Pretreatment ADC is not a prognostic factor for local recurrences in head and neck squamous cell carcinoma when clinical T-stage is known.

OBJECTIVES: Pretreatment identification of radio-insensitive head and neck squamous cell carcinomas (HNSCC) would affect treatment modality selection. The apparent diffusion coefficient (ADC) of a tumor could be a predictor of local recurrence. However, little is known about its prognostic value next to known factors such as clinical T-stage. The aim of the present study is to determine the added value of pretreatment ADC to clinical T-stage as a prognostic factor for local recurrence. METHODS: This retrospective cohort study included 217 patients with HNSCC treated with (chemo)radiotherapy between April 2009 and December 2015. All patients underwent diffusion-weighted MRI prior to treatment. Median ADC values of all tumors were obtained using a semi-automatic delineation method. Univariate models containing ADC and T-stage were compared with a multivariable model containing both variables. RESULTS: Fifty-eight patients experienced a local recurrence within 3 years. On average, the ADC value in the group of patients with a recurrence was 1.01 versus 1.00 (10-3 mm2/s) in the group without a recurrence. Univariate analysis showed no significant association between tumor ADC and local recurrence within 3 years after (chemo)radiotherapy (p = 0.09). Cox regression showed that clinical T-stage was an independent predictor of local recurrence and adding ADC to the model did not increase its performance. CONCLUSION: Pretreatment ADC has no added value as a prognostic factor for local recurrence to clinical T-stage. KEY POINTS: • Pretreatment identification of head and neck squamous cell carcinoma patients who do not benefit from (chemo)radiotherapy could improve personalized cancer care. • The apparent diffusion coefficient (ADC) obtained from diffusion-weighted MRI has been reported to be a prognostic factor for local recurrence. • In this study, ADC has no added value as a prognostic factor compared with clinical T-stage.

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.

Defining the protruding ear.

OBJECTIVE: Although protruding ears are one of the most frequently occurring congenital deformities in the craniofacial area, there is no clear consensus in literature as to the definition. Our aim was to provide a clear delineation for the definition of prominent ears, deduced from the anthropometry of normal (nonprotruding) ears. METHODS: We performed a prospective cohort study to assess the anatomy of the normal auricle in children using computer-assisted anthropometry in photographs of 102 children aged 5 to 18 years. We compared the anatomy to retrospectively assess photographs of 44 patients who were listed for prominent ear correction. RESULTS: Our results show that protrusion differs statistically between sexes. In view of these data, an ear could be defined as prominent when the upper protrusion exceeds 21.5 mm or the lower protrusion exceeds 20.0 mm in boys and the upper protrusion exceeds 17.5 mm or the lower protrusion exceeds 15.5 mm in girls. Using these demarcations, 87.5% of our operated prominent ears would qualify as a prominent ear. In addition, we found that prominent ears have larger auricular lengths and consequently larger surface measurements compared with normal ears (P = 0.001). Up to 19.3% of the normal ears showed an asymmetry of more than 3 mm concerning protrusion. CONCLUSIONS: Protrusion differs significantly between sexes. This indicates that different criteria should be used to judge protrusion in boys and girls. None of our prominent ears exceeded only the demarcation in the lower protrusion, suggesting that upper protrusion plays a larger role in the perception of prominence than lower protrusion and should therefore be the main objective of corrective otoplasty. Furthermore, the variation of asymmetry of protrusion in the normal population indicates that an often used success criteria in otoplasty of an asymmetry less than 3 mm may be too strict.

Prospective comparative study of MRI including diffusion-weighted images versus FDG PET-CT for the detection of recurrent head and neck squamous cell carcinomas after (chemo)radiotherapy.

OBJECTIVE: This prospective study aims to test if MRI including diffusion weighted images can replace FDG PET-CT in the diagnosis of patients with suspicion of local recurrent head and neck squamous cell carcinomas after (chemo)radiation. METHODS: Seventy-five patients suspected of local recurrence underwent a MRI and a FDG PET-CT. Qualitative assessment of the images was performed. Reference standard was the results of biopsy or the absence of a recurrence during follow up. RESULTS: Seventy patients were included. Fifty percent had local recurrence. FDG PET-CT had accuracy of 71% compared to 73% for MRI. The sensitivity and specificity were 97% compared to 69% and 46% compared to 77% for FDG PET-CT and MRI respectively. CONCLUSIONS: MRI showed similar diagnostic accuracy, superior specificity but inferior sensitivity compared to FDG PET-CT. Based on current results, we consider MRI including diffusion weighted sequences unable to replace FDG PET-CT as a single imaging modality when local recurrent disease of HNSCC after (C)RT is suspected.

Influence of tumor and microenvironment characteristics on diffusion-weighted imaging in oropharyngeal carcinoma: A pilot study.

OBJECTIVES: Diffusion weighted imaging (DWI) is a frequently performed MRI sequence in cancer patients. While previous studies have shown the clinical value of the apparent diffusion coefficient (ADC) for response prediction and response monitoring, less is known about the biological background of ADC. In the tumor microenvironment, hypoxia and increased proliferation of tumor cells contribute to resistance to (radio-)therapy, while high T-cell influx is related to better prognosis. We investigated the correlation between these three tissue characteristics and ADC in 20 oropharyngeal squamous cell carcinoma patients. MATERIALS AND METHODS: 20 patients with oropharyngeal squamous cell carcinoma (OPSCC) who underwent 1.5 T MRI, including DWI were included in this pilot study. Corresponding formalin-fixed paraffin-embedded tumor tissues were immunohistochemically analyzed for protein expression of hypoxia-inducible factor 1a (HIF-1a), Ki-67 and CD3. Expression of these markers was correlated with ADC. RESULTS: ADC negatively correlated with Ki-67 expression (p = .024) in tumor cells. There was a significant negative correlation between ADC and CD3-positive cell count (p = .009). No correlation was observed between HIF-1a expression and ADC. CONCLUSION: This study suggests that ADC reflects characteristics of tumor cells as well as the surrounding microenvironment. Interestingly, high tumor proliferation (a negative prognostic factor) and high T-cell influx (a beneficial prognostic factor) are both associated with a lower ADC. Further studies should be performed to correlate ADC to these histological characteristics in relation to previously known factors that affect ADC, to gain further knowledge on the role of DW-MRI in diagnostics and personalized medicine.

The interobserver agreement in the detection of recurrent HNSCC using MRI including diffusion weighted MRI.

INTRODUCTION: For the detection of local recurrences of head and neck squamous cell carcinomas (HNSCC) after (chemo)radiation, diagnostic imaging is generally performed. Diffusion weighted magnetic resonance imaging (DW-MRI) has been proven to be able to adequately diagnose the presence of cancer. However evaluation of DW-MR images for recurrences is difficult and could be subject to individual interpretation. AIM: To determine the interobserver agreement, intraobserver agreement and influence of experience of radiologists in the assessment of DW-MRI in patients clinically suspected of local recurrent HNSCC after (chemo)radiation. METHODS: Ten experienced head and neck radiologists assessed follow-up MRI including DW-MRI series of 10 patients for the existence of local recurrence on a two point decision scale (local recurrence or local control). Patients were clinically suspected for a recurrence of laryngeal (n = 3), hypopharyngeal (n = 3) or oropharyngeal (n = 4) cancer after (chemo)radiation with curative intent. Fleiss' and Cohen's Kappa were used to determine interobserver agreement and intraobserver agreement, respectively. RESULTS: Interobserver agreement was κ = 0.55. Intraobserver agreement was κ = 0.80. Prior experience within the field of radiology and with DW-MRI had no significant influence on the scoring. CONCLUSION: For the assessment of HNSCC recurrence after (chemo)radiation by DW-MRI, moderate interobserver agreement and substantial intraobserver agreement was found.

Correlation of human papillomavirus status with apparent diffusion coefficient of diffusion-weighted MRI in head and neck squamous cell carcinomas.

BACKGROUND: Identification of prognostic patient characteristics in head and neck squamous cell carcinoma (HNSCC) is of great importance. Human papillomavirus (HPV)-positive HNSCCs have favorable response to (chemo)radiotherapy. Apparent diffusion coefficient, derived from diffusion-weighted MRI, has also shown to predict treatment response. The purpose of this study was to evaluate the correlation between HPV status and apparent diffusion coefficient. METHODS: Seventy-three patients with histologically proven HNSCC were retrospectively analyzed. Mean pretreatment apparent diffusion coefficient was calculated by delineation of total tumor volume on diffusion-weighted MRI. HPV status was analyzed and correlated to apparent diffusion coefficient. RESULTS: Six HNSCCs were HPV-positive. HPV-positive HNSCC showed significantly lower apparent diffusion coefficient compared to HPV-negative. This correlation was independent of other patient characteristics. CONCLUSION: In HNSCC, positive HPV status correlates with low mean apparent diffusion coefficient. The favorable prognostic value of low pretreatment apparent diffusion coefficient might be partially attributed to patients with a positive HPV status. © 2015 Wiley Periodicals, Inc. Head Neck 38: E613-E618, 2016.

Diffusion-weighted imaging in head and neck squamous cell carcinomas: a systematic review.

BACKGROUND: The purpose of this study was for us to review diagnostic accuracy of diffusion-weighted imaging (DWI) in primary head and neck squamous cell carcinomas (HNSCCs), detection of metastatic lymph nodes, and recurrences. METHODS: A systematic review for studies concerning DWI was performed. RESULTS: Ten studies fulfilled inclusion criteria. All studies showed significant higher "apparent diffusion coefficient" (ADC) in benign compared to malignant lesions. ADC thresholds for optimal discrimination varied. In detection of primary HNSCC, the accuracy of DWI ranged from 66% to 86%. In metastatic lymph nodes, the accuracy of DWI was 85% to 91% and the negative predictive value (NPV) was higher than 91%. For recurrences, the accuracy of DWI was 78% to 100% and the NPV ranged from 77% to 100%. CONCLUSION: DWI showed consistent high accuracy and high NPV. However, available literature is sparse and varying ADC thresholds were reported. Compared to current imaging techniques, DWI showed the most potential in lymph node staging and detection of recurrences.

New insights into facial anthropometry in digital photographs using iris dependent calibration.

BACKGROUND: In facial and reconstructive surgery objective assessment of anatomy is crucial to evaluate surgical results. Photographic computer-assisted anthropometry substitutes clinical measurements. The constancy of the horizontal iris diameter (IDh) allows iris dependent calibration of photographs, replacing the need for a scale. METHODS: We performed a prospective cohort study to assess the constancy of the IDh in children. Frontal and close-up digital photographs of the eyes were taken of 100 children aged 5-18 years. The IDh was measured twice; once with a scale positioned on the forehead (IDh*(forehead)) and once with a scale positioned next to the tragus (IDh*(ear)). RESULTS: Our data confirms the constancy of the IDh in children from the age of 5, with a mean IDh*(forehead) of 11.22 ± 0.52 mm. We found no difference between gender and no variation with age. For structures that are not in the same coronal plane as the iris, an adjusted iris diameter is needed to compensate for the difference in distance from the camera. CONCLUSION: We confirm the reliability of iris dependent calibration in frontal photographs from the age of 5. This technique allows evaluation of a wide variety of pre-existing photographs that do not have a scale included, simplifies photographic conditions and facilitates long-term follow-up.