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PURPOSE The androgen receptor (AR) is expressed (+) in a subset of salivary gland cancers (SGCs). This phase II trial evaluated the efficacy of the antiandrogen enzalutamide in AR+ SGC. METHODS Patients with locally advanced/unresectable or metastatic AR+ SGCs were enrolled. Enzalutamide (160 mg) was given orally once daily. The primary end point was the best overall response rate per RECIST v1.1 within eight cycles. Confirmed responses in ≥ 5 of 41 patients would be considered promising. Secondary end points were progression-free survival, overall survival, and safety. RESULTS Forty-six patients were enrolled; 30 (65.2%) received prior systemic therapy, including 13 (28.3%) with AR-targeted drugs. Of seven (15.2%) partial responses (PRs), only two (4.3%) were confirmed per protocol and counted toward the primary end point. Twenty-four patients (52.2%) had stable disease; 15 (32.6%) had progression of disease as best response. Twenty-six patients (56.5%) experienced tumor regression in target lesions; 18 (39.1%) had partial response/stable disease ≥ 6 months. Tumor regressions were observed in female patients (5 of 6 [83.3%]) and those who received prior AR– (6 of 13 [46.2%]) or human epidermal growth factor receptor 2–targeted therapies (5 of 8 [62.5%]). Three patients remained on treatment at data cutoff (duration, 32.2-49.8 months). The median progression-free survival was 5.6 months (95% CI, 3.7 to 7.5); the median overall survival was 17.0 months (95% CI, 11.8 to 30.0). The most common adverse events were fatigue, hypertension, hot flashes, and weight loss. Total and free testosterone levels increased by a mean of 61.2% and 48.8%, respectively, after enzalutamide. CONCLUSION Enzalutamide demonstrated limited activity in AR+ SGC, failing to meet protocol-defined success in part because of a lack of response durability. Strategies to enhance the efficacy of antiandrogen therapy are needed.

PURPOSE To use a hybrid method, combining statistical profiling, machine learning (ML), and clinical evaluation to predict emergency department (ED) visits among patients with head and neck cancer undergoing radiotherapy. MATERIALS AND METHODS Patients with head and neck cancer treated with radiation therapy from 2015 to 2019 were identified using electronic health record data. Records from 60 days before 90 days after treatment were analyzed. Statistical profiling and ML were used to create a predictive model for ED visits during or after radiation therapy. A comprehensive set of variables were studied. Multiple ML models were developed including extreme gradient-boosted decision tree and generalized logistic regression with comparison of multiple predictive performance metrics. RESULTS Of the 1,355 patients studied, 13% had an ED visit during or after treatment. Our hybrid methodology enabled evidence-based winnowing of candidate features from 141 to 11 with clinically applicable, evidence-based thresholds. Extreme gradient boosting had the highest area under the curve (0.81 ± 0.06) with a sensitivity of 0.89 ± 0.10 and exceeded generalized logistic regression (area under the curve 0.64 ± 0.02). Significant predictors of ED visits during treatment included increasingly complex opioid use, number of prior ED visits, tumor volume, rate of change of blood urea nitrogen, total bilirubin, body mass index, and distance from hospital. CONCLUSION Our approach combining bootstrapped statistical profiling and ML importance analysis supported integration of clinician input to identify a distilled set of phenotypical characteristics for developing ML models predicting which patients undergoing head and neck cancer radiation therapy were at risk for ED visits.

Background: Sorafenib and lenvatinib are multikinase inhibitors (MKIs) approved for patients with radioactive iodine-refractory (RAI-R) differentiated thyroid cancer (DTC). There is no consensus on when to initiate MKI treatment. The objective of this study was to evaluate time to symptomatic progression (TTSP) in patients with RAI-R DTC for whom the decision to treat with an MKI was made at study entry. Methods: International, prospective, open-label, noninterventional cohort study (NCT02303444). Eligible patients had asymptomatic progressive RAI-R DTC, with ≥1 lesion ≥1 cm in diameter and life expectancy ≥6 months. The decision to treat with an MKI was at the treating physician's discretion. Primary endpoint was TTSP from study entry. Two cohorts were evaluated: patients for whom a decision to initiate an MKI was made at study entry (Cohort 1) and patients for whom there was a decision not to initiate an MKI at study entry (Cohort 2). Cohorts were compared descriptively. Results: The full analysis set (FAS) comprised 647 patients. The median duration of observation was 35.5 months (range

The current treatments for radioactive iodine (RAI) -refractory differentiated thyroid cancer (DTC) are evolving as cancer genomics are further understood. Multitargeted tyrosine kinase inhibitors are the first-line therapy for symptomatic or progressive disease; however, considerable adverse effects have spurred the development of targeted therapies for redifferentiation of iodine avidity and the treatment of RAI-refractory DTC. Next-generation sequencing allows for the use of tumor-targeted therapeutics, such as MEK1/2, BRAF, RET, and NTRK inhibitors. Immunotherapy is also under investigation as a therapeutic option for this disease.

In the randomized, phase 3 CheckMate 141 trial, nivolumab significantly improved overall survival (OS) versus investigator’s choice (IC) of chemotherapy at primary analysis among 361 patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) post-platinum therapy. Nivolumab versus IC as first-line treatment also improved OS among patients with R/M SCCHN who progressed on platinum therapy for locally advanced disease in the adjuvant or primary setting at 1-year follow-up. In the present long-term follow-up analysis of patients receiving first-line treatment, OS benefit with nivolumab (n = 50) versus IC (n = 26) was maintained (median: 7.7 months versus 3.3 months; hazard ratio: 0.56; 95% confidence interval, 0.34-0.94) at 2 years. No new safety signals were identified. In summary, this long-term 2-year analysis of CheckMate 141 supports the use of nivolumab as a first-line treatment for patients with platinum-refractory R/M SCCHN.

Highlights • Bioselection with induction chemotherapy in larynx cancer has good outcomes but has challenges. • CT imaging is complementary to surgeon assessment of response and may be incorporated. • Imaging features predict for surgeon assessment and laryngectomy-free survival. • Discordance between surgeon and imaging response may predict for worse outcomes., Background and purpose Bioselection with induction chemotherapy in larynx cancer is associated with excellent larynx preservation and disease-specific survival but requires visual inspection of the primary tumor. We retrospectively compare clinical and imaging response in bioselected patients to develop predictive models of surgeon-assessed response (SR), laryngectomy-free survival (LFS), and overall survival (OS) in bioselected patients. Materials and methods In a secondary analysis of patients on two single-institution bioselection trials, model building used a regularized regression model (elastic-net) and applied nested cross-validation. Logistic regression-based model was used to predict SR and Cox proportional hazard-based models were used to predict LFS and OS. Results In 115 patients with a median age of 57 years, most patients had supraglottic tumors (73.0%) and T3/T4 disease (94.8%). Definitive treatment was chemoradiation in 76.5% and laryngectomy in 23.5%. Change in primary tumor (OR = 5.78, p

Mutations in theWe enrolled 30 patients with R/M HNSCC in a single-arm, open-label phase II trial of tipifarnib for mOf the 22 patients with HNSCC with high VAF, 20 were evaluable for response at the time of data cutoff. Objective response rate for evaluable patients with high-VAF HNSCC was 55% (95% CI, 31.5 to 76.9). Median progression-free survival on tipifarnib was 5.6 months (95% CI, 3.6 to 16.4) versus 3.6 months (95% CI, 1.3 to 5.2) on last prior therapy. Median overall survival was 15.4 months (95% CI, 7.0 to 29.7). The most frequent treatment-emergent adverse events among the 30 patients with HNSCC were anemia (37%) and lymphopenia (13%).Tipifarnib demonstrated encouraging efficacy in patients with R/M HNSCC with

The American College of Radiology (ACR) Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. Here, we present the Appropriateness Criteria for cancers arising in the nasal cavity and paranasal sinuses (maxillary, sphenoid, and ethmoid sinuses). This includes clinical presentation, prognostic factors, principles of management, and treatment outcomes. Controversies regarding management of cervical lymph nodes are discussed. Rare and unusual nasal cavity cancers, such as esthesioneuroblastoma and sinonasal undifferentiated carcinomas, are included. © 2016 American College of Radiology. Head Neck, 2016 © 2016 Wiley Periodicals, Inc. Head Neck 39: 407-418, 2017.

Background There are no level I studies to guide treatment for resectable oropharyngeal squamous cell carcinoma (SCC). Treatment toxicities influence management recommendations. Ongoing investigations are examining deintensified treatments for human papillomavirus (HPV)-associated oropharyngeal SCC. Methods The Appropriateness Criteria panel, using modified Delphi methodology, produced a literature summary, an assessment of treatment recommendations, and cases to illustrate their use. Results A multidisciplinary team produces optimum results. Based on HPV status, smoking history, and staging, patients are divided into groups at low, intermediate, and high-risk of death. In the future, treatment recommendations may be influenced by HPV status, which has changed the epidemiology of oropharyngeal SCC. Conclusion T1 to T2N0M0 resectable oropharyngeal SCC can be treated with surgery or radiation without chemotherapy. Patients with T1-2N1-2aM0 disease can receive radiation, chemoradiation, or transoral surgery with neck dissection and appropriate adjuvant therapy. Patients with T1-2N2b-3M0 disease should receive chemoradiation or transoral surgery with neck dissection and appropriate adjuvant therapy. Concurrent chemoradiation is preferred for T3 to T4 disease. © 2016 American College of Radiology. Head Neck, 2016

Background Nasopharyngeal carcinoma (NPC) presents mostly with locally advanced disease and is treated with multimodal therapy; however, consensus is lacking for different clinical scenarios. Methods The American College of Radiology (ACR) Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Results The ACR Expert Panel on Radiation Oncology – Head and Neck Cancer developed consensus recommendations for guiding management of nasopharyngeal carcinoma. Conclusion Multidisciplinary evaluation is essential to guiding the optimal use of surgery, radiation, and systemic therapy in this disease. © 2015 American College of Radiology Head Neck, 2015

Background Aggressive nonmelanomatous skin cancer (NMSC) of the head and neck presents an increasingly common therapeutic challenge for which prospective clinical trials are lacking. Methods The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Results The American College of Radiology Expert Panel on Radiation Oncology – Head and Neck Cancer developed consensus recommendations for guiding management of aggressive NMSC. Conclusion Multidisciplinary assessment is vital to guiding the ideal use of surgery, radiation, and systemic therapy in this disease. © 2016 Wiley Periodicals, Inc. Head Neck 38: 175–182, 2016

Summary The ACR Head and Neck Cancer Appropriateness Criteria Committee reviewed relevant medical literature to provide guidance for those managing patients with thyroid carcinoma. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Thyroid cancer is the most common endocrine malignancy in the United States, most often presenting as a localized palpable nodule. Surgery is the mainstay of treatment for WDTC, with most patients undergoing complete resection of their disease having good outcomes. Following surgery thyroxine supplementation should begin to suppress TSH, which unchecked can stimulate residual disease and/or metastatic progression, Adjuvant treatment with radioactive iodine (RAI) using iodine-131 ( 131 I) is frequently used for diagnostic and therapeutic purposes. The use of EBRT for thyroid cancer has not been tested in well-designed, randomized, controlled trials and should, therefore, be considered on a case-by-case basis. Chemotherapy plays a minimal role in the management of WDTC. Novel biologic agents, such as systemic therapy options, are being actively investigated, and patients with metastatic thyroid cancer that is not iodine avid should be encouraged to enroll in clinical trials exploring novel systemic agents.

Background Controversy surrounds the appropriate therapy for T1 glottic cancer. Both transoral endolaryngeal resection and radiation offer excellent local control and voice quality; some lesions are best addressed with resection and others with radiation. Methods The American College of Radiology (ACR) Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed by a multidisciplinary expert panel. The guideline development includes an analysis of current literature from peer reviewed journals and the well-established “modified Delphi” consensus methodology to rate the appropriateness of treatment. Where evidence is not definitive, expert opinion informed recommendations. Results The ACR Expert Panel on Radiation Oncology – Head and Neck Cancer developed consensus recommendations for treatment of T1 glottic cancer. Treatment planning is complex and decisions nuanced. Conclusion Best treatment for a particular cancer cannot be defined without consideration of the lesion's location, extent, depth of invasion, and quality of surgical exposure during direct laryngoscopy. © 2013 American College of Radiology. Head & Neck © 2013 Wiley Periodicals, Inc. Head Neck 36: 3–8, 2014

The American College of Radiology (ACR) Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. Here, we present the Appropriateness Criteria for cancers arising in the nasal cavity and paranasal sinuses (maxillary, sphenoid, and ethmoid sinuses). This includes clinical presentation, prognostic factors, principles of management, and treatment outcomes. Controversies regarding management of cervical lymph nodes are discussed. Rare and unusual nasal cavity cancers, such as esthesioneuroblastoma and sinonasal undifferentiated carcinomas, are included. © 2016 American College of Radiology. Head Neck, 2016 © 2016 Wiley Periodicals, Inc. Head Neck 39: 407-418, 2017.

There are no level I studies to guide treatment for resectable oropharyngeal squamous cell carcinoma (SCC). Treatment toxicities influence management recommendations. Ongoing investigations are examining deintensified treatments for human papillomavirus (HPV)-associated oropharyngeal SCC.The Appropriateness Criteria panel, using modified Delphi methodology, produced a literature summary, an assessment of treatment recommendations, and cases to illustrate their use.A multidisciplinary team produces optimum results. Based on HPV status, smoking history, and staging, patients are divided into groups at low, intermediate, and high-risk of death. In the future, treatment recommendations may be influenced by HPV status, which has changed the epidemiology of oropharyngeal SCC.T1 to T2N0M0 resectable oropharyngeal SCC can be treated with surgery or radiation without chemotherapy. Patients with T1-2N1-2aM0 disease can receive radiation, chemoradiation, or transoral surgery with neck dissection and appropriate adjuvant therapy. Patients with T1-2N2b-3M0 disease should receive chemoradiation or transoral surgery with neck dissection and appropriate adjuvant therapy. Concurrent chemoradiation is preferred for T3 to T4 disease. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1299-1309, 2016.

Nasopharyngeal carcinoma (NPC) presents mostly with locally advanced disease and is treated with multimodal therapy; however, consensus is lacking for different clinical scenarios.The American College of Radiology (ACR) Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.The ACR Expert Panel on Radiation Oncology - Head and Neck Cancer developed consensus recommendations for guiding management of nasopharyngeal carcinoma.Multidisciplinary evaluation is essential to guiding the optimal use of surgery, radiation, and systemic therapy in this disease. © 2015 Wiley Periodicals, Inc. Head Neck 38: 979-986, 2016.

Aggressive nonmelanomatous skin cancer (NMSC) of the head and neck presents an increasingly common therapeutic challenge for which prospective clinical trials are lacking.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.The American College of Radiology Expert Panel on Radiation Oncology - Head and Neck Cancer developed consensus recommendations for guiding management of aggressive NMSC.Multidisciplinary assessment is vital to guiding the ideal use of surgery, radiation, and systemic therapy in this disease.

Tumor regression after induction chemotherapy (ICT) identifies laryngeal cancers that are responsive to chemoradiation. Patient immune parameters have recently been associated with response to chemotherapy and may identify responding patients. A retrospective analysis was performed to determine if pretreatment, circulating T lymphocyte levels predicted ICT response in patients with advanced laryngeal cancer.Pretreatment, circulating T lymphocyte subpopulations were correlated with response to therapy and survival. Results were compared with similar data from an identical phase II trial involving patients with oropharyngeal cancer.An increased percentage of CD4+ cells predicted response to ICT and suggested improved survival in patients with laryngeal, but not oropharyngeal, cancer. In the combined group of patients, increased CD4 levels predicted response to ICT.These findings demonstrate the potential importance of the immune system in chemotherapy response and clinical outcome. Differences in findings between patients with advanced laryngeal and oropharyngeal cancer may reflect different cellular immunity function in the patients with human papillomavirus (HPV)-16+ oropharyngeal cancer.

Because anaplastic thyroid cancer is a rare malignancy with a high mortality rate, the benefit of multimodality treatment was evaluated.Overall survival was determined in the 2742 patients captured by the National Cancer Database who were diagnosed with anaplastic thyroid cancer between 1998 and 2008. Kaplan-Meier analysis and then Cox proportional hazard regression was performed, controlling for patient characteristics and treatment.Only older age (adjusted hazard ratio [AHR] for ≥ 85 years = 3.43, 95% confidence interval [CI] = 2.34-5.03; for 75-84 years, AHR = 2.85, 95% CI = 1.97-4.11; for 65-74 years, AHR = 2.20, 95% CI = 1.53-3.15; for 45-64 years, AHR = 2.08, 95% CI = 1.47-2.95) and omission of treatment were associated with greater mortality (omission of surgery: AHR = 1.79, 95% CI = 1.61-1.99; omission of radiation therapy: AHR = 1.56; 95% CI = 1.41-1.73; and omission of chemotherapy: AHR = 1.28, 95% CI = 1.15-1.43). In subgroup analysis of patients with American Joint Committee on Cancer stage IVA, IVB, and IVC anaplastic thyroid cancer, combination therapy with surgery, radiation, and chemotherapy was associated a difference in median survival of months.Multimodality management of anaplastic thyroid cancer results in a marginal treatment benefit. The poor overall survival of all anaplastic thyroid cancer patients, regardless of treatment, emphasizes the need for informed patients whose preferences are incorporated into treatment decision-making.

Little is known about the determinants of postradiation neck spasms in patients with head and neck cancer.Patients with head and neck cancer treated with radiation therapy (RT) from 2004 to 2010 who experienced neck spasms werereviewed. Radiation doses were generated for their sternocleidomastoid (SCM) muscles bilaterally. Unaffected SCMs were used as controls.Thirty-four patients reported neck spasms. Thirty had received definitive chemoradiation, and 4 had RT alone. Seven also had an ipsilateral neck dissection. Median time to onset was 23 months (range, 6-67 months). There were significantly higher radiation doses to the affected SCMs with a median of the mean dose to the affected and unaffected SCM of 62.3 Gy (range, 29-71 Gy) and 53.7 Gy (range, 27-65 Gy), respectively (p.0001). Other dosimetric variables were also statistically significant but were highly correlated with the mean SCM dose. Neck dissection did not affect our results.Neck spasms after chemotherapy intensity-modulated radiation therapy (IMRT) shows a strong dose-response relationship.

Controversy surrounds the appropriate therapy for T1 glottic cancer. Both transoral endolaryngeal resection and radiation offer excellent local control and voice quality; some lesions are best addressed with resection and others with radiation.The American College of Radiology (ACR) Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed by a multidisciplinary expert panel. The guideline development includes an analysis of current literature from peer reviewed journals and the well-established "modified Delphi" consensus methodology to rate the appropriateness of treatment. Where evidence is not definitive, expert opinion informed recommendations.The ACR Expert Panel on Radiation Oncology - Head and Neck Cancer developed consensus recommendations for treatment of T1 glottic cancer. Treatment planning is complex and decisions nuanced.Best treatment for a particular cancer cannot be defined without consideration of the lesion's location, extent, depth of invasion, and quality of surgical exposure during direct laryngoscopy.