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The definition of tumor involved volumes in patients with head and neck cancer poses great challenges with the increasing use of highly conformal radiotherapy techniques eg, volumetric modulated arc therapy and intensity modulated proton therapy. The risk of underdosing the tumor might increase unless great care is taken in the process. The information gained from imaging is increasing with both PET and MRI becoming readily available for the definition of targets. The information gained from these techniques is indeed multidimensional as one often acquire data on eg, metabolism, diffusion, and hypoxia together with anatomical and structural information. Nevertheless, much work remains to fully exploit the available information on a patient-specific level. Multimodality target definition in radiotherapy is a chain of processes that must be individually scrutinized, optimized and quality assured. Any uncertainties or errors in image acquisition, reconstruction, interpretation, and delineation are systematic errors and hence will potentially have a detrimental effect on the entire radiotherapy treatment and hence; the chance of cure or the risk of unnecessary side effects. Common guidelines and procedures create a common minimum standard and ground for evaluation and development. In Denmark, the treatment of head and neck cancer is organized within the multidisciplinary Danish Head and Neck Cancer Group (DAHANCA). The radiotherapy quality assurance group of DAHANCA organized a workshop in January 2020 with participants from oncology, radiology, and nuclear medicine from all centers in Denmark, treating patients with head and neck cancer. The participants agreed on a national guideline on imaging for target delineation in head and neck cancer radiotherapy, which has been approved by the DAHANCA group. The guidelines are available in the Supplementary. The use of multimodality imaging is being recommended for the planning of all radical treatments with a macroscopic tumor. 2-[ 18 F]FDG-PET/CT should be available, preferable in the treatment position. The recommended MRI sequences are T1, T2 with and without fat suppression, and T1 with contrast enhancement, preferable in the treatment position. The interpretation of clinical information, including thorough physical examination as well as imaging, should be done in a multidisciplinary setting with an oncologist, radiologist, and nuclear medicine specialist., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Head and neck squamous cell carcinoma (HNSCC) shows a remarkable heterogeneity between tumors, which may be captured by a variety of quantitative features extracted from diagnostic images, termed radiomics. The aim of this study was to develop and validate MRI-based radiomic prognostic models in oral and oropharyngeal cancer., Materials and Methods: Native T1-weighted images of four independent, retrospective (2005-2013), patient cohorts (n = 102, n = 76, n = 89, and n = 56) were used to delineate primary tumors, and to extract 545 quantitative features from. Subsequently, redundancy filtering and factor analysis were performed to handle collinearity in the data. Next, radiomic prognostic models were trained and validated to predict overall survival (OS) and relapse-free survival (RFS). Radiomic features were compared to and combined with prognostic models based on standard clinical parameters. Performance was assessed by integrated area under the curve (iAUC)., Results: In oral cancer, the radiomic model showed an iAUC of 0.69 (OS) and 0.70 (RFS) in the validation cohort, whereas the iAUC in the oropharyngeal cancer validation cohort was 0.71 (OS) and 0.74 (RFS). By integration of radiomic and clinical variables, the most accurate models were defined (iAUC oral cavity, 0.72 (OS) and 0.74 (RFS); iAUC oropharynx, 0.81 (OS) and 0.78 (RFS)), and these combined models outperformed prognostic models based on standard clinical variables only (p < 0.001)., Conclusions: MRI radiomics is feasible in HNSCC despite the known variability in MRI vendors and acquisition protocols, and radiomic features added information to prognostic models based on clinical parameters., Key Points: • MRI radiomics can predict overall survival and relapse-free survival in oral and HPV-negative oropharyngeal cancer. • MRI radiomics provides additional prognostic information to known clinical variables, with the best performance of the combined models. • Variation in MRI vendors and acquisition protocols did not influence performance of radiomic prognostic models.

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  mm 2 /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.

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.)

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.)

Objectives: The aim of this study is to determine a set of MRI lymph node characteristics predictive for extranodal tumor spread (ENS) in head and neck cancer patients., Methods: In 39 patients, 60 lymph nodes with on MRI a minimal axial diameter of more than 1cm or an inhomogeneous enhancement were studied. Two radiologists evaluated all MR-images for findings potentially indicative of the presence of ENS. Sensitivity, specificity and odds ratios based on logistic regression were calculated., Results: On MR-imaging, 20 lymph nodes were staged positive for ENS. On histopathology, 30 nodes were positive for ENS. In total, 14 nodes (23%) were scored differently on MR-imaging and histopathology. The MR-finding "infiltration of adjacent planes" established a specificity of 100% (lower 90% confidence bound: 91%) and sensitivity of 50% (95% confidence interval [CI]: 28-72%)., Conclusion: The MRI finding "infiltration of adjacent planes" may be high enough (100% in our study) to be used for treatment planning., (Copyright © 2013 Elsevier 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.

Purpose: To identify the anatomic structures whose damage or malfunction cause late dysphagia and aspiration after intensive chemotherapy and radiotherapy (RT) for head-and-neck cancer, and to explore whether they can be spared by intensity-modulated RT (IMRT) without compromising target RT., Methods and Materials: A total of 26 patients receiving RT concurrent with gemcitabine, a regimen associated with a high rate of late dysphagia and aspiration, underwent prospective evaluation of swallowing with videofluoroscopy (VF), direct endoscopy, and CT. To assess whether the VF abnormalities were regimen specific, they were compared with the VF findings of 6 patients presenting with dysphagia after RT concurrent with high-dose intra-arterial cisplatin. The anatomic structures whose malfunction was likely to cause each of the VF abnormalities common to both regimens were determined by literature review. Pre- and posttherapy CT scans were reviewed for evidence of posttherapy damage to each of these structures, and those demonstrating posttherapy changes were deemed dysphagia/aspiration-related structures (DARS). Standard three-dimensional (3D) RT, standard IMRT (stIMRT), and dysphagia-optimized IMRT (doIMRT) plans in which sparing of the DARS was included in the optimization cost function, were produced for each of 20 consecutive patients with advanced head-and-neck cancer., Results: The posttherapy VF abnormalities common to both regimens included weakness of the posterior motion of the base of tongue, prolonged pharyngeal transit time, lack of coordination between the swallowing phases, reduced elevation of the larynx, and reduced laryngeal closure and epiglottic inversion, contributing to a high rate of aspiration. The anatomic structures whose malfunction was the likely cause of each of these abnormalities, and that also demonstrated anatomic changes after RT concurrent with gemcitabine doses associated with dysphagia and aspiration, were the pharyngeal constrictor muscles (median thickness near midline 2.5 mm before therapy vs. 7 mm after therapy; p = 0.001), the supraglottic larynx (median thickness, 2 mm before therapy vs. 4 mm after therapy; p < 0.001), and, similarly, the glottic larynx. The constrictors and the glottic and supraglottic larynx were, therefore, deemed the DARS. The lowest maximal dose delivered to a stricture volume was 50 Gy. Reducing the volumes of the DARS receiving > or =50 Gy (V(50)) was, therefore, a planning and evaluation goal. Compared with the 3D plans, stIMRT reduced the V(50) of the pharyngeal constrictors by 10% on average (range, 0-36%, p < 0.001), and doIMRT reduced these volumes further, by an additional 10% on average (range, 0-38%; p <0.001). The V(50) of the larynx (glottic + supraglottic) was reduced marginally by stIMRT compared with 3D (by 7% on average, range, 0-56%; p = 0.054), and doIMRT reduced these volumes by an additional 11%, on average (range, 0-41%; p = 0.002). doIMRT reduced laryngeal V(50) compared with 3D, by 18% on average (range 0-61%; p = 0.001). Certain target delineation rules facilitated sparing of the DARS by IMRT. The maximal DARS doses were not reduced by IMRT because of their partial overlap with the targets. stIMRT and doIMRT did not differ in target doses, parotid gland mean dose, spinal cord, or nonspecified tissue maximal dose., Conclusions: The structures whose damage may cause dysphagia and aspiration after intensive chemotherapy and RT are the pharyngeal constrictors and the glottic and supraglottic larynx. Compared with 3D-RT, moderate sparing of these structures was achieved by stIMRT, and an additional benefit, whose extent varied among the patients, was gained by doIMRT, without compromising target doses. Clinical validation is required to determine whether the dosimetric gains are translated into clinical ones.

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.

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. [ABSTRACT FROM AUTHOR]