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

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.

The accuracy of target delineation in laryngeal and hypopharyngeal cancer.

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.

Towards mid-position based Stereotactic Body Radiation Therapy using online magnetic resonance imaging guidance for central lung tumours.

Background and purpose: Central lung tumours can be treated by magnetic resonance (MR)-guided radiotherapy. Complications might be reduced by decreasing the Planning Target Volume (PTV) using mid-position (midP)-based planning instead of Internal Target Volume (ITV)-based planning. In this study, we aimed to verify a method to automatically derive patient-specific PTV margins for midP-based planning, and show dosimetric robustness of midP-based planning for a 1.5T MR-linac. Materials and methods: Central(n = 12) and peripheral(n = 4) central lung tumour cases who received 8x7.5 Gy were included. A midP-image was reconstructed from ten phases of the 4D-Computed Tomography using deformable image registration. The Gross Tumor Volume (GTV) was delineated on the midP-image and the PTV margin was automatically calculated based on van Herk's margin recipe, treating the standard deviation of all Deformation Vector Fields, within the GTV, as random error component. Dosimetric robustness of midP-based planning for MR-linac using automatically derived margins was verified by 4D dose-accumulation. MidP-based plans were compared to ITV-based plans. Automatically derived margins were verified with manually derived margins. Results: The mean D95% target coverage in GTV + 2 mm was 59.9 Gy and 62.0 Gy for midP- and ITV-based central lung plans, respectively. The mean lung dose was significantly lower for midP-based treatment plans (difference:-0.3 Gy; p < 0.042 ). Automatically derived margins agreed within one millimeter with manually derived margins. Conclusions: This retrospective study indicates that mid-position-based treatment plans for central lung Stereotactic Body Radiation Therapy yield lower OAR doses compared to ITV-based treatment plans on the MR-linac. Patient-specific GTV-to-PTV margins can be derived automatically and result in clinically acceptable target coverage.

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

BACKGROUND: For accurate target definition, we determined margins for the clinical target volume (CTV) for laryngeal and hypopharyngeal cancer in computed tomography (CT, 4.3 mm), magnetic resonance imaging (MR, 6.1 mm) and fluorodeoxyglucose (FDG)-positron emission tomography (PET, 5.2 mm). Previously, we used Hematoxylin-eosin (HE) stained whole-mount sections of total laryngectomy specimens as gold standard to define CTV margins. In the present study, we verified the HE-based tumor delineation with staining for pan-cytokeratin, specific for squamous cell carcinoma. METHODS: Twenty-seven patients with a T3/T4 laryngeal hypopharyngeal tumor were included. From each patient, a total laryngectomy specimen was obtained. Four subsequent 3-mm thick slices containing tumor were selected of which 4-µm thick whole-mount sections were obtained and stained with HE and for pan-cytokeratin CK-AE1/3. Tumors were microscopically delineated on both sections by an experienced head-and-neck pathologist. Tumor delineations were compared using the conformity index (CI) and the distance between both contours. RESULTS: The CI between HE-based and CK-AE1/3-based tumor delineations was 0.87. The maximum and 95th percentile (p95) extent of the HE-based tumor delineations from the CK-AE1/3-based tumor delineations were 1.7 mm and 0.7 mm, respectively. The maximum and p95 extent of the CK-AE1/3-based tumor delineations from the HE-based tumor delineations was 1.9 mm and 0.8 mm, respectively. CONCLUSIONS: Histopathological assessment of tumor outline on standard HE-stained sections is comparable to microscopic tumor extent based on squamous cell specific pan-cytokeratin staining. Therefore, CTV margins based on HE based tumor contour will be adequate.

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.

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.