2018-19 Section 7-Neoplastic and Inflammatory Diseases of the Head and Neck eBook

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Neoplastic and Inflammatory Diseases of the Head and Neck

Home Study Course

Hsc Home Study Course

Section 7 February 2019

© 2018 American Academy of Otolaryngology—Head and Neck Surgery Foundation The global leader in optimizing quality ear, nose, and throat patient care

THE HOME STUDY COURSE IN OTOLARYNGOLOGY -- HEAD AND NECK SURGERY

February 2019

SECTION 7

NEOPLASTIC AND INFLAMMATORY DISEASES OF THE HEAD AND NECK

SECTION FACULTY:

Ted H. Leem, MD, MS** Bradley A. Schiff, MD** Salvatore M. Caruana, MD Zhen Gooi, MD Gina D. Jefferson, MD Matthew O. Old, MD Mike Yao, MD

American Academy of Otolaryngology - Head and Neck Surgery Foundation

Section 7 exam deadline: March 11, 2019 Expiration Date: August 6, 2019; CME credit not available after that date

Introduction The Home Study Course is designed to provide relevant and timely clinical information for physicians in training and current practitioners in otolaryngology - head and neck surgery. The course, spanning four sections, allows participants the opportunity to explore current and cutting- edge perspectives within each of the core specialty areas of otolaryngology. The Selected Recent Material represents primary fundamentals, evidence-based research, and state of the art technologies in neoplastic and inflammatory diseases of the head and neck. The scientific literature included in this activity forms the basis of the assessment examination. The number and length of articles selected are limited by editorial production schedules and copyright permission issues and should not be considered an exhaustive compilation of knowledge on Neoplastic and Inflammatory Diseases of the Head and Neck. The Additional Reference Material is provided as an educational supplement to guide individual learning. This material is not included in the course examination and reprints are not provided. Needs Assessment AAO-HNSF’s education activities are designed to improve healthcare provider competence through lifelong learning. The Foundation focuses its education activities on the needs of providers within the specialized scope of practice of otolaryngologists. Emphasis is placed on practice gaps and education needs identified within eight subspecialties. The Home Study Course selects content that addresses these gaps and needs within all subspecialties. Target Audience The primary audience for this activity is physicians and physicians-in-training who specialize in otolaryngology-head and neck surgery. Outcomes Objectives The participant who has successfully completed this section should be able to: 1. Explain the extent the effect the number of positive lymph nodes has on patients with parotid malignancies. 2. Describe factors that influence disease free survival in patients with submandibular gland salivary cancer. 3. Discuss the current clinical trials available for patients with head and neck melanoma. 4. Define the current uses and outcomes of de-intensified treatment for patients with oropharyngeal squamous cell carcinoma 5. Describe the rational for and the effects of the recent change in nomenclature from encapsulated follicular variant of papillary thyroid carcinoma to neoplasm with papillary-like nuclear features. 6. Summarize the recent changes in the staging of Head and Neck cancer patients found in the \AJCC 8th edition. 7. Review common predictors of complications for Head and Neck Cancer patients treated with free flap reconstruction. 8. Develop a treatment strategy for patients with deep neck space abscesses. 9. Discuss the outcomes of clinical trials using immunotherapeutic agents for recurrent and metastatic head and neck cancer.

Medium Used The Home Study Course is available in electronic or print format. The activity includes a review of outcomes objectives, selected scientific literature, and an online self-assessment examination. Method of Physician Participation in the Learning Process The physician learner will read the selected scientific literature, reflect on what they have read, and complete the self-assessment exam. After completing this section, participants should have a greater understanding of Neoplastic and Inflammatory Diseases of the Head and Neck as they affect the head and neck area, as well as useful information for clinical application. Accreditation Statement The American Academy of Otolaryngology—Head and Neck Surgery Foundation (AAO-HNSF) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Credit Designation The AAO-HNSF designates this enduring material for 40.0 AMA PRA Category 1 Credit(s) ™. Physicians should claim credit commensurate with the extent of their participation in the activity. ALL PARTICIPANTS must achieve a post-test score of 70% or higher for a passing completion to be recorded and a transcript to be produced. Residents’ results will be provided to the Training Program Director. PHYSICIANS ONLY : In order to receive Credit for this activity a post-test score of 70% or higher is required . Two retest opportunity will be automatically be available if a minimum of 70% is not achieved. Disclosure The American Academy of Otolaryngology Head and Neck Surgery/Foundation (AAO-HNS/F) supports fair and unbiased participation of our volunteers in Academy/Foundation activities. All individuals who may be in a position to control an activity’s content must disclose all relevant financial relationships or disclose that no relevant financial relationships exist. All relevant financial relationships with commercial interests 1 that directly impact and/or might conflict with Academy/Foundation activities must be disclosed. Any real or potential conflicts of interest 2 must be identified, managed, and disclosed to the learners. In addition, disclosure must be made of presentations on drugs or devices or uses of drugs or devices that have not been approved by the Food and Drug Administration. This policy is intended to openly identify any potential conflict so that participants in an activity are able to form their own judgments about the presentation. [1] A “Commercial interest” is any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients. 2 “Conflict of interest” is defined as any real or potential situation that has competing professional or personal interests that would make it difficult to be unbiased. Conflicts of interest occur when an individual has an opportunity to affect education content about products or services of a commercial interest with which they have a financial relationship. A conflict of interest depends on the situation and not on the character of the individual. Estimated time to complete this activity: 40.0 hours

February 2019 Section 7 NEOPLASTIC AND INFLAMMATORY DISEASES OF THE HEAD AND NECK FACULTY

** Co-Chairs: Ted H. Leem, MD, MS, FACS , Southern California Permanente Medical Group Downey, California Disclosure: No relationships to disclose Bradley A. Schiff, MD , Associate Professor Department of Otorhinolaryngology-Head and Neck Surgery, Director, Division of Head and Neck Surgery, Montefiore Medical Center, Bronx, New York Disclosure: No relationships to disclose. Faculty: Salvatore M. Caruana, MD, Associate Professor Department of Otolaryngology-Head and Neck Surgery, Columbia University College of Physicians and Surgeons; Director, Division of Head and Neck Surgery, New York, New York Disclosure: Salary: Olympus Zhen Gooi, MD, Assistant Professor, Section of Otolaryngology-Head and Neck Surgery Department of Surgery, University of Chicago, Chicago, Illinois Disclosure: Consultant: Ebix Gina D. Jefferson, MD, FACS, Associate Professor, Department of Otolaryngology and Communicative Sciences, University of Mississippi Medical Center; Vice Chair, Division of Head and Neck Oncologic and Microvascular Surgery, Jackson, Mississippi Disclosure: No relationships to disclose Matthew O. Old, MD, FACS, Head and Neck Division Director, Medical Director, Head and Neck Service Line, The James Cancer Hospital and Solove Research Institute, Wexner Medical Center at The Ohio State University, Department of Otolaryngology-Head and Neck Surgery Disclosure: No relationships to disclose Mike Yao, MD, Associate Professor, Department of Otolaryngology-Head and Neck Surgery, Icahn School of Medicine at Mount Sinai, New York, New York. Disclosure: No relationships to disclose.

Planner(s): Linda Lee, AAO─HNSF Education Senior Manager Stephanie Wilson, Stephanie Wilson Consulting, LLC; Production Manager David M. Cognetti, MD, chair, AAO-HNSF Head and Neck Surgery Education Committee Richard V. Smith, MD, chair, Education Steering Committee

No relationships to disclose No relationships to disclose

No relationships to disclose

Expert Witness: Various legal firms

This 2019 Home Study Course Section 7 does not include any discussion of drugs and devices that have not been approved by the United States Food and Drug Administration.

Disclaimer The information contained in this activity represents the views of those who created it and does not necessarily represent the official view or recommendations of the American Academy of Otolaryngology – Head and Neck Surgery Foundation.

March 11, 2019: Suggested section 7 Exam submission deadline; course closes August 6, 2019.

EVIDENCE-BASED MEDICINE The AAO-HNSF Education Advisory Committee approved the assignment of the appropriate level of evidence to support each clinical and/or scientific journal reference used to authenticate a continuing medical education activity. Noted at the end of each reference, the level of evidence is displayed in this format: [EBM Level 3] .

Oxford Centre for Evidence-based Medicine Levels of Evidence (May 2001) Level 1

Randomized 1 controlled trials 2 or a systematic review 3 (meta-analysis 4 ) of randomized controlled trials 5 . Prospective (cohort 6 or outcomes) study 7 with an internal control group or a systematic review of prospective, controlled trials. Retrospective (case-control 8 ) study 9 with an internal control group or a systematic review of retrospective, controlled trials. Case series 10 without an internal control group (retrospective reviews; uncontrolled cohort or outcome studies).

Level 2

Level 3

Level 4

Expert opinion without explicit critical appraisal, or recommendation based on physiology/bench research.

Level 5

Two additional ratings to be used for articles that do not fall into the above scale. Articles that are informational only can be rated N/A , and articles that are a review of an article can be rated as Review. All definitions adapted from Glossary of Terms, Evidence Based Emergency Medicine at New York Academy of Medicine at www.ebem.org . 1 A technique which gives every patient an equal chance of being assigned to any particular arm of a controlled clinical trial. 2 Any study which compares two groups by virtue of different therapies or exposures fulfills this definition. 3 A formal review of a focused clinical question based on a comprehensive search strategy and structure critical appraisal. 4 A review of a focused clinical question following rigorous methodological criteria and employing statistical techniques to combine data from independently performed studies on that question. 5 A controlled clinical trial in which the study groups are created through randomizations. 6 This design follows a group of patients, called a “cohort”, over time to determine general outcomes as well as outcomes of different subgroups. 7 Any study done forward in time. This is particularly important in studies on therapy, prognosis or harm, where retrospective studies make hidden biases very likely. 8 This might be considered a randomized controlled trial played backwards. People who get sick or have a bad outcome are identified and “matched” with people who did better. Then, the effects of the therapy or harmful

exposure which might have been administered at the start of the trial are evaluated. 9 Any study in which the outcomes have already occurred before the study has begun. 10 This includes single case reports and published case series.

OUTLINE

SECTION 7 FEBRUARY 2019

NEOPLASTIC AND INFLAMMATORY DISEASES OF THE HEAD AND NECK

I.

Salivary A. Extent of surgery/non-parotid tumors B. Chemotherapy, immunotherapy for salivary cancer

II.

Skin A. Melanoma

i. Changes in staging ii. MSLT1-2 B. Non melanoma skin cancer i. Merkel cell ii. When to do neck dissection for SCCA, role for sentinel node in SCCA

III.

Upper Aerodigestive Tract A. Oropharynx

i. Deintensification of therapy

IV.

Endocrine A. Reclassification of thyroid cancers B. Molecular testing

V.

Lymphatic A. New staging system

VI.

Complications A. Free flaps complication rates

VII.

Infectious Disease A. Abscess/infection treatment regarding medical vs surgical therapy

VIII. Nonsurgical A. Salvage therapy (immunotherapy, reirradiation, oligometastatic treatment, etc.)

TABLE OF CONTENTS Selected Recent Materials - Reproduced in this Study Guide

February 2019 SECTION 7 NEOPLASTIC AND INFLAMMATORY DISEASES OF THE HEAD AND NECK

ADDITIONAL REFERENCE MATERIAL…………………………………………. i - iii

I. Salivary A. Extent of surgery/non-parotid tumors

Aro K, Ho AS, Luu M, et al. Development of a novel salivary gland cancer lymph node staging system. Cancer . 2018; 124(15):3171-3180. EBM level 2+..............................................................................1-10

Summary : This article presents a retrospective observational study from the National Cancer Data Base of 4520 patients treated for salivary gland cancer with surgery and neck dissection with or without adjuvant radiation therapy. The study period was from 2004 to 2013. Univariate and multivariate analysis of multiple factors suggested that the absolute number of positive lymph nodes had a significant stepwise impact on patient outcomes and was more accurate in predicting prognosis than the AJCC 8th edition for lymph node metastasis. The number of lymph nodes involved exerted a greater influence on outcome than did extranodal extension and contralateral metastasis. Baddour HM Jr, Fedewa SA, Chen AY. Five- and 10-year cause-specific survival rates in carcinoma of the minor salivary gland. JAMA Otolaryngol Head Neck Surg . 2016; 142(1):67-73. EBM level 2+.................................................................................................................................................11-17 Summary : This is a retrospective, population-based study using the SEER database identifying 5334 patients with minor salivary gland cancers. Negative prognostic factors identified on multivariate analysis were primary site in the larynx or nasal cavity/sinuses and patient age > 75 years. Surgical intervention is demonstrated to have a positive prognostic influence on survival at 5 and 10 years. No association of survival with race, gender, or socioeconomic status was identified. By far, this is the largest study on minor salivary gland cancer in publication. Weaknesses include lack of tumor grade information and surgical intervention details. Lee RJ, Tan AP, Tong EL, et al. Epidemiology, prognostic factors, and treatment of malignant submandibular gland tumors: a population-based cohort analysis. JAMA Otolaryngol Head Neck Surg . 2015; 141(10):905-912. EBM level 2+...............................................................................................18-25 Summary : This is a retrospective, population-based, SEER-identified study of 2626 patients with primary malignancy of the submandibular salivary gland. Multivariate analysis revealed histology, stage at presentation, patient age, gender, tumor grade, and surgical resection to be predictive of overall and disease-specific survival. The study presents the largest data set on salivary tumors in publication.

Suárez C, Barnes L, Silver CE, et al. Cervical lymph node metastasis in adenoid cystic carcinoma of oral cavity and oropharynx: a collective international review. Auris Nasus Larynx . 2016; 43(5):477- 484. EBM level 4................................................................................................................................26-33 Summary : This article essentially presents a literature review and expert opinion written by some of the most notable investigators in the field of salivary gland cancers. The authors attempt to establish guidelines for neck dissection and management of adenoid cystic carcinoma of the oral cavity and oropharynx. B. Chemotherapy, immunotherapy for salivary cancer Amini A, Waxweiler TV, Brower JV, et al. Association of adjuvant chemoradiotherapy vs radiotherapy alone with survival in patients with resected major salivary gland carcinoma: data from the National Cancer Data Base. JAMA Otolaryngol Head Neck Surg . 2016; 142(11):1100-1110. EBM level 3.........................................................................................................................................34-44 Summary : This study is a retrospective analysis of 2210 patients with resected major salivary gland cancers from the National Cancer Data Base. The authors analyzed the difference in survival between patients who had chemoradiation versus radiation postoperatively. There was no survival advantage conferred with the addition of chemotherapy. Cheraghlou S, Kuo P, Mehra S, et al. Adjuvant therapy in major salivary gland cancers: analysis of 8580 patients in the National Cancer Database. Head Neck . 2018; 40(7):1343-1355. EBM level 3...................................................................................................................................................45-57 Summary : This study evaluated 8580 patients with salivary gland cancers in the National Cancer Data Base. Adjuvant radiation improved survival in salivary gland cancers with adverse features at any stage. However, the addition of chemotherapy did not improve outcomes in late-stage disease with adverse features. i. Changes in staging Eggermont AMM, Dummer R. The 2017 complete overhaul of adjuvant therapies for high-risk melanoma and its consequences for staging and management of melanoma patients. Eur J Cancer . 2017; 86:101-105. EBM level 1...................................................................................................58-62 Summary : This article reviews the major clinical trials for melanoma including studies of interferon, ipilimumab, nivolumab, pembrolizumab, and dabrafenib/trametinib. Nivolumab and the combination of dabrafenib/trametinib have shown the best results. Meta-analysis of the interferon studies shows that only patients with ulceration benefit from interferon. A. Melanoma

II. Skin

ii. MSLT 1-2 Faries MB, Han D, Reintgen M, et al. Lymph node metastasis in melanoma: a debate on the significance of nodal metastases, conditional survival analysis and clinical trials. Clin Exp Metastasis . 2018; 35(5-6):431-442. EBM level 1.......................................................................63-74 Summary : This article discusses the benefit of completion lymphadenectomy after sentinel lymph nodes are found to be positive. Two hypotheses about the spread of melanoma are discussed: incubator and marker hypotheses. The incubator hypothesis is that lymph nodes provide a haven for melanoma to grow and increase in metastatic potential. For the incubator hypothesis, lymphadenectomy provides benefit by removing this metastatic potential. The marker hypothesis is that the lymph nodes are a marker of clinically occult distant metastases, and lymphadenectomy in this setting provides no benefit. The recent trials concerning the benefits of completion lymphadenectomy are reviewed. Schmalbach CE, Bradford CR. Completion lymphadenectomy for sentinel node positive cutaneous head & neck melanoma. Laryngoscope Investig Otolaryngol . 2018; 3(1):43-48. EBM level 1............................................................................................................................................75-80 Summary : This article reviews the most recent clinical trials evaluating completion lymphadenectomy for positive sentinel node biopsy. Although no head and neck–specific prospective trials have been performed, the non-prospective head and neck melanoma studies are reviewed, and the applicability of findings of the prospective trials to patients with head and neck melanoma are analyzed. Han AY, Patel PB, Anderson M, et al. Adjuvant radiation therapy improves patient survival in early-stage Merkel cell carcinoma: a 15-year single-institution study. Laryngoscope . 2018; 128(8):1862-1866. EBM level 4...................................................................................................81-85 Summary : This study was a retrospective review comparing 88 patients with Merkel cell carcinoma who were treated with surgery alone to those treated with surgery and postoperative radiotherapy to assess for differences in survival. Radiotherapy was not found to be a significant determinant of survival, but when restricted to stage I and II Merkel cell carcinoma (AJCC 7th edition), radiotherapy addition to surgery did significantly improve survival ( p = 0.019). Overall stage, T stage, N stage, and M stage all were found to significantly contribute to survival on univariate analysis. Patient age, gender, primary site, negative margin status, immunosuppression, and history of prior malignancy were not found to significantly contribute to overall survival.

B. Non melanoma skin cancer i. Merkel cell

ii. When to do neck dissection for SCCA, role for sentinel node in SCCA Harris BN, Bayoumi A, Rao S, et al. Factors associated with recurrence and regional adenopathy for head and neck cutaneous squamous cell carcinoma. Otolaryngol Head Neck Surg . 2017; 156(5):863-869. EBM level 4.......................................................................................................86-92 Summary : The subset of patients who present with advanced disease are not well represented by the AJCC 7th edition. This paper examined 212 patients with advanced disease, such as recurrent tumors, perineural invasion (PNI), and depth of invasion > 2 mm, features found in < 5% of patients with cutaneous SCC of the head and neck. In this study, PNI was an independent predictor for recurrence (hazard ratio = 2.62; p = 0.028), and these patients were 2.74 times more likely to present with nodal disease. On multivariate analysis, the poorly differentiated histology was associated with a 2.34 times greater risk for recurrence, and previous treatment was associated with a 2.21 times greater risk for recurrence. Additionally, patients with a primary tumor site on the ear, cheek, temple, or lip were more likely to present with regional metastatic disease. i. Deintensification of therapy Barney CL, Walston S, Zamora P, et al. Clinical outcomes and prognostic factors in cisplatin versus cetuximab chemoradiation for locally advanced p16 positive oropharyngeal carcinoma. Oral Oncol . 2018; 79:9-14. EBM level 3....................................................................................93-98 Summary : Current trends towards using cetuximab over cisplatin to deintensify oropharyngeal cancer treatment occurred prior to the randomized control trial data evaluating these agents. This study is a retrospective evaluation of patients who received either agent with radiotherapy. Cisplatin offered improved locoregional and overall survival compared with cetuximab. Chera BS, Amdur RJ, Tepper JE, et al. Mature results of a prospective study of deintensified chemoradiotherapy for low-risk human papillomavirus-associated oropharyngeal squamous cell carcinoma. Cancer . 2018; 124(11):2347-2354. EBM level 2..................................................99-106 Summary : This study is a prospective phase II trial for treatment of oropharyngeal squamous cell carcinoma with weekly low-dose cisplatin and 60-Gy radiotherapy. Three-year locoregional, disease-free, and overall survival rates were 100%, 100%, 95%, respectively. Quality-of-life and swallowing scores were good. No patients required permanent PEG tubes, though 39% of patients required PEG tubes during therapy. Sethia R, Yumusakhuylu AC, Ozbay I, et al. Quality of life outcomes of transoral robotic surgery with or without adjuvant therapy for oropharyngeal cancer. Laryngoscope . 2018; 128(2):403-411. EBM level 4...............................................................................................................................107-115 Summary : This study prospectively evaluated 111 patients undergoing transoral robotic surgery (TORS) management for oropharyngeal cancer with or without adjuvant therapy. Patients who underwent TORS alone maintained higher quality-of-life and functional scores than patients who received postoperative radiation or chemoradiation. There were no PEG tubes or tracheostomy in the surgery-only treatment cohort.

III. Upper Aerodigestive Tract A. Oropharynx

IV. Endocrine

A. Reclassification of thyroid cancers Baloch ZW, Harrell RM, Brett EM, et al. American Association of Clinical Endocrinologists and American College of Endocrinology disease state commentary: managing thyroid tumors diagnosed as noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Endocr Pract . 2017; 23(9):1150-1155. EBM level 5.......................................................................................................116-121 Summary : This article reviews the recent change in nomenclature for encapsulated follicular variant of papillary thyroid carcinoma to neoplasm with papillary-like nuclear features. This article seeks to address changes in clinical management of patients as a result of these changes, particularly the effect of the change on the risk for cancer for the indeterminant categories on fine-needle biopsy, Bethesda III-V. Also, the issue of reevaluation of previous diagnoses of follicular variant of papillary thyroid cancer is addressed. Summary : This article updates the Bethesda System for Reporting Thyroid Cytopathology for 2017. Major changes include alterations in risks of malignancy, incorporation of molecular testing, and the diagnosis of non-invasive follicular thyroid neoplasm with papillary-like nuclear features. Layfield LJ, Baloch ZW, Esebua M, et al. Impact of the reclassification of the non-invasive follicular variant of papillary carcinoma as benign on the malignancy risk of the Bethesda System for reporting thyroid cytopathology: a meta-analysis study. Acta Cytol . 2017; 61(3):187-193. EBM level 1...............................................................................................................................................128-134 Summary : This article addresses the change in the predicted rate of malignancy for each of the Bethesda category diagnoses for fine-needle aspiration with the recent change in nomenclature for encapsulated follicular variant of papillary thyroid carcinoma to neoplasm with papillary-like nuclear features. The greatest impact is on the categories of atypia of undetermined significance/follicular lesion of undetermined significance, Bethesda category III, and suspicious for malignancy, Bethesda category V. Nikiforov YE, Seethala RR, Tallini G, et al. Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: a paradigm shift to reduce overtreatment of indolent tumors. JAMA Oncol . 2016; 2(8):1023-1029. EBM level 3..................................................................................135-141 Summary : This article refines the pathologic diagnostic criteria for the diagnosis of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) and reviews the outcomes for patients with EFVPTC. Based on the findings from these outcomes studies, this group suggests that this pathologic entity no longer be considered a cancer, and should be renamed non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This change in categorization will facilitate less surgery and avoid radioactive iodine therapy for these patients. B. Molecular testing Roth MY, Witt RL, Steward DL. Molecular testing for thyroid nodules: review and current state. Cancer . 2018; 124(5):888-898. EBM level 5................................................................................142-152 Summary : This paper reviews the development of molecular testing for thyroid nodules and summarizes the current commercial tests available. It highlights the advantages and disadvantages of each test and touches on future directions. Cibas ES, Ali SZ. The 2017 Bethesda System for Reporting Thyroid Cytopathology. Thyroid . 2017; 27(11):1341-1346. EBM level 5.....................................................................................................122-127

Jug RC, Datto MB, Jiang XS. Molecular testing for indeterminate thyroid nodules: performance of the Afirma gene expression classifier and ThyroSeq panel. Cancer Cytopathol . 2018 Apr 10; doi:10.1002/cncy.21993. [Epub ahead of print]. EBM level 3......................................................153-162 Summary : This paper looks at the performance of two common molecular tests for thyroid nodules while taking into account the new diagnosis of non-invasive follicular thyroid neoplasm with papillary-like nuclear features. Additionally, the authors review the ultrasound findings and compare this to their newly calculated rate of malignancy on indeterminate nodules.

Mostoufi-Moab S, Labourier E, Sullivan L, et al. Molecular testing for oncogenic gene alterations in pediatric thyroid lesions. Thyroid . 2018; 28(1):60-67. EBM level 3............................................163-170

Summary : This paper retrospectively evaluates resected thyroid tissue with respect to mutations in the pediatric population. The authors demonstrate that when a mutation is identified, it correlates with malignancy (97%).

V. Lymphatic

A. New staging system García J, López M, López L, et al. Validation of the pathological classification of lymph node metastasis for head and neck tumors according to the 8th edition of the TNM Classification of Malignant Tumors. Oral Oncol . 2017; 70: 29-33. EBM level 4...................................................171-175 Summary : These authors retrospectively studied 1188 patients with head and neck squamous cell carcinoma treated with neck dissection, excluding the HPV-associated oropharyngeal carcinomas. The pathological nodal (pN) stages were determined using both the AJCC 7th edition and 8th editions. Cause-specific survival curves were analyzed; the pN2 and pN3 curves were similar under the 7th edition, but achieved greater distribution under the 8th edition criteria. The authors also found the 5-year cause-specific survival for patients with extracapsular spread (ECS) was 22.4% ,while for patients without ECS it was significantly more favorable at 51.4% ( p = 0.0001). Zhan KY, Eskander A, Kang SY, et al. Appraisal of the AJCC 8th edition pathologic staging modifications for HPV-positive oropharyngeal cancer, a study of the National Cancer Data Base. Oral Oncol . 2017; 73:152-159. EBM level 4.........................................................................................176-183 Summary : Utilization of the National Cancer Data Base for validation of the new AJCC 8th edition restaging of HPV-associated oropharyngeal cancers demonstrated improved hazard discrimination between the stages, thus illustrating the new system’s greater prognostication value. The data presented also demonstrate that nodal size and nodal laterality are not as predictive as nodal count in HPV-associated oropharyngeal carcinomas. The authors note a potential contribution of extracapsular spread for HPV-associated carcinomas; however, this pathologic feature does not confer survival disadvantage across institutions/studies thus far.

VI. Complications

A. Free flaps complication rates Brady JS, Desai SV, Crippen MM, et al. Association of anesthesia duration with complications after microvascular reconstruction of the head and neck. JAMA Facial Plastic Surg . 2018; 20(3):188-195. EBM level 4.....................................................................................................................................184-191 Summary : This article specifically examines the contribution of anesthesia duration during head and neck free flap reconstruction to postoperative complications, using the American College of Surgeons National Surgical Quality Improvement Program database. It provides data showing that increasing anesthesia duration was associated with both medical and surgical complications as well as need for postoperative transfusion. Eskander A, Kang S, Tweel B, et al. Predictors of complications in patients receiving head and neck free flap reconstructive procedures. Otolaryngol Head Neck Surg . 2018; 158(5):839-847. EBM level 4...............................................................................................................................................192-200 Summary : This article assesses the complication rate in a large cohort of patients who underwent free flap reconstructive surgery of the head and neck and the contributing perioperative factors. It highlights the high incidence of both medical and surgical complications experienced by these patients in the postoperative period. The article also identifies potential areas for quality improvement initiatives to reduce these complications. Summary : In this study, the most common sources of infection were the submandibular glands, the parapharyngeal and retropharyngeal spaces, and odontogenic causes. Risk factors for the development of significant complications were diabetes mellitus and multiple neck space involvement. Submandibular and sublingual space infections had the highest incident of airway compromise. Microbacterial aspects, CT scan data, and laboratory and clinical data of these cases were analyzed. Surgical intervention may be most important in patients with such history. Antimicrobial therapy and considerations also are discussed, and the importance of CT scan from neck through to the mediastinum is noted. Cramer JD, Purkey MR, Smith SS, Schroeder JW Jr. The impact of delayed surgical drainage of deep neck abscesses in adult and pediatric populations. Laryngoscope . 2016; 126(8):1753-1760. EBM level 2c.............................................................................................................................................210-217 Summary : This is a multicenter, prospective cohort study of 1012 patients (347 adult, 665 pediatric) with deep neck abscesses who underwent incision and drainage within 7 days of admission. Days to drainage following admission were compared to clinical outcomes with regard to abscess-specific morbidity and mortality. Postoperative abscess-related indictors were sepsis, pneumonia, unplanned intubation, mechanical ventilation for > 48 hours, and death. Surgical site infections, stroke, return to OR, and length of stay also were analyzed. Infectious Disease A. Abscess/infection treatment regarding medical vs surgical therapy Boscolo-Rizzo P, Stellin M, Muzzi E, et al. Deep neck infections: a study of 365 cases highlighting recommendations for management and treatment. Eur Arch Otorhinolaryngol . 2012; 269(4):1241- 1249. EBM level 3..........................................................................................................................201-209

VII.

Dabirmoghaddam P, Mohseni A, Navvabi Z, et al. Is ultrasonography-guided drainage a safe and effective alternative to incision and drainage for deep neck space abscesses? J Laryngol Otol . 2017; 131(3):259-263. EBM level 2+.......................................................................................................218-222 Summary : This is a prospective, single-institution case control study of patients undergoing ultrasound drainage vs surgical drainage of deep neck abscesses over a 1-year period. Sixty cases of deep neck abscesses were blindly assigned to either the ultrasound drainage or open surgical drainage group. Excluded patients included those with poorly defined or multiloculated abscesses, pregnancy, or severe medical comorbidities. The main outcome was that length of hospital stay was significantly shorter in the US-guided group. There was not a significant difference in the need for a second procedure between the comparison groups.

VIII. Nonsurgical A. Salvage therapy (immunotherapy, reirradiation, oligometastatic treatment, etc.)

Alfieri S, Cavalieri S, Licitra L. Immunotherapy for recurrent/metastatic head and neck cancer. Curr Opin Otolaryngol Head Neck Surg . 2018; 26(2):152-156. EBM level N/A.................................223-227

Summary : This article provides a comprehensive review of available clinical trial data pertaining to the use of immunotherapeutic agents for recurrent and metastatic head and neck cancer. The article also summarizes ongoing clinical trials in which immunotherapy is being used for locoregionally recurrent head and neck squamous cell carcinoma. Margalit DN, Schoenfeld JD, Rawal B, et al. Patient-oriented toxicity endpoints after head and neck reirradiation with intensity modulated radiation therapy. Oral Oncol . 2017; 73:160-165. EBM level 4...............................................................................................................................................228-233 Summary : This article reports on complications most pertinent to patient concerns in those undergoing reirradiation for head and neck cancer. The study highlights a high incidence of PEG tube dependence, need for urgent tracheotomy, hospitalization, and soft tissue complications, and provides valuable counseling points for patients.

SECTION 7, FEBRUARY 2019 ADDITIONAL REFERENCES

Agrawal A, Civantos FJ, Brumund KT, et al. [ (99m) Tc]Tilmanocept accurately detects sentinel lymph nodes and predicts node pathology status in patients with oral squamous cell carcinoma of the head and neck: results of a phase III multi-institutional trial. Ann Surg Oncol . 2015; 22(11):3708-3715. Andtbacka RH, Agarwala SS, Ollila DW, et al. Cutaneous head and neck melanoma in OPTiM, a randomized phase 3 trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor for the treatment of unresected stage IIIB/IIIC/IV melanoma. Head Neck . 2016; 38(12):1752- 1758.

Badran K, Jani P, Berman L. Otolaryngologist-performed head and neck ultrasound: outcomes and challenges in learning the technique. J Laryngol Otol . 2014; 128(5):447-453.

Busch EL, Zevallos JP, Olshan AF. Gastroesophageal reflux disease and odds of head and neck squamous cell carcinoma in North Carolina. Laryngoscope . 2016; 126(5):1091-1096.

Carnaby-Mann G, Crary MA, Schmalfuss I, Amdur R. “Pharyngocise”: randomized controlled trial of preventative exercises to maintain muscle structure and swallowing function during head-and-neck chemoradiotherapy. Int J Radiat Oncol Biol Phys . 2012; 83(1): 209-216. Cheung PK, Chin RY, Eslick GD. Detecting residual/recurrent head neck squamous cell carcinomas using PET or PET/CT: systematic review and meta-analysis. Otolaryngol Head Neck Surg . 2016;154(3):421-432.

Choby GW, Kim J, Ling DC, et al. Transoral robotic surgery alone for oropharyngeal cancer: quality-of- life outcomes. JAMA Otolaryngol Head Neck Surg . 2015; 141(6):499-504.

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Reprinted by permission of Cancer. 2018; 124(15):3171-3180.

Original Article

Development of a Novel Salivary Gland Cancer Lymph Node Staging System 2,3 ; Michael Luu, MPH 4 ; Sungjin Kim, MS 4 ; Mourad Tighiouart, PhD 4 ; Jon Mallen-St. Clair, MD, PhD 2,3 ; Emi J. Yoshida, MD 2,5 ; Stephen L. Shiao, MD, PhD 2,5 ; Ilmo Leivo, MD, PhD 6 ; and Zachary S. Zumsteg, MD 2,5 BACKGROUND: Current lymph node (LN) staging for salivary gland cancer (SGC) is extrapolated from mucosal head and neck squa- mous cell carcinoma. However, given its unique biology and clinical behavior, it is possible that a SGC-specific LN staging system would be more accurate. METHODS: Patients from the National Cancer Data Base with nonmetastatic SGC of the head and neck who were diagnosed from 2004 through 2013 and underwent surgical resection and neck dissection removing at least 10 LNs were included. Multivariable models were constructed to assess the association between survival and LN factors, including number of met- astatic LNs, extranodal extension, LN size, and lower LN involvement. RESULTS: Overall, 4520 patients met the inclusion criteria. An increasing number of metastatic LNs was found to be strongly associated with worse survival without plateau. The risk of death increased more rapidly up to 4 LNs (hazard ratio, 1.34; 95% confidence interval, 1.27-1.41 [ P < .001]), and was more gradual for addi- tional LNs > 4 (hazard ratio, 1.02; 95% confidence interval, 1.01-1.03 [ P < .001]). LN size, extranodal extension, and lower LN involve- ment appeared to have no impact on survival when accounting for the number of metastatic LNs. Recursive partitioning analysis was used to create a novel SGC LN staging system in which N0 indicates 0 positive LNs, N1 indicates 1 to 2 positive LNs, N2 indicates 3 to 21 positive LNs, and N3 indicates 22 positive LNs. This system exhibited greater concordance than the current American Joint Com- mittee on Cancer (eighth edition) system. CONCLUSIONS: Quantitative LN burden is an important determinant of survival in patients with SGC. Use of this variable may improve SGC staging. Cancer 2018;000:000–000. V C 2018 American Cancer Society . INTRODUCTION Salivary gland cancers (SGCs) are a rare, heterogeneous collection of malignancies arising from the major or minor salivary glands in the head and neck that are primarily managed surgically. In addition to grade and tumor stage, one of the pri- mary factors associated with disease recurrence and survival in patients with SGC is the presence of lymph node (LN) metastases, 1-4 which may vary in frequency according to the site of the primary tumor. 1,2,5,6 Current LN staging systems for SGC are extrapolated from mucosal head and neck squamous cell carcinoma. 7 However, given that SGC has distinct biology, clinical behavior, and treatment paradigms in comparison with head and neck squamous cell carcinoma, it is pos- sible that LN staging that is specific for patients with salivary malignancies could outperform current methodology. The number of cervical LNs containing metastases is emerging as a powerful predictor of outcome in patients with head and neck cancer. 8-11 In patients with oral cavity cancers, 8 laryngeal cancers, 11 and hypopharyngeal cancers, 11 the number of pathologically positive LNs (LN 1 ) has been shown to strongly correlate with survival, representing a better metric of prognosis than classic LN factors included in the American Joint Committee on Cancer (AJCC) eighth edition staging system such as LN size, laterality, and extranodal extension (ENE). In addition, the AJCC eighth edition patho- logic nodal staging system for patients with p16-positive oropharyngeal cancer is now entirely based on the number of pathologic LNs. However, to the best of our knowledge, less is known regarding the impact of quantitative LN burden in patients with SGC. With this background, we sought to define a novel LN staging system for SGC using data from patients with SGC undergoing surgical resection and neck dissection in the National Cancer Data Base (NCDB). We hypothesized that, sim- ilar to other head and neck cancers, quantitative LN metastatic burden is a central factor for predicting survival outcomes Corresponding author: Zachary S. Zumsteg, MD, Department of Radiation Oncology, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048; zachary.zumsteg@cshs.org 1 Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland; 2 Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California; 3 Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California; 4 Department of Biostatistics and Bioinformatics, Cedars-Sinai Medical Center, Los Angeles, California; 5 Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California; 6 Institute of Biomedicine, Department of Pathology, University of Turku and Turku University Hospital, Turku, Finland Katri Aro, MD, PhD 1,2 ; Allen S. Ho, MD KEYWORDS: lymph nodes, neck dissection, salivary gland cancer, staging.

Additional supporting information may be found in the online version of this article.

DOI: 10.1002/cncr.31535, Received: January 26, 2018; Revised: March 7, 2018; Accepted: April 10, 2018, Published online Month 00, 2018 in Wiley Online Library (wileyonlinelibrary.com)

Cancer

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