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Purpose: To create a dose‐response model that predicts lung ventilation change following radiation therapy, and examine the effects of out‐of‐phase ventilation. Methods: The dose‐response model was built using 27 human subjects who underwent radiation therapy (RT) from an IRB‐approved trial. For each four‐dimensional computed tomography, two ventilation maps were created by calculating the N‐phase local expansion ratio (LERN) using most or all breathing phases and the 2‐phase LER (LER2) using only the end inspiration and end expiration breathing phases. A polynomial regression model was created using the LERN ventilation maps pre‐RT and post‐RT and dose distributions for each subject, and crossvalidated with a leave‐one‐out method. Further validation of the model was performed using 15 additional human subjects using common statistical operating characteristics and gamma pass rates. Results: For voxels receiving 20 Gy or greater, there was a significant increase from 52% to 59% (P = 0.03) in the gamma pass rates of the LERN model predicted post‐RT Jacobian maps to the actual post‐RT Jacobian maps, relative to the LER2 model. Additionally, accuracy significantly increased (P = 0.03) from 68% to 75% using the LERN model, relative to the LER2 model. Conclusions: The LERN model was significantly more accurate than the LER2 model at predicting post‐RT ventilation maps. More accurate post‐RT ventilation maps will aid in producing a higher quality functional avoidance treatment plan, allowing for potentially better normal tissue sparing. [ABSTRACT FROM AUTHOR]

Background: The mechanistic target of rapamycin (MTOR) plays a key role in regulating cell growth and metabolism and is commonly overexpressed in head and neck cancer (HNSCC). This study investigated the association of MTOR with clinical outcome in human papilloma virus (HPV) positive and negative HNSCC patients treated by chemoradiation. Methods: A tissue microarray (TMA) consisting of cores from 109 HNSCC patients treated by definitive chemoradiation was constructed and stained with antibodies against p16 and MTOR and expression correlated with clinicopathological features and clinical outcome. Results: MTOR varied widely between tumor cores and was not associated with HPV status or clinicopathological features. There was a positive correlation with pre‐treatment FDG uptake. (P =.01). In HPV negative patients, MTOR predicted for shorter locoregional control (P =.02), diseases free survival (P =.02), and overall survival (P =.04). MTOR expression was not associated with outcome in HPV positive patients. Conclusions: Prognostic significance of MTOR expression depends on HPV status. [ABSTRACT FROM AUTHOR]

Purpose: To develop and evaluate the feasibility of deep learning approaches for MR‐based treatment planning (deepMTP) in brain tumor radiation therapy. Methods and materials: A treatment planning pipeline was constructed using a deep learning approach to generate continuously valued pseudo CT images from MR images. A deep convolutional neural network was designed to identify tissue features in volumetric head MR images training with co‐registered kVCT images. A set of 40 retrospective 3D T1‐weighted head images was utilized to train the model, and evaluated in 10 clinical cases with brain metastases by comparing treatment plans using deep learning generated pseudo CT and using an acquired planning kVCT. Paired‐sample Wilcoxon signed rank sum tests were used for statistical analysis to compare dosimetric parameters of plans made with pseudo CT images generated from deepMTP to those made with kVCT‐based clinical treatment plan (CTTP). Results: deepMTP provides an accurate pseudo CT with Dice coefficients for air: 0.95 ± 0.01, soft tissue: 0.94 ± 0.02, and bone: 0.85 ± 0.02 and a mean absolute error of 75 ± 23 HU compared with acquired kVCTs. The absolute percentage differences of dosimetric parameters between deepMTP and CTTP was 0.24% ± 0.46% for planning target volume (PTV) volume, 1.39% ± 1.31% for maximum dose and 0.27% ± 0.79% for the PTV receiving 95% of the prescribed dose (V95). Furthermore, no significant difference was found for PTV volume (P = 0.50), the maximum dose (P = 0.83) and V95 (P = 0.19) between deepMTP and CTTP. Conclusions: We have developed an automated approach (deepMTP) that allows generation of a continuously valued pseudo CT from a single high‐resolution 3D MR image and evaluated it in partial brain tumor treatment planning. The deepMTP provided dose distribution with no significant difference relative to a kVCT‐based standard volumetric modulated arc therapy plans. [ABSTRACT FROM AUTHOR]

Objective We evaluated the ability of the American Joint Committee on Cancer (AJCC) seventh edition staging system to prognosticate the overall survival of patients with human papillomavirus (HPV)-positive laryngeal squamous cell carcinoma. Study Design Retrospective analysis. Setting National Cancer Database. Subjects and Methods Patients diagnosed with laryngeal squamous cell carcinoma who were treated with curative intent were identified in the National Cancer Database. Multivariate analysis was utilized to determine factors correlated with overall survival in the HPV-negative and HPV-positive cohorts. Unadjusted and propensity score-weighted Kaplan-Meier estimation was used to determine overall survival of HPV-negative and HPV-positive patients across AJCC stage groupings. Results We identified 3238 patients with laryngeal squamous cell carcinoma, of which 2812 were HPV negative and 426 were HPV positive. Overall survival adjusted for age, sex, and comorbidity status confirmed significant differences among all consecutive stage groupings (I vs II, P < .001; II vs III, P < .05; III vs IVA, P < .001; IVA vs IVB, P < .05) in the HPV-negative cohort, whereas only stages IVAs and IVB ( P < .01) exhibited a significant difference in overall survival for HPV-positive patients. Conclusion The current AJCC staging system does not accurately distinguish risk of mortality for patients with HPV-positive disease. These data support the consideration of HPV status in estimating prognosis as well as clinical trial design and clinical decision making for patients with laryngeal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Background There is a paucity of data regarding head and neck squamous cell carcinomas (HNSCCs) and N3 nodal disease. Methods Retrospective analysis of patients with N3 HNSCC identified in the National Cancer Database (NCDB) was performed. Results We identified 4867 patients with N3 HNSCC treated with primary surgery or chemoradiotherapy (CRT). Propensity-adjusted median survival was 54.2 and 44.8 months for surgery and CRT, respectively ( P = .06). Oropharyngeal primary subsite demonstrated a survival advantage with surgery versus CRT with propensity-adjusted median survivals of 86.0 and 61.9 months, respectively ( P < .05). Conclusion Management of N3 HNSCC relies largely on CRT. Patients with N3 nodal disease with nonoropharyngeal primary tumors exhibit 5-year overall survival approaching 30% independent of initial treatment modality. Patients with oropharyngeal primaries exhibit improved outcomes with surgery largely influenced by the human papillomavirus (HPV)-negative subset. These data represent the most comprehensive analysis of N3 HNSCC outcomes and serves as a foundation for future research and clinical management. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): To examine the association between CD44 and c-MET expression in relation to p16 and EGFR in patients with head and neck squamous cell carcinoma (HNSCC).Materials/methods: Immunohistochemical staining of CD44, p16, EGFR, and c-MET was performed on 105 locally advanced HNSCC patients treated with chemoradiation. CD44 expression was correlated with c-MET, EGFR, and p16, locoregional control (LRC), distant metastases (DM), disease-free survival (DFS) and overall survival (OS).Results: High CD44 expression was present in 33% of patients and was associated with non-oropharynx primaries (P < 0.001), high c-MET expression (P < 0.001), p16-negative (P < 0.001) and EGFR-positive tumors (P < 0.001). Fifty-seven percent of CD44 high expressing tumors had high c-MET expression compared to 21% of CD44 low expressing tumors (P < 0.001). High CD44 expression predicted for worse LRC (HR: 2.44; 95% CI: 1.16-5.13; P = 0.018), DFS (HR: 2.61; 95% CI: 1.46-4.67; P = 0.001), and OS (HR: 2.52; 95% CI: 1.30-4.92; P = 0.007) but not DM (P = 0.57) on univariate analysis. Patients with both high CD44 and c-MET expression had a poor prognosis with a 2-year DFS of 30% compared to 70% in the rest of the cohort (P = 0.003). On multivariable analysis, after adjusting for site, T-stage, smoking history, and EGFR status, high c-MET (P = 0.039) and negative p16 status (P = 0.034) predicted for worse DFS, while high CD44 expression did not (P = 0.43).Conclusions: High CD44 expression is associated with high c-MET expression, p16-negative tumors, and EGFR-positive tumors. The combination of these markers predicts for poor prognosis in HNSCC patients treated with chemoradiation. [ABSTRACT FROM AUTHOR]

ABSTRACT Background We compared dependence rates, complications, toxicities, and costs associated with prophylactic versus reactive percutaneous endoscopic gastrostomy (PEG) tube placement. Methods One hundred ninety-three patients with locally advanced head and neck squamous cell carcinoma treated with concurrent chemoradiotherapy were retrospectively reviewed. Results The 1-year and 2-year actuarial PEG tube dependence rate of the entire cohort was 24% and 13%, respectively. There was no difference in the PEG tube dependence rates between those placed prophylactically versus reactively. Patients who received a PEG tube reactively had a significantly higher stricture rate ( p = .03) and aspiration rate ( p < .001) compared to the prophylactic group. There were significantly fewer hospitalizations in the prophylactic group compared to the reactive group ( p = .003). When accounting for both PEG placement and hospitalizations, the prophylactic approach was found to be more cost effective. Conclusion PEG tubes placed prophylactically were associated with lower rates of strictures, aspirations, hospitalizations, and costs compared to those placed reactively. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1155-1161, 2014 [ABSTRACT FROM AUTHOR]