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Purpose: To develop and evaluate a patch‐based convolutional neural network (CNN) to generate synthetic computed tomography (sCT) images for magnetic resonance (MR)‐only workflow for radiotherapy of head and neck tumors. A patch‐based deep learning method was chosen to improve robustness to abnormal anatomies caused by large tumors, surgical excisions, or dental artifacts. In this study, we evaluate whether the generated sCT images enable accurate MR‐based dose calculations in the head and neck region. Methods: We conducted a retrospective study on 34 patients with head and neck cancer who underwent both CT and MR imaging for radiotherapy treatment planning. To generate the sCTs, a large field‐of‐view T2‐weighted Turbo Spin Echo MR sequence was used from the clinical protocol for multiple types of head and neck tumors. To align images as well as possible on a voxel‐wise level, CT scans were nonrigidly registered to the MR (CTreg). The CNN was based on a U‐net architecture and consisted of 14 layers with 3 × 3 × 3 filters. Patches of 48 × 48 × 48 were randomly extracted and fed into the training. sCTs were created for all patients using threefold cross validation. For each patient, the clinical CT‐based treatment plan was recalculated on sCT using Monaco TPS (Elekta). We evaluated mean absolute error (MAE) and mean error (ME) within the body contours and dice scores in air and bone mask. Also, dose differences and gamma pass rates between CT‐ and sCT‐based plans inside the body contours were calculated. Results: sCT generation took 4 min per patient. The MAE over the patient population of the sCT within the intersection of body contours was 75 ± 9 Hounsfield Units (HU) (±1 SD), and the ME was 9 ± 11 HU. Dice scores of the air and bone masks (CTreg vs sCT) were 0.79 ± 0.08 and 0.70 ± 0.07, respectively. Dosimetric analysis showed mean deviations of −0.03% ± 0.05% for dose within the body contours and −0.07% ± 0.22% inside the >90% dose volume. Dental artifacts obscuring the CT could be circumvented in the sCT by the CNN‐based approach in combination with Turbo Spin Echo (TSE) magnetic resonance imaging (MRI) sequence that typically is less prone to susceptibility artifacts. Conclusions: The presented CNN generated sCTs from conventional MR images without adding scan time to the acquisition. Dosimetric evaluation suggests that dose calculations performed on the sCTs are accurate, and can therefore be used for MR‐only radiotherapy treatment planning of the head and neck. [ABSTRACT FROM AUTHOR]

Background Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (SCC) have a better survival than with HPV-negative oropharyngeal SCC. An 18F-fluorodeoxyglucose positron emission tomography-CT (18F-FDG-PET-CT) may also provide prognostic information. We evaluated glycolytic characteristics in HPV-negative and HPV-positive oropharyngeal SCC. Methods Forty-four patients underwent pretreatment 18F-FDG-PET-CT. Standardized uptake values (SUVs) and metabolic active tumor volumes (MATVs) were determined for primary tumors. HPV status was determined with p16 immunostaining, followed by high-risk HPV DNA detection on the positive cases. Results Twenty-seven patients were HPV-positive (61.4%). Median MATV was 2.8 mL (range = 1.6-5.1 mL) for HPV-positive and 6.0 mL (range = 4.4-18.7 mL) for HPV-negative tumors ( p < .001). SUV values are volume dependent (partial volume effect), therefore, MATV was included as covariate in multivariate analysis. In this multivariate analysis, the maximum SUV in HPV-positive tumors was 3.9 units lower than in HPV-negative tumors ( p = .01). Conclusion The 18F-FDG-PET-CT parameters are lower in HPV-positive than in HPV-negative patients. Low pretreatment SUV values in HPV-positive oropharyngeal SCC may be at least partly explained by HPV-induced tumor changes. © 2015 Wiley Periodicals, Inc. Head Neck 38: 529-535, 2016 [ABSTRACT FROM AUTHOR]

Purpose: Interactive optimization during treatment planning requires intermittent adjustment of organ-at-risk (OAR) objectives relative to the dose-volume histogram line. This is a labor-intensive process and the resulting plans are prone to variations in quality. The authors' in-house developed approach to automated interactive optimization (AIO) automatically moves the mouse cursor to adjust the position of on-screen optimization objectives. This allows for the use of more objectives per OAR and results in a more frequent and consistent adjustment of these objectives during optimization. The authors report a detailed evaluation of AIO performance in support of its implementation for routine head and neck cancer (HNC) planning and an evaluation for locally advanced lungcancer (LC) planning which requires a different optimization strategy. Methods: Volumetric modulated arc therapy AIO plans (APs) were created for 70 HNC patients with a simultaneously integrated boost and 20 LC patients and benchmarked against their respective manually interactively optimized plans (MPs). The same set of optimization objectives and priorities was used for all APs, although planning target volume (PTV) optimization priorities could be increased manually in a subsequent "continue previous optimization" calculation. HNC plans were benchmarked using mean dose to individual and composite OARs and elective/boost PTV (PTVE/PTVB) volumes receiving 95% and 107% of the prescription dose (V95% and V107%, respectively). A clinician performed blinded comparison of 20 APs and respective MPs. LC plans were compared using PTV V95%/V107%, contralateral lung (CL) volume receiving 5 Gy (V5Gy), total lung (TL)-PTV V5Gy/V20Gy, and esophagus and heart V40Gy/V60Gy/mean doses. Results: For HNC, statistically significant improvements in sparing of all OARs, except for the ipsilateral submandibular gland and trachea, were obtained in the APs compared to MPs. Average mean dose to oral cavity, composite salivary, and swallowing structures were 25.4/23.8, 24.2/23.2, and 29.5/25.5 Gy, respectively, for the MPs/APs. PTV heterogeneity was similar: in the APs, PTVB V95% was 0.2% higher while PTV B/PTV E V107% was 0.4%/1.0% lower. In 19 out of 20 HNC patients, the clinician preferred the AP, mainly because of better OAR sparing and PTV dose homogeneity. For LC, APs had a significantly lower CL V5Gy (6.1%), heart mean dose/V60Gy (0.9 Gy/1.2%) and esophagus mean dose/V60Gy (0.9 Gy/2.8%), a nonsignificantly higher TL V20Gy (1.4%), and a slight, but significantly higher dose deposition to the body. PTV dose coverage and homogeneity were similar in the APs and MPs. AIO was considered sufficiently robust for clinical use in LC. Conclusions: HNC and LC APs were at least as good as, and often of improved quality over MPs. To date, AIO has been clinically implemented for HNC planning. [ABSTRACT FROM AUTHOR]

Background The prognostic and predictive value of the proliferation marker Ki-67 was investigated in a randomized trial comparing accelerated radiotherapy with carbogen breathing and nicotinamide (ARCON) to accelerated radiotherapy in laryngeal carcinoma. Methods Labeling index of Ki-67 (Li Ki-67) in immunohistochemically stained biopsies and the colocalization with carbonic anhydrase IX (CAIX) were related to tumor control and patient survival. Results On average, node-positive patients had a higher Li Ki-67 (median 14% vs 8%; p < .01). In patients with a high Li Ki-67, the 5-year regional control and metastases-free survival were 79% versus 96% ( p < .01) and 71% versus 88% ( p = .05) for accelerated radiotherapy and ARCON, respectively. The 5-year local control and disease-specific survival were not significantly different. Patients with low Ki-67 expression had an excellent outcome with accelerated radiotherapy alone. Conclusion Patients with laryngeal carcinomas with high proliferative activity are at increased risk of regional and distant metastases formation. This risk can be reduced by treatment with ARCON. © 2014 Wiley Periodicals, Inc. Head Neck 37: 171-176, 2015 [ABSTRACT FROM AUTHOR]

Purpose: Conventional radiotherapy typically aims for homogenous dose in the planning target volume (PTV) while sparing organs at risk (OAR). The authors quantified and characterized the trade-off between PTV dose inhomogeneity (IH) and OAR sparing in complex head and neck volumetric modulated arc therapy plans. Methods: Thirteen simultaneous integrated boost plans were created per patient, for ten patients. PTV boost(B)/elective(E) optimization priorities were systematically increased. IHB and IHE, defined as (100% − V95%) + V107%, were evaluated against the average of the mean dose to the combined composite swallowing and combined salivary organs (D-OARcomp). To investigate the influence of OAR size and position with respect to PTVB/E, OAR dose was evaluated against a modified Euclidean distance (DMB/DME) between OAR and PTV. Results: Although the achievable D-OARcomp for a given level of PTV IH differed between patients, excellent logarithmic fits described the D-OARcomp/IHB and IHE relationship in all patients (mean R2 of 0.98 and 0.97, respectively). Allowing an increase in average IHB and IHE over a clinically acceptable range, e.g., from 0.4% ± 0.5% to 2.0% ± 2.0% and 6.9% ± 2.8% to 14.8% ± 2.7%, respectively, corresponded to a decrease in average dose to the composite salivary and swallowing structures from 30.3 ± 6.5 to 23.6 ± 4.7 Gy and 32.5 ± 8.3 to 26.8 ± 9.3 Gy. The increase in PTVE IH was mainly accounted for by an increase in V107, by on average 5.9%, rather than a reduction in V95, which was on average only 2%. A linear correlation was found between the OAR dose to composite swallowing structures and contralateral parotid and submandibular gland, with DME ( R2 = 0.83, 0.88, 0.95). Only mean ipsilateral parotid dose correlated with DMB ( R2 = 0.87). Conclusions: OAR sparing is highly dependent on the permitted PTVB/E IH. PTVE IH substantially influences OAR doses. These results are relevant for clinical practice and for future automated treatment-planning strategies. [ABSTRACT FROM AUTHOR]

Background The objective of this study was to evaluate the effectiveness and safety of our careful observational strategy and neck dissections and the accuracy of ultrasound-guided fine-needle aspiration cytology, and to determine the prognostic factors for outcome and regional control after primary chemoradiation. Diagnostic evaluation of the regional status after concurrent chemoradiation for advanced head and neck cancer remains difficult, and the indications for a salvage neck dissection and its extent are not clearly defined. Methods In a series of 540 patients, there was suspicion of regional residual or recurrent disease after chemoradiation in 61 patients who underwent 68 salvage neck dissections and 68 patients who were considered unresectable. For the patients with salvage neck dissection, the accuracy of ultrasound-guided fine-needle aspiration cytology was determined. Disease control in the neck, disease-specific and overall survival, and parameters that may have prognostic value for the outcome were evaluated. Results Neck dissection specimens contained viable tumor in 26 (43%) patients. Of these, 13 had selective neck dissections and 13 modified radical neck dissections. Ultrasound-guided fine-needle aspiration cytology had a sensitivity of 80% and specificity of 42%. Nine patients developed a regional recurrence after salvage neck dissection (5 located in contralateral neck). Five-year regional control and overall survival rates were 79% and 36%, respectively. Significant prognostic factors for overall survival were surgical margins and “residual versus recurrent disease” in multivariate analysis. Conclusion Considering the good regional control rate and the high rate of unnecessary neck dissections with a theoretical planned neck dissection strategy, we conclude that a careful observational strategy is worthwhile and safe. For the evaluation of radiation treatment response, ultrasound-guided fine-needle aspiration cytology has a low specificity. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [ABSTRACT FROM AUTHOR]

Background. The aim of the study was to analyze speech outcome for patients with advanced oral/oropharyngeal cancer treated with reconstructive surgery and adjuvant radiotherapy. Methods. Speech tests (communicative suitability, intelligibility, articulation, nasality, and consonant errors) were performed in a control group and in patients before treatment (n = 76), and 6 months (n = 51) and 12 months (n = 42) after treatment. Results. Speech tests were significantly worse for patients before and after treatment compared with the controls. Speech did not improve between 6 and 12 months. After treatment, patients with T3–4 tumors showed a significantly worse score for communicative suitability, intelligibility, and articulation than patients with T2 tumors. No significant differences were found for subsites after treatment, although patients with mobile tongue tumors showed the best results. Conclusion. Speech difficulties are significant, and with the knowledge of this study better counseling and vigilance as to speech difficulties may be possible in patients undergoing treatment for oral/oropharyngeal cancer. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX–XXX, 2005 [ABSTRACT FROM AUTHOR]