Supplementary Figure 1 - PDF file 143K, ROC curves corresponding to the use of gene signatures, clinical exam and a combination of these. A: Risk Classification; B: EDNRB; C: DCC; D: EDNRB and DCC; E: EDNRB and Risk Classification; F: DCC and Risk Classification; G: EDNRB, DCC and Risk Classification

Supplementary Data - PDF file 79K, Supplementary data revised, figure added

Supplementary Table 1 - PDF file 90K, Predictive accuracy of risk classification and markers (n=161)

Supplementary Table 2 - PDF file 42K, Association between risk assessment and genes hypermethylation status

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and minorities have the worst survival. However, the molecular mechanisms underlying survival disparities have not been elucidated.

BACKGROUND:Hypermetabolism of thyroid nodules on (18)F-fluorodeoxyglucose positron emission tomography (PET) is associated with a higher prevalence of malignancy. However, the definition of hypermetabolism and its impact on cytological interpretation are unclear.METHODS:Medical records of all patients with thyroid nodules who had undergone cytological evaluation at the Moffitt Cancer Center between October 2008 and May 2014 were retrospectively reviewed. Those with a PET scan performed within one year of the cytology composed the study group, and the rest were used as controls. The distribution of the cytological categories, percentage of resection, and prevalence of malignancy among each Bethesda category was compared between both groups.RESULTS:Fifteen percent (436) of all thyroid nodules with cytological evaluation were in the study group. Maximum standardized uptake values (SUVmax) were directly associated with the probability of having a malignant or a follicular neoplasm cytological diagnosis; and inversely associated with the probability of having a benign cytological diagnosis. However, the prevalence of cancer within each Bethesda category was not associated with SUVmax values. It was found that the prevalence of malignant cytology increased to >5% with SUVmax values ≥2.5. SUVmax values were significantly higher in malignant than in benign nodules on histology (mean values 10.8 vs. 5) but with significant overlap between both groups for either the whole cohort or nodules with indeterminate cytology only limiting its use for differential diagnosis.CONCLUSIONS:The prevalence of malignancy in thyroid nodules with a SUVmax <2.5 is similar to the general population, and management should not be modified in those patients. The increased prevalence of malignancy among hypermetabolic thyroid nodules (SUVmax ≥2.5) is well characterized by cytology and does not impact the interpretation of cytological categories. Therefore, SUVmax value does not add relevant information once cytology is available.

OBJECTIVE:There is no definitive consensus on the impact of preoperative embolization on carotid body paraganglioma management. The purpose of this study was to assess the effects of preoperative embolization on carotid body paraganglioma excision. DATA SOURCES:A systematic search was conducted without limits, and it included studies published on or before July 2013 from PubMed, CINAHL, Web of Knowledge, and the Cochrane Library. Relevant synonyms for the search terms "paraganglioma,""carotid body tumor," and "embolization" were applied. REVIEW METHODS:Studies evaluating patients undergoing surgical intervention with embolization for carotid body tumors were included. Two reviewers independently assessed the titles and abstracts for inclusion and extracted the data. The guidelines set forth by the Cochrane Collaboration were followed in the process of data extraction. Data were pooled with a fixed effects model, and standardized mean difference (SMD) and 95% confidence intervals (95% CIs) are reported. RESULTS:A total of 22 studies (15 nonrandomized studies with a comparator, 7 single-arm studies) were included, enrolling 578 patients with 607 tumors. Patients undergoing preoperative embolization had significantly less estimated blood loss compared with those of surgical excision only (12 studies; 295 tumors; SMD: -0.52; 95% CI: -0.77, -0.28). Patients undergoing preoperative embolization had less operative time compared with that of surgical excision only (6 studies; 174 tumors; SMD: -0.46; 95% CI: -0.77, -0.14). CONCLUSION:Surgical excision with preoperative embolization appears to decrease estimated blood loss and operative time when compared with that without preoperative embolization for carotid body paragangliomas.

ObjectiveThere is no definitive consensus on the impact of preoperative embolization on carotid body paraganglioma management. The purpose of this study was to assess the effects of preoperative embolization on carotid body paraganglioma excision.Data SourcesA systematic search was conducted without limits, and it included studies published on or before July 2013 from PubMed, CINAHL, Web of Knowledge, and the Cochrane Library. Relevant synonyms for the search terms “paraganglioma,”“carotid body tumor,” and “embolization” were applied.Review MethodsStudies evaluating patients undergoing surgical intervention with embolization for carotid body tumors were included. Two reviewers independently assessed the titles and abstracts for inclusion and extracted the data. The guidelines set forth by the Cochrane Collaboration were followed in the process of data extraction. Data were pooled with a fixed effects model, and standardized mean difference (SMD) and 95% confidence intervals (95% CIs) are reported.ResultsA total of 22 studies (15 nonrandomized studies with a comparator, 7 single‐arm studies) were included, enrolling 578 patients with 607 tumors. Patients undergoing preoperative embolization had significantly less estimated blood loss compared with those of surgical excision only (12 studies; 295 tumors; SMD: –0.52; 95% CI: –0.77, –0.28). Patients undergoing preoperative embolization had less operative time compared with that of surgical excision only (6 studies; 174 tumors; SMD: –0.46; 95% CI: –0.77, –0.14).ConclusionSurgical excision with preoperative embolization appears to decrease estimated blood loss and operative time when compared with that without preoperative embolization for carotid body paragangliomas.

These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (H&N) Cancers. These Insights describe the different types of particle therapy that may be used to treat H&N cancers, in contrast to traditional radiation therapy (RT) with photons (x-ray). Research is ongoing regarding the different types of particle therapy, including protons and carbon ions, with the goals of reducing the long-term side effects from RT and improving the therapeutic index. For the 2015 update, the NCCN H&N Cancers Panel agreed to delete recommendations for neutron therapy for salivary gland cancers, because of its limited availability, which has decreased over the past 2 decades; the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages. (J Natl Compr Canc Netw 2015;13:847–856) Head and Neck Cancers, Version 1.2015 848 NCCN Guidelines Insights C E © JNCCN—Journal of the National Comprehensive Cancer Network | Volume 13 Number 7 | July 2015 Disclosure of Relevant Financial Relationships Editor: Kerrin M. Green, MA, Assistant Managing Editor, JNCCN—Journal of the National Comprehensive Cancer Network, has disclosed that she has no relevant financial relationships. CE Planners: Deborah J. Moonan, RN, BSN, Director, Continuing Education, NCCN, has disclosed that she has no relevant financial relationships. Ann Gianola, MA, Manager, Continuing Education Accreditation & Program Operations, NCCN, has disclosed that she has no relevant financial relationships. Kristina M. Gregory, RN, MSN, OCN, Vice President, Clinical Information Operations, NCCN, has disclosed that she has no relevant financial relationships. Rashmi Kumar, PhD, Senior Manager, Clinical Content, NCCN, has disclosed that she has no relevant financial relationships. Individuals Who Provided Content Development and/or Authorship Assistance: Sharon Spencer, MD, Panel Vice-Chair, has disclosed that she has no relevant financial relationships. Robert L. Foote, MD, Panel Member, has disclosed that is a chapter author and receives royalties from UpToDate. Sue S. Yom, MD, PhD, Panel Member, has disclosed that she receives clinical trial research support from Genentech Inc. Nicole McMillian, MS, Guidelines Coordinator, NCCN, has disclosed that she has no relevant financial relationships. Miranda Hughes, PhD, Oncology Scientist/Senior Medical Writer, NCCN, has disclosed that she has no relevant financial relationships. Supported by an educational grant from Eisai; a contribution from Exelixis Inc.; educational grants from Bristol-Myers Squibb, Genentech BioOncology, Merck, Novartis Oncology, Novocure; and by an independent educational grant from Boehringer Ingelheim Pharmaceuticals, Inc. NCCN: Continuing Education Accreditation Statement This activity is designated to meet the educational needs of physicians, nurses, and pharmacists involved in the management of patients with cancer. There is no fee for this article. The National Comprehensive Cancer Network (NCCN) is accredited by the ACCME to provide continuing medical education for physicians. NCCN designates this journal-based CE activity for a maximum of 1.0 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. NCCN is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center`s Commission on Accreditation. NCCN designates this educational activity for a maximum of 1.0 contact hour. Accreditation as a provider refers to recognition of educational activities only; accredited status does not imply endorsement by NCCN or ANCC of any commercial products discussed/displayed in conjunction with the educational activity. Kristina M. Gregory, RN, MSN, OCN, is our nurse planner for this educational activity. National Comprehensive Cancer Network is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. NCCN designates this continuing education activity for 1.0 contact hour(s) (0.1 CEUs) of continuing education credit in states that recognize ACPE accredited providers. This is a knowledge-based activity. UAN: 0836-0000-15-008-H01P All clinicians completing this activity will be issued a certificate of participation. To participate in this journal CE activity: 1) review the learning objectives and author disclosures; 2) study the education content; 3) take the posttest with a 66% minimum passing score and complete the evaluation at http://education.nccn.org/node/70211; and 4) view/print certificate. Release date: July 9, 2015; Expiration date: July 9, 2016 Learning Objectives: Upon completion of this activity, participants will be able to: • Integrate into professional practice the updates to the NCCN Guidelines for Head and Neck Cancers • Describe the rationale behind the decision-making process for developing the NCCN Guidelines for Head and Neck Cancers

Head and neck squamous cell carcinoma (HNSCC) is a devastating illness with racial/ethnic disparities in survival. Using a retrospective study design, we evaluated 210 somatic mutation sties of 10 cancer genes (i.e., CDKN2A, EGFR, FGFR3, HRAS, KRAS, MET, NOTCH1, PIK3CA, STK11, and TP53) in 214 HNSCC patients: 98 Non-Hispanic Whites (NHW; 46%), 72 Hispanic Whites (HW; 34%), and 44 African Americans (AA; 20%). HW and AA had significantly higher mutation rates for EGFR, HRAS, KRAS, and TP53 compared to that in NHW. Significantly higher proportions of HW (30%) and AA (18%) had at least 3 mutations compared to that in NHW (p Citation Format: Omar L. Nelson, Evan S. Wu, Jong Y. Park, Joseph Zeitouni, Carmen R. Gomez, Isildinha M. Reis, Wei Zhao, Eunkyung Lee, Hui-Yi Lin, Elizabeth J. Franzman, Jason Savell, Thomas V. McCaffrey, W. Jarrard Goodwin, Jennifer J. Hu. Actionable somatic mutations in head and neck cancer prognosis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3876. doi:10.1158/1538-7445.AM2015-3876

혈관성 평활근종은 혈관 및 평활근으로 구성되는 양성 종 양으로 전체 양성 연조직 종양의 4.4%를 차지한다. 평활근이 존재하는 곳에서는 어디서든 발생할 수 있으나, 주로 하지 (59%)와 상지(15%)의 피부에서 생기는 경우가 많으며 두경부 영역에서 발생하는 경우는 5~15%에 불과하다. 그중에서도 비강이나 부비동은 혈관성 평활근종이 매우 드물게 발생하 는 것으로 알려져 있으며, 이는 혈관 외에는 비강 내에 평활근 조직이 거의 존재하지 않기 때문으로 여겨진다. 비강이나 부비동에서 발생하는 혈관성 평활근종에 대해 현 재까지 여러 연구들이 보고되었으나, 매우 드문 발병률로 인해 대부분의 연구들은 1~2예의 증례 보고에 불과하였다. 현재 까지 보고된 연구 중에서 가장 대규모의 연구는 Hachisuga 등이 부위에 상관없이 체내에 발생한 562예의 혈관성 평활 근종에 대해 보고한 것으로, 그중 6예가 비강에서 발생한 것 이었다. 또한 Wang 등은 두경부 영역에 발생한 21예의 혈관 성 평활근종을 보고하였으며, 이 중에서는 3예가 비강에서 발 생한 경우였다. 국내에서는 Yoon 등이 비강에서 발생한 5예 를 포함한 두경부 영역의 혈관성 평활근종 12예를 보고한 것 이 가장 큰 연구였다. 따라서 현재까지 비강과 부비동에 발생한 혈관성 평활근종을 대상으로 그 임상 양상을 정리하여 보고 한 연구는 없었다. 저자들은 비중격에서 발생한 혈관성 평활근종 1예를 비중 격 점막 박리를 통해 정상 조직과 점막의 손상 없이 절제하여 이를 보고하며, 또한 현재까지 보고된 증례들에 대한 문헌 고 찰을 통해 비강과 부비동에 발생한 혈관성 평활근종의 임상 양상을 정리하여 함께 보고하는 바이다.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers focuses on glottic laryngeal cancer, which is the most common type of laryngeal cancer and has an excellent cure rate. The lymphatic drainage of the glottis is sparse, and early stage primaries rarely spread to regional nodes. Because hoarseness is an early symptom, most glottic laryngeal cancer is early stage at diagnosis. Updates to these guidelines for 2014 include revisions to "Principles of Radiation Therapy" for each site and "Principles of Surgery," and the addition of a new section on "Principles of Dental Evaluation and Management."

Objectives/HypothesisChondrosarcoma is a rare malignancy of the head and neck with fewer than 600 cases described in the literature. Treatment typically consists of conservation surgery with preservation of airway and preoperative voice quality. We describe five patients treated with a conservative transcervical approach utilizing the operating microscope for submucosal microdissection.Study DesignRetrospective case series at a National Cancer Institute–designated comprehensive cancer center.MethodsA retrospective case series from February 2004 to February 2011 was performed for all consecutive patients with laryngeal chondrosarcoma treated by the senior author with transcervical submucosal microdissection utilizing the operating microscope.ResultsFive patients with laryngeal chondrosarcoma were treated between February 2004 and February 2011. There were three male and two female patients who ranged in age from 56 to 87 years (mean, 72 years) at presentation. All five tumors were located at the level of the cricoid cartilage. Hoarseness was the most common presenting symptom (60%). Eighty percent of patients had limited vocal cord mobility. No patients required neck dissection or received radiation or chemotherapy. None of the five patients had recurrence after this approach.ConclusionsLaryngeal chondrosarcoma is a rare tumor. Conservative surgical resection remains the mainstay of treatment. The use of an operating microscope can aid in successful resection of laryngeal chondrosarcoma while preserving laryngeal mucosa and function.Level of Evidence4.

Abstract Purpose: Promoter hypermethylation has been recently proposed as a means for head and neck squamous cell carcinoma (HNSCC) detection in salivary rinses. In a prospective study of a high-risk population, we showed that endothelin receptor type B (EDNRB) promoter methylation in salivary rinses is a useful biomarker for oral cancer and premalignancy. Experimental Design: Using that cohort, we evaluated EDNRB methylation status and 8 additional genes. Clinical risk assessment by expert clinicians was conducted and compared with biomarker performance in the prediction of premalignant and malignant disease. Methylation status of 9 genes was analyzed in salivary rinses of 191 patients by quantitative methylation-specific PCR. Results: HOXA9, EDNRB, and deleted in colorectal cancer (DCC) methylation were associated (P = 0.012; P < 0.0001; P = 0.0005) with premalignant or malignant disease. On multivariable modeling, histological diagnosis was only independently associated with EDNRB (P = 0.0003) or DCC (P = 0.004) methylation. A subset of patients received clinical risk classification (CRC) by expert clinicians based on lesion examination. CRC, DCC, and EDNRB were associated with diagnosis of dysplasia/cancer on univariate (P = 0.008; P = 0.026; P = 0.046) and multivariate analysis (P = 0.012; P = 0.037; P = 0.047). CRC identified dysplasia/cancer with 56% of sensitivity and 66% of specificity with a similar area under curve [AUC; 0.61, 95% confidence interval (CI) = 0.60–0.81] when compared to EDNRB and DCC combined AUC (0.60, 95% CI = 0.51–0.69), sensitivity of 46% and specificity of 72%. A combination of EDNRB, DCC, and CRC was optimal AUC (0.67, 95% CI = 0.58–0.76). Conclusions: EDNRB and/or DCC methylation in salivary rinses compares well to examination by an expert clinician in CRC of oral lesions. These salivary biomarkers may be particularly useful in oral premalignancy and malignancy screening in clinical care settings in which expert clinicians are not available. Clin Cancer Res; 19(12); 3268–75. ©2013 AACR.

BACKGROUND:Over the past decade, intensity-modulated radiation therapy (IMRT) has gained widespread use in the treatment of head and neck cancer. METHODS:All patients with squamous cell carcinoma of the oropharynx treated with primary IMRT with or without chemotherapy over a 5-year period were reviewed. Outcomes and morbidity were analyzed and compared with previously published data. RESULTS:In all, 170 patients were included in the analysis. The 3-year local control, locoregional control, disease-free survival, and overall survival rates were 92%, 91%, 80%, and 87%, respectively. Feeding tubes were present in 55% of patients during treatment, but remained in only 1% 2 years following treatment. CONCLUSIONS:This study confirms that IMRT yields excellent treatment outcomes for oropharyngeal carcinoma. Although acute toxicity remains a problem, late toxicity rates are low and long-term feeding tube dependence is rare compared with conventional radiation therapy.

These NCCN Guidelines Insights focus on nutrition and supportive care for patients with head and neck cancers. This topic was a recent addition to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers. The NCCN Guidelines Insights focus on major updates to the NCCN Guidelines and discuss the new updates in greater detail. The complete version of the NCCN Guidelines for Head and Neck Cancers is available on the NCCN Web site (NCCN.org).