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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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Early oral cancer is preferably treated by surgery. Its complete removal is essential for locoregional control and disease-free survival. Inadequate resection margins require adjuvant therapy such as re-resection or (chemo)radiation, that causes extra morbidity and oral discomfort. Intraoral ultrasonography (US) is reported to be of value in determining tumor thickness. Intraoperative visualization of the tumor may facilitate the resection and ensure adequate surgical margins. Furthermore, accurate prediction of tumor thickness could help determine the treatment strategy of the clinically node-negative neck, as thickness and depth of invasion are predictors of cervical metastasis as well as prognosticators of survival. The 8th edition of the American Joint Committee on Cancer staging system for oral squamous cell carcinoma has included depth of invasion as parameter for cT-stage. The aim of this review is to analyze the accuracy of intraoral US in determining tumor thickness in oral cancer. A systematic search was conducted, and the quality of the included papers was assessed using the QUADAS-2 tool for diagnostic accuracy studies. Subsequently, a meta-analysis was performed on the available individual participant data of 240 patients. Most of the twelve included studies focused on T1-2 tongue cancer (n = 129). Meta-analysis showed a high correlation in tumor thickness within this subgroup as measured by intraoral US and histopathology (r = 0.82, p < .001), with minor overestimation of 0.5 mm on US. It is concluded that intraoral US is very accurate in determining tumor thickness in early oral tongue cancer., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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., (© 2015 Wiley Periodicals, Inc.)

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., (© 2014 Wiley Periodicals, Inc.)

Background: GTV delineation is the first crucial step in radiotherapy and requires high accuracy, especially with the growing use of highly conformal and adaptive radiotherapy techniques. If GTV delineations of observers concord, they are considered to be of high accuracy. The aim of the study is to determine the interobserver agreement for GTV delineations of supraglottic laryngeal carcinoma on CT and on CT combined with MR-images and to determine the effect of adding MR images to CT-based delineation on the delineated volume and the interobserver agreement., Methods: Twenty patients with biopsy proven T1-T4 supraglottic laryngeal cancer, treated with curative intent were included. For all patients a contrast enhanced planning CT and a 1.5-T MRI with gadolinium were acquired in the same head-and-shoulder mask for fixation as used during treatment. For MRI, a two element surface coil was used as a receiver coil. Three dedicated observers independently delineated the GTV on CT. After an interval of 2 weeks, a set of co-registered CT and MR-images was provided to delineate the GTV on CT. Common volumes (C) and encompassing volumes (E) were calculated and C/E ratios were determined for each pair of observers. The conformity index general (CIgen) was used to quantify the interobserver agreement., Results: In general, a large variation in interobserver agreement was found for CT (range: 0.29-0.77) as well as for CT-MR delineations (range: 0.17-0.80). The mean CIgen for CT (0.61) was larger compared to CT-MR (0.57) (p = 0.032). Mean GTV volume delineated on CT-MR (6.6 cm(3)) was larger compared to CT (5.6 cm(3)) (p = 0.002)., Conclusion: Delineation on CT with co-registered MR-images resulted in a larger mean GTV volume and in a decrease in interobserver agreement compared to CT only delineation for supraglottic laryngeal carcinoma.

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.

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.

Background and Purpose: Evaluation of the variation in tumor growth rate and the influence of tumor growth rate on disease free survival (DFS) and overall survival (OS) in laryngeal squamous cell carcinoma (LSCC)., Material and Methods: We delineated tumor volume on a diagnostic and planning CT scan in 131 patients with laryngeal squamous cell carcinoma and calculated the tumor growth rate. Primary endpoint was DFS. Follow up data were collected retrospectively., Results: A large variation in tumor growth rate was seen. When dichotomized with a cut-off point of -0.3 ln(cc/day), we found a significant association between high growth rate and worse DFS (p = 0.008) and OS (p = 0.013). After stepwise adjustment for potential confounders (age, differentiation and tumor volume) this significant association persisted. However, after adjustment of N-stage association disappeared. Exploratory analyses suggested a strong association between N-stage and tumor growth rate., Conclusions: In laryngeal squamous cell carcinoma, there is a large variation in tumor growth rate. This tumor growth rate seems to be an important factor in disease free survival and OS. This tumor growth rate is independent of age, differentiation and tumor volume associated with DFS, but N-stage seems to be a more important risk factor., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Tumor volume is a significant prognostic factor in the treatment of malignant head and neck tumors. Unfortunately, it is not routinely measured because of the workload involved., Methods: Twenty-one patients, between 2009 and 2010, were studied. Dynamic contrast-enhanced MRI (DCE-MRI) at 3.0T was performed. A workstation previously developed for semi-automated segmentation of breast cancers on DCE-MRI was used to segment the head and neck cancers. The Pearson correlation analysis was used to assess the agreement between volumetric measurements and the manually derived gross tumor volume (GTV)., Results: In 90.5% of the patients (19 of 21) correlation could be made between DCE-MRI and the manually derived GTV. The Pearson correlation coefficient between the automatically derived tumor volume at DCE-MRI and the manually derived GTVs was R(2) = 0.95 (p < .001)., Conclusion: Semi-automated tumor volumes on DCE-MRI were representative of those derived from the manually derived GTV (R(2) = 0.95; p < .001)., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Tumor volume is an important predictor of outcome in radiotherapy alone. Its significance in concomitant chemoradiation (CCRT) is much less clear. We analyzed the prognostic value of primary tumor volume for advanced head and neck squamous cell carcinoma (HNSCC) treated with CCRT., Methods: Three hundred sixty patients treated with definitive CCRT for advanced HNSCC were selected. The pretreatment MRI or CT scan was used to calculate the primary tumor volume. Median follow-up was 19.8 months., Results: The average primary tumor volume was 37.0 cm³ (range, 2.1-182.7 cm³; median, 28.7 cm³). Multivariate analysis showed a significant effect of tumor volume on local control. The hazard ratio for a local recurrence increased by 14% per 10 cm³ volume increase (95% CI, 8% to 21%). There was no significant independent effect of T and N status on local control., Conclusion: For advanced HNSCC, tumor volume is more powerful for predicting outcome after CCRT than TNM status., (Copyright © 2010 Wiley Periodicals, Inc.)

Background: Ultrasound-guided fine-needle aspiration cytology (US-FNAC) can be used to diminish the risk of missing occult metastases and for early detection during follow-up., Methods: A retrospective study was performed in 163 surgically treated patients without palpable neck nodes (N0). One hundred twenty-six patients underwent planned elective neck dissections, and 37 were planned for a wait-and-see strategy, but preoperative US-FNAC could change this policy if metastases were detected., Results: In the elective neck dissection group, US-FNAC had a sensitivity of 39%, whereas in the wait-and-see group, the sensitivity was 18%. The 5-year survival in the wait-and-see group did not differ from the patients with early oral cancer who underwent an elective neck dissection., Conclusion: Although the sensitivity of US-FNAC in this study is low, especially in small oral cancer, the prognosis in the wait-and-see group is not affected. However, a wait-and-see strategy is only advantageous to a minority of the patients., ((c) 2008 Wiley Periodicals, Inc. Head Neck, 2008.)

Background: The purpose of this study was to evaluate the prognostic value of tumor volume in head and neck squamous cell carcinoma treated with chemoradiation., Methods: Forty-six patients were treated with radiotherapy and cisplatin (6 mg/m(2) IV x 20, daily). Baseline primary tumor volume was recorded from MRI scans. The prognostic impact of tumor volume and other factors for locoregional control, disease-free survival (DFS), and overall survival (OS) was tested., Results: Mean tumor volume was 28 cm(3) (median 23 cm(3); range, 3-112). The locoregional control rate at 3 years was 81% for patients with tumor volumes or = median (p = .036). At multivariate analysis, it appeared that tumor volume remained an independent determinant of locoregional control and survival when adjusted for other factors., Conclusions: In advanced-stage head and neck squamous cell carcinoma treated with concurrent chemoradiation, primary tumor volume is associated with locoregional control and survival. Larger studies are needed to confirm whether incorporation of tumor volume in the staging system improves prediction of treatment outcome and can serve as a tool to guide treatment options.

Background: The objectives of this prospective trial were to evaluate the diagnostic accuracy and predictive value of magnetic resonance imaging (MRI) and to use MRI evaluation under general anesthesia (EGA) 6 to 8 weeks after chemoradiation to determine local control., Methods: Eighty-two consecutive patients with advanced-stage squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or supraglottic larynx were treated with selective targeted chemoradiation. All patients who completed treatment and survived had a minimum follow-up of 3 years. MRI and EGA were performed from 6 to 8 weeks after treatment. Posttreatment MRI findings were compared with pretreatment MRI findings and were graded for risk of local recurrence/residual disease on a 4-point scale. The diagnosis of treatment failure was based on tissue biopsies, which were obtained during EGA or later during follow-up. The predictive value of MRI was analyzed by using a Cox proportional hazards model., Results: Only 1 patient with MRI Grade 0 or 1 findings (discrete mass < 10 mm; n = 62 patients) had residual disease 6 to 8 weeks after treatment that was detected during EGA. In 5 patients with MRI findings of Grade 2a and 2b (mass > 10 mm; n = 20 patients), residual disease was detected. After 2 years, 23 patients had a local failure (28%). Twelve local failures were found among 62 patients who had MRI findings of Grade 0 and 1. Posttreatment MRI emerged as an independent predictive factor (hazard ratio, 3.0; P = .014) for local control., Conclusions: Posttreatment MRI studies provided predictive information on local control in addition to pretreatment predictors. In patients with focal masses < 10 mm, the combination of response evaluation under general anesthesia and posttreatment MRI from 6 to 8 weeks after chemoradiation hardly provided more information on the local control than posttreatment MRI alone., (2006 American Cancer Society)

Background: Concurrent chemoradiation is being used increasingly to treat patients with advanced-stage head and neck carcinoma. In the current study, a clinical nomogram was developed to predict local control and overall survival rates for individual patients who will undergo chemoradiation., Methods: Ninety-two consecutive patients with UICC TNM Stage III/IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and supraglottic larynx were treated with selective-targeted chemoradiation (acronym: RADPLAT). All living patients had a minimum follow-up of 2 years. In addition to general factors, the following parameters were analyzed in a multivariable analysis: primary tumor volume, lymph node tumor volume, total tumor volume, lowest involved neck level, comorbidity, pretreatment hemoglobin level, pretreatment weight loss, and unilateral/bilateral intraarterial infusion. Relevant factors for local control and survival were analyzed using the Cox proportional hazards model., Results: At 5 years, the local control and overall survival rates for the whole group were 60% and 38%, respectively. Primary tumor volume (hazard ratio [HR], 1.03; P = 0.01) and unilateral infusion (HR, 5.05; P = 0.004) were found to influence local control significantly. Using tumor volume as a continuous variable, an adjusted risk ratio of 1.026 was found, indicating that each 1-cm(3) increase in volume was associated with a 2.6% decrease in probability of local control. Primary tumor volume (HR, 1.01; P = 0.003), comorbidity (American Society of Anesthesiologists [ASA] physical status 1 vs. > 1; HR, 2.47; P = 0.01), lowest involved neck level (HR, 3.45; P = 0.007), and pretreatment weight loss > 10% (HR, 2.04; P = 0.02) were found to be significant predictors of worse overall survival. Variables from the multivariable analysis were used to develop a nomogram capable of predicting local control and overall survival., Conclusions: Tumor volume was found to play a significant role in predicting local control and overall survival in patients with advanced-stage head and neck carcinoma who were treated with targeted chemoradiation. The nomograms may be useful for pretreatment selection of patients with advanced-stage head and neck carcinoma.