99mTc Hynic-rh-Annexin V scintigraphy for in vivo imaging of apoptosis in patients with head and neck cancer treated with chemoradiotherapy

PURPOSE: The purpose of this study was to determine the value of (99m)Tc Hynic-rh-Annexin-V-Scintigraphy (TAVS), a non-invasive in vivo technique to demonstrate apoptosis in patients with head and neck squamous cell carcinoma. METHODS: TAVS were performed before and within 48 h after the first course of cisplatin-based chemoradiation. Radiation dose given to the tumour at the time of post-treatment TAVS was 6-8 Gy. Single-photon emission tomography data were co-registered to planning CT scan. Complete sets of these data were available for 13 patients. The radiation dose at post-treatment TAVS was calculated for several regions of interest (ROI): primary tumour, involved lymph nodes and salivary glands. Annexin uptake was determined in each ROI, and the difference between post-treatment and baseline TAVS represented the absolute Annexin uptake: Delta uptake (DeltaU). RESULTS: In 24 of 26 parotid glands, treatment-induced Annexin uptake was observed. Mean DeltaU was significantly correlated with the mean radiation dose given to the parotid glands (r = 0.59, p = 0.002): Glands that received higher doses showed more Annexin uptake. DeltaU in primary tumour and pathological lymph nodes showed large inter-patient differences. A high correlation was observed on an inter-patient level (r = 0.71, p = 0.006) between the maximum DeltaU in primary tumour and in the lymph nodes. CONCLUSIONS: Within the dose range of 0-8 Gy, Annexin-V-scintigraphy showed a radiation-dose-dependent uptake in parotid glands, indicative of early apoptosis during treatment. The inter-individual spread in Annexin uptake in primary tumours could not be related to differences in dose or tumour volume, but the Annexin uptake in tumour and lymph nodes were closely correlated. This effect might represent a tumour-specific apoptotic respons

Application of video imaging for improvement of patient set-up.

BACKGROUND AND PURPOSE: For radiotherapy of prostate cancer, the patient is usually positioned in the left-right (LR) direction by aligning a single marker on the skin with the projection of a room laser. The aim of this study is to investigate the feasibility of a room-mounted video camera in combination with previously acquired CT data to improve patient set-up along the LR axis. MATERIAL AND METHODS: The camera was mounted in the treatment room at the caudal side of the patient. For 22 patients with prostate cancer 127 video and portal images were acquired. The set-up error determined by video imaging was found by matching video images with rendered CT images using various techniques. This set-up error was retrospectively compared with the set-up error derived from portal images. It was investigated whether the number of corrections based on portal imaging would decrease if the information obtained from the video images had been used prior to irradiation. Movement of the skin with respect to bone was quantified using an analysis of variance method. RESULTS: The measurement of the set-up error was most accurate for a technique where outlines and groins on the left and right side of the patient were delineated and aligned individually to the corresponding features extracted from the rendered CT image. The standard deviations (SD) of the systematic and random components of the set-up errors derived from the portal images in the LR direction were 1.5 and 2.1 mm, respectively. When the set-up of the patients was retrospectively adjusted based on the video images, the SD of the systematic and random errors decreased to 1.1 and 1.3 mm, respectively. From retrospective analysis, a reduction of the number of set-up corrections (from nine to six corrections) is expected when the set-up would have been adjusted using the video images. The SD of the magnitude of motion of the skin of the patient with respect to the bony anatomy was estimated to be 1.1 mm. CONCLUSION: Video imaging is an accurate technique for measuring the set-up of prostate cancer patients in the LR direction. The outline of the patient is a more accurate estimate of the set-up of the bony anatomy than the marker on the patient's abdome

Prognostic value of primary tumor volume after concurrent chemoradiation with daily low-dose cisplatin for advanced-stage head and neck carcinoma

BACKGROUND: The purpose of this study was to evaluate the prognostic value of tumor volume in head and neck squamous cell carcinoma treated with chemoradiation. METHODS: Forty-six patients were treated with radiotherapy and cisplatin (6 mg/m(2) IV x 20, daily). Baseline primary tumor volume was recorded from MRI scans. The prognostic impact of tumor volume and other factors for locoregional control, disease-free survival (DFS), and overall survival (OS) was tested. RESULTS: Mean tumor volume was 28 cm(3) (median 23 cm(3); range, 3-112). The locoregional control rate at 3 years was 81% for patients with tumor volumes or = median (p = .036). At multivariate analysis, it appeared that tumor volume remained an independent determinant of locoregional control and survival when adjusted for other factors. CONCLUSIONS: In advanced-stage head and neck squamous cell carcinoma treated with concurrent chemoradiation, primary tumor volume is associated with locoregional control and survival. Larger studies are needed to confirm whether incorporation of tumor volume in the staging system improves prediction of treatment outcome and can serve as a tool to guide treatment option

Residual seminal vesicle displacement in marker-based image-guided radiotherapy for prostate cancer and the impact on margin design.

The objectives of this study were to quantify residual interfraction displacement of seminal vesicles (SV) and investigate the efficacy of rotation correction on SV displacement in marker-based prostate image-guided radiotherapy (IGRT). We also determined the effect of marker registration on the measured SV displacement and its impact on margin design. SV displacement was determined relative to marker registration by using 296 cone beam computed tomography scans of 13 prostate cancer patients with implanted markers. SV were individually registered in the transverse plane, based on gray-value information. The target registration error (TRE) for the SV due to marker registration inaccuracies was estimated. Correlations between prostate gland rotations and SV displacement and between individual SV displacements were determined. The SV registration success rate was 99%. Displacement amounts of both SVs were comparable. Systematic and random residual SV displacements were 1.6 mm and 2.0 mm in the left-right direction, respectively, and 2.8 mm and 3.1 mm in the anteroposterior (AP) direction, respectively. Rotation correction did not reduce residual SV displacement. Prostate gland rotation around the left-right axis correlated with SV AP displacement (R(2) = 42%); a correlation existed between both SVs for AP displacement (R(2) = 62%); considerable correlation existed between random errors of SV displacement and TRE (R(2) = 34%). Considerable residual SV displacement exists in marker-based IGRT. Rotation correction barely reduced SV displacement, rather, a larger SV displacement was shown relative to the prostate gland that was not captured by the marker position. Marker registration error partly explains SV displacement when correcting for rotations. Correcting for rotations, therefore, is not advisable when SV are part of the target volume. Margin design for SVs should take these uncertainties into accoun

A model to predict bladder shapes from changes in bladder and rectal filling.

The purpose of this study is to develop a model that quantifies in three dimensions changes in bladder shape due to changes in bladder and/or rectal volume. The new technique enables us to predict changes in bladder shape over a short period of time, based on known urinary inflow. Shortly prior to the treatment, the patient will be scanned using a cone beam CT scanner (x-ray volume imager) that is integrated with the linear accelerator. After (automated) delineation of the bladder, the model will be used to predict the short-term shape changes of the bladder for the time interval between image acquisition and dose delivery. The model was developed using multiple daily CT scans of the pelvic area of 19 patients. For each patient, the rigid bony structure in follow-up scans was matched to that of the planning CT scan, and the outer bladder and rectal wall were delineated. Each bladder wall was subdivided in 2500 domains. A fixed reference point inside the bladder was used to calculate for each bladder structure a "Mercator-like" 2D scalar map (similar to a height map of the globe), containing the distances from this reference point to each domain on the bladder wall. Subsequently, for all bladder shapes of a patient and for all domains on the wall individually, the distance to the reference point was fitted by a linear function of both bladder and rectal volume. The model uses an existing bladder structure to create a new structure via expansion (or contraction), until the expressed volume is reached. To evaluate the predictive power of the model, the jack-knife method was used. The errors in the fitting procedure depended on the part of the bladder and range from 0 to 0.5 cm (0.2 cm on average). It was found that a volume increase of 150 cc can lead to a displacement up to about 2.5 cm of the cranial part of the bladder. With the model, the uncertainty in the position of the bladder wall can be reduced down to a maximum value of about 0.5 cm in case the bladder volume increase is known. Furthermore, it was found that a change in rectal filling causes a shift of the bladder, while its shape is hardly influenced. In conclusion, we developed a model that describes the bladder shape and position as a function of the bladder volume and the rectal filling. The model accurately describes the complex shape of the bladder as it works on each domain of the bladder separatel

Automatic prostate localization on cone-beam CT scans for high precision image-guided radiotherapy.

PURPOSE: Previously, we developed an automatic three-dimensional gray-value registration (GR) method for fast prostate localization that could be used during online or offline image-guided radiotherapy. The method was tested on conventional computed tomography (CT) scans. In this study, the performance of the algorithm to localize the prostate on cone-beam CT (CBCT) scans acquired on the treatment machine was evaluated. METHODS AND MATERIALS: Five to 17 CBCT scans of 32 prostate cancer patients (332 scans in total) were used. For 18 patients (190 CBCT scans), the CBCT scans were acquired with a collimated field of view (FOV) (craniocaudal). This procedure improved the image quality considerably. The prostate (i.e., prostate plus seminal vesicles) in each CBCT scan was registered to the prostate in the planning CT scan by automatic 3D gray-value registration (normal GR) starting from a registration on the bony anatomy. When these failed, registrations were repeated with a fixed rotation point locked at the prostate apex (fixed apex GR). Registrations were visually assessed in 3D by one observer with the help of an expansion (by 3.6 mm) of the delineated prostate contours of the planning CT scan. The percentage of successfully registered cases was determined from the combined normal and fixed apex GR assessment results. The error in gray-value registration for both registration methods was determined from the position of one clearly defined calcification in the prostate gland (9 patients, 71 successful registrations). Results: The percentage of successfully registered CBCT scans that were acquired with a collimated FOV was about 10% higher than for CBCT scans that were acquired with an uncollimated FOV. For CBCT scans that were acquired with a collimated FOV, the percentage of successfully registered cases improved from 65%, when only normal GR was applied, to 83% when the results of normal and fixed apex GR were combined. Gray-value registration mainly failed (or registrations were difficult to assess) because of streaks in the CBCT scans caused by moving gas pockets in the rectum during CBCT image acquisition (i.e., intrafraction motion). The error in gray-value registration along the left-right, craniocaudal, and anteroposterior axes was 1.0, 2.4, and 2.3 mm (1 SD) for normal GR, and 1.0, 2.0, and 1.7 mm (1 SD) for fixed apex GR. The systematic and random components of these SDs contributed approximately equally to these SDs, for both registration methods. Conclusions: The feasibility of automatic prostate localization on CBCT scans acquired on the treatment machine using an adaptation of the previously developed three-dimensional gray-value registration algorithm, has been validated in this study. Collimating the FOV during CBCT image acquisition improved the CBCT image quality considerably. Artifacts in the CBCT images caused by large moving gas pockets during CBCT image acquisition were the main cause for unsuccessful registration. From this study, we can conclude that CBCT scans are suitable for online and offline position verification of the prostate, as long as the amount of nonstationary gas is limite

Quantification of shape variation of prostate and seminal vesicles during external beam radiotherapy.

PURPOSE: The prostate is known to translate and rotate under influence of rectal filling changes and many studies have addressed the magnitude of these motions. However, prostate shape variations also have been reported. For image-guided radiotherapy, it is essential to know the relative magnitude of translations, rotations, and shape variation so that the most appropriate correction strategy can be chosen. However, no quantitative analysis of shape variation has been performed. It is, therefore, the purpose of this article to develop a method to determine shape variation of complex organs and apply it to determine shape variation during external beam radiotherapy of a GTV (gross tumor volume) consisting of prostate and seminal vesicles. METHODS AND MATERIALS: For this study, the data of 19 patients with prostate cancer were used. Each patient received a planning computed tomography (CT) scan and 8-12 (11 on average) repeat CT scans that were made during the course of conformal radiotherapy. One observer delineated the GTV in all scans, and volume variations were measured. After matching the GTVs for each patient for translation and rotation, a coverage probability matrix was constructed and the 50% isosurface was taken to determine the average GTV surface. Perpendicular distances between the average GTV and the individual GTVs were calculated for each point of the average GTV, and their variation was expressed in terms of local standard deviation (SD). The local SDs of the shape variation of all 19 patients were mapped onto a reference case by matching and morphing of the individual average GTVs. Repeated delineation of the GTV was done for 6 patients to determine intraobserver variation. Finally, the measured shape variation was corrected for intraobserver variation to estimate the "real" shape variation. RESULTS: No significant variations in GTV volume were observed. The measured shape variation (including delineation variation) was largest at the tip of the vesicles (SD = 2.0 mm), smallest at the left and right side of the prostate (SD = 1.0 mm), and average elsewhere (SD = 1.5 mm). At the left, right, and cranial sides of the prostate, the intraobserver variation was of the same order of magnitude as the measured shape variation; elsewhere it was smaller. However, the accuracy of the estimated SD for intraobserver variation was about half of the accuracy of the estimated SD for the measured shape variation, giving an overall uncertainty of maximum 0.6 mm SD in the estimate of the "real" shape variation. The "real" shape variation was small at the left, right, and cranial side of the prostate (SD <0.5 mm) and between 0.5 mm and 1.6 mm elsewhere. CONCLUSIONS: We developed a method to quantify shape variation of organs with a complex shape and applied it to a GTV consisting of prostate and seminal vesicles. Deformation of prostate and seminal vesicles during the course of radiotherapy is small (relative to organ motion). Therefore, it is a valid approximation in image-guided radiotherapy of prostate cancer, in first order, to correct only for setup errors and organ motion. Prostate and seminal vesicles deformation can be considered as a second-order effec