface of 30 and 16-cm-diam cylindrical shaped water phantoms, as a function of x-ray energy and longitudinal field-of-view (FOV) settings of 5,10,15, and 26 cm. The measurements were performed for full 360 degrees CBCT acquisition as well as for half-rotation scans for 120 kVp beams using the 30-cm-diam phantom. The dose at the center and surface of the body phantom were determined to be 1.6 and 2.3 cGy for a typical imaging protocol, using full rotation scan, with a technique setting of 120 kVp and 660 mAs. The results of our measurements have been presented in terms of a dose conversion factor fCBCT, expressed in cGy/R. These factors depend on beam quality and phantom size as well as on scan geometry and can be utilized to estimate dose for any arbitrary mAs setting and reference exposure rate of the x-ray tube at standard distance. The results demonstrate the opportunity to manipulate the scanning parameters to reduce the dose to the patient by employing lower energy (kVp) beams, smaller FOV, or by using half-rotation scan.

On-line aSi portal imaging of implanted fiducial markers for the reduction of interfraction error during conformal radiotherapy of prostate carcinoma.

PURPOSE: An on-line system to ensure accuracy of daily setup and therapy of the prostate has been implemented with no equipment modification required. We report results and accuracy of patient setup using this system. METHODS AND MATERIALS: Radiopaque fiducial markers were implanted into the prostate before radiation therapy. Lateral digitally reconstructed radiographs (DRRs) were obtained from planning CT data. Before each treatment fraction, a lateral amorphous silicon (aSi) portal image was acquired and the position of the fiducial markers was compared to the DRRs using chamfer matching. Couch translation only was used to account for marker position displacements, followed by a second lateral portal image to verify isocenter position. Residual displacement data for the aSi and previous portal film systems were compared. RESULTS: This analysis includes a total of 239 portal images during treatment in 17 patients. Initial prostate center of mass (COM) displacements in the superior, inferior, anterior, and posterior directions were a maximum of 7 mm, 9 mm, 10 mm and 11 mm respectively. After identification and correction, prostate COM displacements were <3 mm in all directions. The therapists found it simple to match markers 88% of the time using this system. Treatment delivery times were in the order of 9 min for patients requiring isocenter adjustment and 6 min for those who did not. CONCLUSIONS: This system is technically possible to implement and use as part of an on-line correction protocol and does not require a longer than standard daily appointment time at our center with the current action limit of 3 mm. The system is commercially available and is more efficient and user-friendly than portal film analysis. It provides the opportunity to identify and accommodate interfraction organ motion and may also permit the use of smaller margins during conformal prostate radiotherapy. Further integration of the system such as remote table control would improve efficiency.

A randomized trial of supine vs. prone positioning in patients undergoing escalated dose conformal radiotherapy for prostate cancer.

BACKGROUND AND PURPOSE: The optimal treatment position for patients receiving radical radiation therapy for prostate cancer has been a source of controversy. To resolve this issue, we conducted a randomized trial to evaluate the effects of supine and prone positioning on organ motion, positioning errors, and dose to critical organs during escalated dose conformal irradiation for localized prostate cancer and patient and therapist satisfaction with setup technique. PATIENTS AND METHODS: Twenty eight patients were randomized to commence treatment immobilized in the supine or prone position and were subsequently changed to the alternate positioning for the latter half of their treatment. Patients underwent CT simulation and conformal radiotherapy planning and treatment in both positions. The clinical target volume encompassed the prostate gland. Alternate day lateral port films were compared to corresponding simulator radiographs to measure the isocentre positioning errors (IPE). Prostate motion (PM) and total positioning error (TPE) were measured from the same films by the displacements of three implanted fiducial markers. Dose volume histograms (DVHs) for the two treatment positions were compared at the 95, 80 and 50% dose (D%) levels. The patients and radiation therapists completed weekly questionnaires regarding patient comfort and ease of setup. RESULTS: Seven patients, who started in the supine position, subsequently refused prone position and received their whole treatment supine. Small bowel in the treatment volume, not present in the supine position, prevented one patient from being treated prone. PM in anterior posterior direction was statistically significantly less in the supine position (P<0.05). There was no significant difference in superior inferior PM for the two treatment positions. No statistically significant difference between supine and prone positioning was observed in isocentre positioning error (IPE) or total positioning error (TPE) due to a policy of daily pre-treatment correction. However, more pre-treatment corrections were required for patients in the prone position. The DVH analysis demonstrated larger volumes of the bladder wall, rectal wall and small bowel within the D95, D80 and D50% when comparing the planning target volumes (PTVs) actually treated for prone positioning. When the prone PTV was expanded to account for the greater PM encountered in that position, a statistically significant difference (P<0.007) was observed in favour of the supine position at all dose levels. In the prone position, four patients had small bowel within the 60 Gray (Gy) isodose and in the supine position, no patients had small bowel in the 60 or 38Gy volumes. Supine position was significantly more comfortable for the patients and setup was significantly easier for the radiation therapists. The median patient comfort score was 0.79 (Standard deviation (SD) 0.03) supine and 0.45 (SD 0.05) prone (P<0.001) The therapist convenience of setup was 0.80 (SD 0.016) supine and 0.54 (SD 0.025) prone (P<0.005). No statistically significant difference was seen for the other parameters studied. CONCLUSIONS: We demonstrated significantly less PM in the supine treatment position. There was no difference for either treatment position in IPE or TPE, however, more pre-treatment corrections were required in the prone position. Prone position required a larger PTV with resulting increased dose to critical organs. There were statistically significant improvements at all dose levels for small bowel, rectal wall and bladder wall doses in the supine position once corrections were made for differences in organ motion. Linear analogue scores of patient comfort and radiation therapist convenience demonstrated statistically significant improvement in favour of the supine position. Supine positioning has been adopted as the standard for conformal prostatic irradiation at our centre.

A dose-volume histogram analysis of the seminal vesicles in men treated with conformal radiotherapy to 'prostate alone'.

BACKGROUND AND PURPOSE: There is no consensus on whether the seminal vesicles should be included in the clinical target volume (CTV) for radiotherapy of localized prostate cancer. To inform the debate, we have undertaken a dose-volume histogram (DVH) analysis of the seminal vesicles in patients treated with escalated dose conformal radiation to 'prostate alone'. MATERIAL AND METHODS: Twenty-five consecutive patients receiving conformal radiation to the prostate, to a dose of 75.6 Gy in 42 daily fractions, were studied. The CTV was defined as the prostate only, and the planning target volume (PTV) was defined by a 10 mm margin, except posteriorly where the margin was 7 mm. DVHs were calculated for the entire seminal vesicles, and for 6 mm segments through the seminal vesicles. RESULTS: Incorporating a correction for organ motion, the D90 (minimum dose received by 90% of the volume of interest) for the most inferior 6 mm volume of the seminal vesicles (SV1) ranged from 25 to 70 Gy, and the percentage volume of SV1 receiving 50 Gy ranged from 47-100%. Using a D90 of 50 Gy as a cut-off, eight of the 25 patients had unacceptably low-dose coverage of SV1. CONCLUSIONS: Escalated dose conformal radiation to the 'prostate alone' does not ensure adequate dose coverage of even the most inferior 6 mm of the seminal vesicles. We consider such treatment acceptable in patients at low risk of seminal vesicle involvement (T1/2ab, Gleason < or = 7, PSA < 10 ng/ml). In higher risk patients, if it is deemed necessary to treat the possibility of sub-clinical seminal vesicle involvement, this should be reflected in the definition of the CTV.

Comparative evaluation of image quality from three CT simulation scanners.

Today, radiation therapy (RT) is moving toward increased radiation dose to the tumor as a result of 3D conformal RT (3DCRT) and intensity-modulated RT (IMRT), which have been made possible by advances in volumetric-based image planning with digital imaging systems such as computed tomography (CT). Treatment planning for such RT requires superior CT image quality. Our goal in this study was to evaluate and to compare the image quality of three unique CT simulation scanners available at our center for both single- and multiple-slice helical scanners. These scanners included a conventional 70-cm bore single-slice scanner (Philips Medical Systems), a large 85-cm bore single-slice scanner (Philips Medical Systems), and a 70-cm bore multislice scanner (GE Medical Systems). Image quality was evaluated in terms of image noise, low-contrast detectability (LCD), limiting spatial resolution (modulation transfer function), and slice thickness accuracy in accordance with guidelines set out by the AAPM. A commercially available Catphan phantom was used to characterize image quality for both axial and helical modes of scanning. We found that image quality was generally comparable for all scanners. Limiting spatial resolution and slice thickness accuracy were comparable for all three scanners for both scanning modes. The multislice unit was superior in terms of noise content, resulting in improved visualization of small, low-contrast objects, which is of significant clinical importance, particularly for soft tissue delineation. In addition, the multislice unit optimizes volume coverage speed and longitudinal resolution without compromising image quality, a significant advantage for the radiation oncology environment.

A facility for magnetic resonance-guided radiation therapy.

Magnetic resonance (MR) imaging is routinely employed in the design of radiotherapy (RT) treatment plans for many disease sites. It is evident that tighter integration of MR imaging into the RT process would increase confidence in dose placement and facilitate the integration of new MR imaging information (including anatomical and functional imaging) into the therapy process. To this end, a dedicated MR-guided RT (MRgRT) facility has been created that integrates a state-of-the-art linear accelerator delivery system, high-dose rate brachytherapy afterloader, and superconducting MR scanner to allow MR-based online treatment guidance, adaptive replanning, and response monitoring while maintaining the clinical functionality of the existing delivery systems. This system is housed within a dedicated MRgRT suite and operates in a coordinated fashion to assure safe and efficient MRgRT treatments.

Automatic Segmentation of Lung Carcinoma Using 3D Texture Features in 18-FDG PET/CT.

Target definition is the largest source of geometric uncertainty in radiation therapy. This is partly due to a lack of contrast between tumor and healthy soft tissue for computed tomography (CT) and due to blurriness, lower spatial resolution, and lack of a truly quantitative unit for positron emission tomography (PET). First-, second-, and higher-order statistics, Tamura, and structural features were characterized for PET and CT images of lung carcinoma and organs of the thorax. A combined decision tree (DT) with K-nearest neighbours (KNN) classifiers as nodes containing combinations of 3 features were trained and used for segmentation of the gross tumor volume. This approach was validated for 31 patients from two separate institutions and scanners. The results were compared with thresholding approaches, the fuzzy clustering method, the 3-level fuzzy locally adaptive Bayesian algorithm, the multivalued level set algorithm, and a single KNN using Hounsfield units and standard uptake value. The results showed the DTKNN classifier had the highest sensitivity of 73.9%, second highest average Dice coefficient of 0.607, and a specificity of 99.2% for classifying voxels when using a probabilistic ground truth provided by simultaneous truth and performance level estimation using contours drawn by 3 trained physicians.