J. Caldas-Magalhaes

Diffusion-weighted MR Imaging in Laryngeal and Hypopharyngeal Carcinoma: Association between Apparent Diffusion Coefficient and Histologic Findings

PURPOSE To investigate the relationship between the histologic characteristics of head and neck squamous cell carcinoma and apparent diffusion coefficient (ADC) at diffusion-weighted magnetic resonance (MR) imaging. MATERIALS AND METHODS The institutional ethics committee approved this study and waived informed consent. In head and neck squamous cell carcinoma, local failure after chemotherapy and/or radiation therapy correlates with pretreatment ADC. However, the histopathologic basis of this correlation remains unclear. In this study, 16 patients with head and neck squamous cell carcinoma were enrolled (median age, 60 years; range, 49-78 years). Before undergoing total laryngectomy, patients underwent 1.5-T diffusion-weighted MR imaging. After resection, whole-mount hematoxylin-eosin-stained sections were registered to the MR images. Cellular density; nuclear, cytoplasmic, and stromal area; and nuclear-cytoplasmic ratio within the tumor were calculated by using image-based segmentation on four consecutive slices. Mean ADC of the corresponding tumor region was calculated. Spearman correlations between ADC and histologic characteristics were calculated. RESULTS ADC was significantly and inversely correlated with cell density (n = 16, r = -0.57, P = .02), nuclear area (n = 12, r = -0.64, P = .03), and nuclear-cytoplasmic ratio (n = 12, r = -0.77, P ≤ .01). ADC was significantly and positively correlated with percentage area of stroma (n = 12, r = 0.69, P = .01). Additionally, the percentage area of stroma was strongly interdependent with the percentage area of nuclei (n = 12, r = -0.97, P ≤ .01). CONCLUSION ADC was significantly correlated with cellularity, stromal component, and nuclear-cytoplasmic ratio. The positive correlation of ADC and stromal component suggests that the poor prognostic value of high pretreatment ADC might partly be attributed to the tumor-stroma component, a known predictor of local failure.

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.

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.

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.