T. Schakel

Diffusion weighted MRI in head-and-neck cancer: geometrical accuracy.

INTRODUCTION The aim of this study is to assess the geometric accuracy of diffusion weighted (DW)-MRI by quantification of geometric distortions in the gross tumor volume (GTV) in head and neck (HN) cancer. MATERIALS & METHODS A retrospective analysis was performed on the data of 23 patients (with 24 lesions). For these patients, magnetic field maps and DW-MRI were acquired. The magnetic field maps were converted to voxel displacement maps. GTV delineations were transferred onto these voxel displacement maps and the voxel shifts in the GTV were analyzed. RESULTS The median shift was 3.2mm and the maximal posterior and anterior shifts were up to 15.0 and 26.0mm respectively. The range of shifts varied from 11.8 to 25.6mm. The percentage of GTV voxels that showed a shift of at least 6mm was found to be 23.2%. CONCLUSIONS Current DW-MRI images of HN tumors show severe distortions up to centimeters, which restrict the use of DW-MRI scans for GTV definition in RT treatment planning.

MRI to quantify early radiation-induced changes in the salivary glands.

PURPOSE We investigated radiation-induced changes in the salivary glands, 6 weeks after RT, using MRI. MATERIALS AND METHODS Eighteen oropharyngeal cancer patients were treated with salivary gland sparing IMRT. All patients received a 3T MRI exam before and 6 weeks after the end of RT, including a T(1)-weighted (T(1)w), a T(2)-weighted (T(2)w), and a dynamic contrast-enhanced (DCE) MRI. For both time points separately, the parotid and submandibular glands were delineated on the MR images. Differences in median signal intensity and signal variation within the glands were tested for significance. Correlations were studied between the MR changes and the planned RT dose. RESULTS The volume of the glands reduced significantly by 25%. The T(1)w signal decreased by 10% and the T(2)w signal increased by 23%. The k(ep) value decreased, while the v(e) increased. A correlation of the changes in T(2)w signal with the mean dose was found in both glands. CONCLUSIONS Overall radiation-induced changes and volume loss were observed in the parotid and submandibular gland using MR. The observed differences indicated an increased water content such as found in oedema. The overall changes could be related to the mean dose, with a slightly greater impact in the high dose area.

Modality-specific target definition for laryngeal and hypopharyngeal cancer on FDG-PET, CT and MRI

BACKGROUND AND PURPOSE The goal of this study was to improve target definition by deriving modality-specific margins for clinical target volumes (CTV) for laryngeal and hypopharyngeal cancer on CT, MRI and 18-FDG-PET. MATERIAL AND METHODS Twenty-five patients with T3/T4 laryngeal/hypopharyngeal cancer underwent CT, MRI and 18-FDG-PET scans before laryngectomy. HE-sections were obtained from the surgical specimen and tumor was delineated (tumorHE). The GTVs on CT and MRI were delineated in consensus. PET-based GTVs were automatically segmented. The three-dimensionally reconstructed specimen was registered to the various images. Modality-specific CTV margins were derived and added to the GTVs to achieve adequate tumor coverage. The resulting CTVs were compared with each other, to tumorHE, and to CTVCT10 constructed on CT with the clinical margin of 10mm. RESULTS CTV margins of 4.3mm (CT), 6.1mm (MRI) and 5.2mm (PET) were needed to achieve adequate tumor coverage. The median volumes of the resulting modality-specific CTVs were 44ml (CT), 48ml (MRI) and 39ml (PET), while the CTV10mm was 80ml. CONCLUSION For laryngohypopharyngeal tumors, 45-52% target volume reduction compared with CTV10mm is achievable when modality-specific CTV margins are used. PET-based CTVs were significantly smaller compared to CT- and MRI-based CTVs.

The accuracy of target delineation in laryngeal and hypopharyngeal cancer

Abstract Background and purpose. To determine the spatial correspondence between the gross tumor volume (GTV) delineated on computer tomography (CT) and the actual tumor on histopathology. Material and methods. Sixteen patients with T3 or T4 laryngeal or hypopharyngeal cancer underwent a CT scan before total laryngectomy. The GTV was delineated on CT by three independent observers and by consensus between the three observers. After surgery, whole-mount hematoxylin-eosin stained (H&E) sections were obtained. One pathologist delineated the tumor in the H&E sections (tumorH&E). The reconstructed specimen was registered to the CT scan in order to compare the GTV to the tumorH&E in three dimensions. The overlap between the GTV and the tumorH&E was calculated and the distance between the volumes was determined. Results. Tumor tissue was delineated in 203 of 516 H&E sections. For 14 patients a detailed analysis could be performed. The GTV volume was on average 1.7 times larger than the volume of the tumorH&E. The mean coverage of the tumorH&E by the consensus GTV was 88%. tumorH&E tissue was found at 1.6 mm to 12.9 mm distance outside the GTV depending on observer and patient. Conclusions. GTVs delineated on CT for laryngeal and hypopharyngeal cancer were 1.7 times larger than the tumor. Complete coverage of the tumor by the GTV was, however, not obtained.

Inter-observer agreement of MRI-based tumor delineation for preoperative radiotherapy boost in locally advanced rectal cancer

BACKGROUND While surgery remains the cornerstone of rectal cancer treatment, organ-preservation is upcoming. Therefore, neo-adjuvant treatment should be optimized. By escalating doses, response can be increased. To limit toxicity of boost, accurate gross tumor volume (GTV) definition is required. MRI, especially undeformed fast spin echo diffusion-weighted MRI (DWI), looks promising for delineation. However, inconsistencies between observers should be quantified before clinical implementation. We aim to find which MRI sequence (T2w, DWI or combination) is optimal and clinically useful for GTV definition by evaluating inter-observer agreement. METHODS Locally advanced rectal cancer patients (tumors <10 cm from anal verge) were scanned on 3T MRI transverse T2w and DWI (b=800 s/mm(2)). Three independent observers delineated T2w, DWI and combination (Combi) after training-set. Volumes, conformity index (CI), and maximum Hausdorff distance (HD) were calculated between any observer-pair per patient per modality. RESULTS Twenty-four consecutive patients were included. One patient had cT2 (4.2%), 19 cT3 (79.1%) and 4 cT4 (16.7%), with 2 clinical node negative (8.3%), 4 cN1 (16.7%), and 18 cN2 (75.0%) on MRI. From 24 patients, 70 sequences were available (24x T2, 23x DWI, and 23x Combi). Between observers, no significant volume differences were observed per modality. T2 showed significantly largest volumes compared to DWI (mean difference 19.85 ml, SD 17.42, p<0.0001) and Combi (mean difference 7.16 ml, SD 11.58, p<0.0001). Mean CI was 0.70, 0.71 and 0.69 for T2, DWI and Combi respectively (p>0.61). Average HD was largest on T2 (18.60mm, max 31.40 mm, min 9.20mm). DISCUSSION Delineation on DWI resulted in delineation of the smallest volumes with similar consistency and mean distances, but with slightly lower Hausdorff distances compared to T2 and Combi. However, with lack of a gold standard it remains difficult to establish if delineations also represent true tumor. Study strengths were DWI adaptation to exclude geometrical distortions and training-set. DWI shows great potential for delineation purposes as long as sufficient experience exists and geometrical distortions are eliminated.

Validated guidelines for tumor delineation on magnetic resonance imaging for laryngeal and hypopharyngeal cancer

Abstract Background: Validation of magnetic resonance imaging (MRI) and development of guidelines for the delineation of the gross tumor volume (GTV) is of utmost importance to benefit from the visibility of anatomical details on MR images and to achieve an accurate GTV delineation. In the ideal situation, the GTV delineation corresponds to the histopathologically determined ‘true tumor volume’. Consequently, we developed guidelines for GTV delineation of laryngeal and hypopharyngeal tumors on MRI and determined the accuracy of the resulting delineation of the tumor outline on histopathology as gold standard. Material and methods: Twenty-seven patients with T3 or T4 laryngeal/hypopharyngeal cancer underwent a MRI scan before laryngectomy. Hematoxylin and eosin sections were obtained from surgical specimens and tumor was delineated by one pathologist. GTV was delineated on MR images by three independent observers in two sessions. The first session (del1) was performed according to clinical practice. In the second session (del2) guidelines were used. The reconstructed specimen was registered to the MR images for comparison of the delineated GTVs to the tumor on histopathology. Volumes and overlap parameters were analyzed. A target margin needed to assure tumor coverage was determined. Results: The median GTVs (del1: 19.4 cm3, del2: 15.8 cm3) were larger than the tumor volume on pathology (10.5 cm3). Comparable target margins were needed for both delineation sessions to assure tumor coverage. By adding these margins to the GTVs, the target volumes for del1 (median: 81.3 cm3) were significantly larger than for del2 (median: 64.2 cm3) (p ≤ 0.0001) with similar tumor coverage. Conclusions: In clinical radiotherapy practice, the delineated GTV on MRI is twice as large as the tumor volume. Validated delineation guidelines lead to a significant decrease in the overestimation of the tumor volume.

Diffusion weighted MRI with minimal distortion in head-and-neck radiotherapy using a turbo spin echo acquisition method

Purpose: Diffusion‐weighted (DW) MRI, showing high contrast between tumor and background tissue, is a promising technique in radiotherapy for tumor delineation. However, its use for head‐and‐neck patients is hampered by poor geometric accuracy in conventional echo planar imaging (EPI) DW‐MRI. An alternative turbo spin echo sequence, DW‐SPLICE, is implemented and demonstrated in patients. Methods: The DW‐SPLICE sequence was implemented on a 3.0 T system and evaluated in 10 patients. The patients were scanned in treatment position, using a customized head support and immobilization mask. Image distortions were quantified at the gross tumor volume (GTV) using field map analysis. The apparent diffusion coefficient (ADC) was evaluated using an ice water phantom. Results: The DW images acquired by DW‐SPLICE showed no image distortions. Field map analysis at the gross tumor volumes resulted in a median distortion of 0.2 mm for DW‐SPLICE, whereas for the conventional method this was 7.2 mm. ADC values, measured using an ice water phantom were in accordance with literature values. Conclusions: The implementation of DW‐SPLICE allows for diffusion‐weighted imaging of patients in treatment position with excellent geometrical accuracy. The images can be used to facilitate target volume delineation in RT treatment planning.

Interobserver variation among pathologists for delineation of tumor on H&E-sections of laryngeal and hypopharyngeal carcinoma. How good is the gold standard?

in tumor delineation studies for radiotherapy, histopathology is used for validation purposes [1–7]. Validation of tumor delineation is a complex procedure and relatively few studies have been performed in the research field of head-and-neck cancer [3,5,8]. in these studies, whole mount sections of laryngectomy specimens were obtained. The tumor was delineated by a pathologist and used to validate various imaging modalities, e.g. computed tomography (CT), magnetic resonance imaging (MRi), and positron emission tomography (PET) for their ability to distinguish tumor tissue. For the interpretation of validation studies, the variation of tumor outline on histopathology is crucial, as it is used as gold standard for tumor delineation in clinical imaging studies as currently performed by our institute [3,5,9]. However, a study on the reproducibility of tumor outline is missing. The aim of this study is to determine the variation of tumor delineation among pathologists on H&E-sections for laryngeal and hypopharyngeal carcinoma to quantify the uncertainties in the gold standard in the context of imaging validation studies for laryngeal and hypopharyngeal carcinoma.

Evaluation of diffusion weighted imaging for tumor delineation in head-and-neck radiotherapy by comparison with automatically segmented 18F-fluorodeoxyglucose positron emission tomography

Background and purpose Diffusion weighted (DW) MRI may facilitate target volume delineation for head-and-neck (HN) radiation treatment planning. In this study we assessed the use of a dedicated, geometrically accurate, DW-MRI sequence for target volume delineation. The delineations were compared with semi-automatic segmentations on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) images and evaluated for interobserver variation. Methods and materials Fifteen HN cancer patients underwent both DW-MRI and FDG-PET for RT treatment planning. Target delineation on DW-MRI was performed by three observers, while for PET a semi-automatic segmentation was performed using a Gaussian mixture model. For interobserver variation and intermodality variation, volumes, overlap metrics and Hausdorff distances were calculated from the delineations. Results The median volumes delineated by the three observers on DW-MRI were 10.8, 10.5 and 9.0 cm3 respectively, and was larger than the median PET volume (8.0 cm3). The median conformity index of DW-MRI for interobserver variation was 0.73 (range 0.38–0.80). Compared to PET, the delineations on DW-MRI by the three observers showed a median dice similarity coefficient of 0.71, 0.69 and 0.72 respectively. The mean Hausdorff distance was small with median (range) distances between PET and DW-MRI of 2.3 (1.5–6.8), 2.5 (1.6–6.9) and 2.0 (1.35–7.6) mm respectively. Over all patients, the median 95th percentile distances were 6.0 (3.0–13.4), 6.6 (4.0–24.0) and 5.3 (3.4–26.0) mm. Conclusion Using a dedicated DW-MRI sequence, target volumes could be defined with good interobserver agreement and a good overlap with PET. Target volume delineation using DW-MRI is promising in head-and-neck radiotherapy, combined with other modalities, it can lead to more precise target volume delineation.

Target Volume Delineation Using Diffusion-weighted Imaging for MR-guided Radiotherapy: A Case Series of Laryngeal Cancer Validated by Pathology

In radiotherapy treatment planning, tumor delineation based on diffusion-weighted imaging (DWI) by magnetic resonance imaging (MRI) is a promising technique. MR-only-based target definition becomes important with the recent development of MRI integrated radiotherapy treatment modalities. In this case series, DWI-based gross tumor volume (GTV) was validated using pathology and compared with a clinical GTV based on computed tomography (CT) imaging and MRI. This case series includes three patients with a laryngeal tumor. Prior to total laryngectomy (TLE), imaging was performed on CT and MRI, including a DWI scan. After TLE, the surgical specimen was processed and cut into 3-mm thick slices. The tumor was delineated on hematoxylin-eosin (HE) stained sections by a pathologist (tumorHE). This pathological imaging, including the tumorHE delineation, was three-dimensionally reconstructed and registered to the imaging. The GTV was delineated by a radiation oncologist based on CT and MR imaging (GTVclinical) and semi-automatically delineated based on DWI (GTVDWI). The microscopic tumor extent outside the GTVDWI contour was 3.0 mm, 2.7 mm, and 11.3 mm for cases I, II, and III, respectively. The microscopic tumor extent outside the GTVclinical was 7.5 mm, 2.1 mm, and 1.5 mm for cases I, II, and III, respectively. The tumor, on histology, was covered by the GTVs for 80%, 74%, and 31% (GTVDWI) and 73%, 72%, and 89% (GTVclinical) for the three subsequent cases, respectively. The GTVDWI resembled the tumorHE more than the GTVclinical in case I and case II. In case III, GTVDWI missed the caudal part of the tumor that was included in the clinical delineation due to a lack of contrast and the heterogeneous signal intensity of the tumor in DWI. In this case series, we showed the potential of DWI for MR-guided radiotherapy treatment if a clear contrast is visible. DWI-based GTV delineation might be a fast alternative to manual delineation, which could speed up the on-table target definition using an MRI-linac system. A larger case series is needed to verify these results.