Coen R. N. Rasch

Definition of the prostate in CT and MRI: a multi-observer study

PURPOSE To determine, in three-dimensions, the difference between prostate delineation in magnetic resonance (MR) and computer tomography (CT) images for radiotherapy treatment planning. PATIENTS AND METHODS Three radiation oncologists, considered experts in the field, outlined the prostate without seminal vesicles both on CT, and axial, coronal, and sagittal MR images for 18 patients. To compare the resulting delineated prostates, the CT and MR scans were matched in three-dimensions using chamfer matching on bony structures. The volumes were measured and the interscan and interobserver variation was determined. The spatial difference between delineation in CT and MR (interscan variation) as well as the interobserver variation were quantified and mapped three-dimensionally (3D) using polar coordinates. A urethrogram was performed and the location of the tip of the dye column was compared with the apex delineated in CT and MR images. RESULTS Interscan variation: CT volumes were larger than the axial MR volumes in 52 of 54 delineations. The average ratio between the CT and MR volumes was 1.4 (standard error of mean, SE: 0.04) which was significantly different from 1 (p < 0.005). Only small differences were observed between the volumes outlined in the various MR scans, although the coronal MR volumes were smallest. The CT derived prostate was 8 mm (standard deviation, SD: 6 mm) larger at the base of the seminal vesicles and 6 mm (SD 4 mm) larger at the apex of the prostate than the axial MRI. Similar figures were obtained for the CT and the other MRI scans. Interobserver variation: The average ratio between the volume derived by one observer for a particular scan and patient and the average volume was 0.95, 0.97, and 1.08 (SE 0.01) for the three observers, respectively. The 3D pattern of the overall observer variation (1 SD) for CT and axial MRI was similar and equal to 3.5 to 2.8 mm at the base of the seminal vesicles and 3 mm at the apex. CONCLUSION CT-derived prostate volumes are larger than MR derived volumes, especially toward the seminal vesicles and the apex of the prostate. This interscan variation was found to be larger than the interobserver variation. Using MRI for delineation of the prostate reduces the amount of irradiated rectal wall, and could reduce rectal and urological complications.

Setup uncertainties of anatomical sub-regions in head-and-neck cancer patients after offline CBCT guidance

PURPOSE To quantify local geometrical uncertainties in anatomical sub-regions during radiotherapy for head-and-neck cancer patients. METHODS AND MATERIALS Local setup accuracy was analyzed for 38 patients, who had received intensity-modulated radiotherapy and were regularly scanned during treatment with cone beam computed tomography (CBCT) for offline patient setup correction. In addition to the clinically used large region of interest (ROI), we defined eight ROIs in the planning CT that contained rigid bony structures: the mandible, larynx, jugular notch, occiput bone, vertebrae C1-C3, C3-C5, and C5-C7, and the vertebrae caudal of C7. By local rigid registration to successive CBCT scans, the local setup accuracy of each ROI was determined and compared with the overall setup error assessed with the large ROI. Deformations were distinguished from rigid body movements by expressing movement relative to a reference ROI (vertebrae C1-C3). RESULTS The offline patient setup correction protocol using the large ROI resulted in residual systematic errors (1 SD) within 1.2 mm and random errors within 1.5 mm for each direction. Local setup errors were larger, ranging from 1.1 to 3.4 mm (systematic) and 1.3 to 2.5 mm (random). Systematic deformations ranged from 0.4 mm near the reference C1-C3 to 3.8 mm for the larynx. Random deformations ranged from 0.5 to 3.6 mm. CONCLUSION Head-and-neck cancer patients show considerable local setup variations, exceeding residual global patient setup uncertainty in an offline correction protocol. Current planning target volume margins may be inadequate to account for these uncertainties. We propose registration of multiple ROIs to drive correction protocols and adaptive radiotherapy to reduce the impact of local setup variations.

The European Society of Therapeutic Radiology and Oncology-European Institute of Radiotherapy (ESTRO-EIR) report on 3D CT-based in-room image guidance systems: a practical and technical review and guide.

The past decade has provided many technological advances in radiotherapy. The European Institute of Radiotherapy (EIR) was established by the European Society of Therapeutic Radiology and Oncology (ESTRO) to provide current consensus statement with evidence-based and pragmatic guidelines on topics of practical relevance for radiation oncology. This report focuses primarily on 3D CT-based in-room image guidance (3DCT-IGRT) systems. It will provide an overview and current standing of 3DCT-IGRT systems addressing the rationale, objectives, principles, applications, and process pathways, both clinical and technical for treatment delivery and quality assurance. These are reviewed for four categories of solutions; kV CT and kV CBCT (cone-beam CT) as well as MV CT and MV CBCT. It will also provide a framework and checklist to consider the capability and functionality of these systems as well as the resources needed for implementation. Two different but typical clinical cases (tonsillar and prostate cancer) using 3DCT-IGRT are illustrated with workflow processes via feedback questionnaires from several large clinical centres currently utilizing these systems. The feedback from these clinical centres demonstrates a wide variability based on local practices. This report whilst comprehensive is not exhaustive as this area of development remains a very active field for research and development. However, it should serve as a practical guide and framework for all professional groups within the field, focussed on clinicians, physicists and radiation therapy technologists interested in IGRT.

CD44 Expression Predicts Local Recurrence after Radiotherapy in Larynx Cancer

Purpose: To find molecular markers from expression profiling data to predict recurrence of laryngeal cancer after radiotherapy. Experimental Design: We generated gene expression data on pre-treatment biopsies from 52 larynx cancer patients. Patients developing a local recurrence were matched for T-stage, subsite, treatment, gender and age with non-recurrence patients. Candidate genes were then tested by immunohistochemistry on tumor material from a second series of 76 patients. Both series comprised early stage cancer treated with radiotherapy alone. Finally, gene expression data of eight larynx cancer cell lines with known radiosensitivity were analyzed. Results: Nineteen patients with a local recurrence were matched with 33 controls. Gene sets for hypoxia, proliferation and intrinsic radiosensitivity did not correlate with recurrence, whereas expression of the putative stem cell marker CD44 did. In a supervised analysis, probes for all three splice variants of CD44 on the array appeared in the top 10 most significantly correlated with local recurrence. Immunohistochemical analysis of CD44 expression on the independent validation series confirmed CD44s predictive potential. In 8 larynx cancer cell lines, CD44 gene expression did not correlate with intrinsic radiosensitivity although it did correlate significantly with plating efficiency, consistent with a relationship with stem cell content. Conclusions: CD44 was the only biological factor tested which significantly correlated with response to radiotherapy in early stage larynx cancer patients, both at the mRNA and protein levels. Further studies are needed to confirm this and to assess how general these findings are for other head and neck tumor stages and sites. Clin Cancer Res; 16(21); 5329–38. ©2010 AACR.

Three-dimensional analysis of delineation errors, setup errors, and organ motion during radiotherapy of bladder cancer

PURPOSE To quantify in three dimensions the geometric uncertainties of bladder irradiation (i.e., uncertainties in target delineation, organ motion, and patient setup). METHODS AND MATERIALS Pelvic CT images were obtained for 10 male bladder cancer patients. Apart from the initial planning CT scan, three follow-up scans were made for each of the patients. The bladder volumes in the planning CT scan were outlined by seven radiation oncologists. One observer also delineated the bladder volumes in the follow-up scans. Two-dimensional scalar maps of the interobserver variation and organ motion of the bladder surfaces were constructed. The setup errors were derived from the portal imaging results of the pooled group of bladder and prostate patients. RESULTS All bladder volumes were consistently outlined by all observers. Generally small variations occurred (1.5-3 mm, 1 SD), although in 50% of the patients, larger discrepancies were observed in discriminating the bladder from the base of the prostate. Analysis of the portal imaging data showed setup errors of up to 3 mm (1 SD). Organ motion is the predominant geometric uncertainty in the radiotherapy process (5 mm, 1 SD, at the cranial side of the bladder), although 9 of 10 patients were able to preserve a fairly reproducible bladder volume during the complete treatment course. CONCLUSION Anisotropic margins between the clinical target volume and planning target volume are needed in conformal radiotherapy of the bladder. Especially at the cranial side of the bladder, larger margins are needed because of the impact of bladder shape variation.

How should we measure and report radiotherapy-induced xerostomia?

Xerostomia is commonly measured and graded using objective measures of major salivary gland output and observer-rated toxicity grading. The separation between the different grades is somewhat ambiguous in the current toxicity grading systems. We propose a new grading system based primarily on the functional deficits associated with xerostomia. Salivary flow rates have been added as a criterion to the grading system, notwithstanding the weak correlation reported in most studies between the symptoms and objective functional measures. In addition to the observer-rated toxicity grading, recording of patient-reported quality of life, using validated instruments, is encouraged.

A general methodology for three-dimensional analysis of variation in target volume delineation.

A generic method for three-dimensional (3-D) evaluation of target volume delineation in multiple imaging modalities is presented. The evaluation includes geometrical and statistical methods to estimate observer differences and variability in defining the Gross Tumor Volume (GTV) in relation to the diagnostic CT and MRI modalities. The geometrical method is based on mapping the 3-D shape of the target volume to a scalar representation, thus enabling a one-dimensional statistical analysis. The statistical method distinguishes observer and modality related uncertainties, which are expressed in terms of three error components: random observer deviations, systematic observer differences, and systematic modality differences. Monte Carlo simulations demonstrate that the standard errors of each of the three model parameters are inversely proportional to the square root of the product of the patient group size and the number of observers and proportional to the intraobserver variation. For 18 patients and 3 observers the standard errors of the estimated systematic modality and observer differences are 19% and 14% of the intraobserver standard deviation, respectively. A scalar representation of the shape of the prostate, delineated by 3 observers for 18 patients, was obtained by sampling the distance between the average center of gravity of the prostate in CT and the prostate surface for a large number of directions (2500), using polar coordinates. Observer variability and differences were obtained by applying the statistical method to the samples independently. The intraobserver variation for CT was largest in regions near the seminal vesicles (s.d: 3 mm) and the apex (s.d: 3 mm). The systematic observer variation in CT was largest in a region near the plexus Santorini, at the caudal-anterior side of the prostate (s.d.: 2 mm). The sensitivity for the choice of origin was tested by using the average center of gravity from axial MRI instead of CT. The results were almost identical. The polar map measures distances in the scanning directions. A correction procedure to get the variability in directions perpendicular to the surface of the prostate yielded variations that were a factor of 0.85 smaller for all directions. It is concluded that by separating the shape evaluation in a geometrical and a statistical part, the complexity of the analysis of 3-D shape differences can be significantly reduced. The method was successfully applied to a group of prostate patients, where we demonstrated that delineation variability is nonhomogeneous, with the largest variations occurring near the seminal vesicles and the apex.

Reduction of dose delivered to the rectum and bulb of the penis using MRI delineation for radiotherapy of the prostate

PURPOSE The prostate volume delineated on MRI is smaller than on CT. The purpose of this study was to determine the influence of MRI- vs. CT-based prostate delineation using multiple observers on the dose to the target and organs at risk during external beam radiotherapy. MATERIALS AND METHODS CT and MRI scans of the pelvic region were made of 18 patients and matched three-dimensionally on the bony anatomy. Three observers delineated the prostate using both modalities. A fourth observer delineated the rectal wall and the bulb of the penis. The planning treatment volume (PTV) was generated from the delineated prostates with a margin of 10 mm in three-dimensions. A three-field treatment plan with a prescribed dose of 78 Gy to the International Commission on Radiation Units and Measurements point was automatically generated from each PTV. Dose-volume histograms were calculated of all PTVs, rectal walls, and penile bulbs. The equivalent uniform dose was calculated for the rectal wall using a volume exponent (n = 0.12). RESULTS The equivalent uniform dose of the CT rectal wall in plans based on the CT-delineated prostate was, on average, 5.1 Gy (SEM 0.5) greater than in the plans based on the MRI-delineated prostate. For the MRI rectal wall, this difference was 3.6 Gy (SEM 0.4). Allowing for the same equivalent uniform dose to the CT rectal wall, the prescribed dose to the PTV could be raised from 78 to 85 Gy when using the MRI-delineated prostate for treatment planning. The mean dose to the bulb of the penis was 11.6 Gy (SEM 1.8) lower for plans based on the MRI-delineated prostate. The mean coverage (volume of the PTV receiving > or =95% of the prescribed dose) was 99.9% for both modalities. The interobserver coverage (coverage of the PTV by a treatment plan designed for the PTV delineated by another observer in the same modality) was 97% for both modalities. The MRI rectum was significantly more ventrally localized than the CT rectum, probably because of the rounded tabletop and no knee support on the MRI scanner. CONCLUSIONS The dose delivered to the rectal wall and bulb of the penis is significantly reduced with treatment plans based on the MRI-delineated prostate compared with the CT-delineated prostate, allowing a dose escalation of 2.0-7.0 Gy for the same rectal wall dose. The interobserver coverage was the same for CT and MRI delineation of the prostate. A statistically significant difference in position between the CT- and MRI-delineated rectum was observed, probably owing to a different tabletop and use of knee support.

Breast Patient Setup Error Assessment: Comparison of Electronic Portal Image Devices and Cone-Beam Computed Tomography Matching Results

PURPOSE To quantify the differences in setup errors measured with the cone-beam computed tomography (CBCT) and electronic portal image devices (EPID) in breast cancer patients. METHODS AND MATERIALS Repeat CBCT scan were acquired for routine offline setup verification in 20 breast cancer patients. During the CBCT imaging fractions, EPID images of the treatment beams were recorded. Registrations of the bony anatomy for CBCT to planning CT and EPID to digitally reconstructed-radiographs (DRRs) were compared. In addition, similar measurements of an anthropomorphic thorax phantom were acquired. Bland-Altman and linear regression analysis were performed for clinical and phantom registrations. Systematic and random setup errors were quantified for CBCT and EPID-driven correction protocols in the EPID coordinate system (U, V), with V parallel to the cranial-caudal axis and U perpendicular to V and the central beam axis. RESULTS Bland-Altman analysis of clinical EPID and CBCT registrations yielded 4 to 6-mm limits of agreement, indicating that both methods were not compatible. The EPID-based setup errors were smaller than the CBCT-based setup errors. Phantom measurements showed that CBCT accurately measures setup error whereas EPID underestimates setup errors in the cranial-caudal direction. In the clinical measurements, the residual bony anatomy setup errors after offline CBCT-based corrections were Σ(U) = 1.4 mm, Σ(V) = 1.7 mm, and σ(U) = 2.6 mm, σ(V) = 3.1 mm. Residual setup errors of EPID driven corrections corrected for underestimation were estimated at Σ(U) = 2.2mm, Σ(V) = 3.3 mm, and σ(U) = 2.9 mm, σ(V) = 2.9 mm. CONCLUSION EPID registration underestimated the actual bony anatomy setup error in breast cancer patients by 20% to 50%. Using CBCT decreased setup uncertainties significantly.

Intra-arterial versus intravenous chemoradiation for advanced head and neck cancer: Results of a randomized phase 3 trial

Chemoradiation is the preferred treatment for advanced stage IV head and neck cancer. Higher doses of chemotherapy yielded promising results in vitro and vivo, confirmed by intra‐arterial (IA) cisplatin‐based chemoradiation in phase 2 studies.