H. Ligtenberg

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.

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.

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.

Verification of HE-based CTV in laryngeal and hypopharyngeal cancer using pan-cytokeratin

Highlights • Currently clinical CTV margins lack evidence and need (histopathological) validation.• Tumor outline on HE and pan-cytokeratin staining are comparable for laryngeal cancer.• HE-based delineations can be used for histopathology based CTV-margin definition.

PV-0516: Guideline development for tumor delineation on MR-images for laryngeal and hypophargeal cancer

Conclusion: In all modalities, delineated GTVs overestimated tumor volume. Nevertheless, some tumor volume was missed in all cases. Automated delineation on PET resulted in the smallest target volume compared to manual delineation on CT and MRI, while covering an equivalent amount of tumor. This study suggests that delineation or segmentation inaccuracies can be corrected using a margin between 5.6 and 8.7 mm.

OC-0068: Comparison of GTV delineations on CT, MRI and FDG-PET of laryngeal and hypopharyngeal carcinoma with histopathology

increasingly used for response monitoring and prediction. In this study the diagnostic potential of DCE-MRI for treatment response assessment in esophageal cancer is investigated. Materials and Methods: In 12 patients receiving nCRT, DCEMRI studies were performed before treatment (pre), after 813 fractions (per) and 5-7 weeks after completion of nCRT, prior to surgery (post). After resection pathologic assessment of the tumor regression grade (TRG) was performed following the Mandard score. For analysis a distinction was made between a group of good responders (GR), defined as pCr (TRG 1) or near-pCr (TRG 2), and poor responders (noGR) with TRG ≥ 3. The primary tumor was delineated on the T2W images before, during and after nCRT. This delineated volume was contracted with an isotropic margin of 2 mm to account for residual motion and partial volume effects. Within this contracted volume mean, median and 75 percentile (P75) of the AUC of the contrast agent concentration was calculated. Here, the AUC was defined as the integral over the concentration curve (60 seconds, starting at inflow of contrast agent). Results: In 4 patients (33%) pCR was found and a total of 5 patients (42%) showed a good response. Initial P75 AUC values were the same across GR and noGR. Relative changes in mean, median and P75 AUC between pre and per treatment were all found to be significant across the two groups, while the same parameters comparing pre and post treatment were not significant. All noGR showed an increase in AUC comparing relative changes between pre and per treatment (fig. A), while 80% of GR remained similar or decreased. The ΔP75 pre-per was found to be most predictive (-6%±29% for GR [mean ± SD] vs. 76%±58% for noGR, p=0.005) (fig B). With a cut-off value of 17.4% an area under the ROC curve of 0.97, sensitivity of 80%, specificity of 100%, positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 88% is found.