2017 Section 7 Green Book

AcademyU ®

| www.entnet.org/hsc

Your Otolaryngology Education Source

Neoplastic and Inflammatory Diseases of the Head and Neck Home Study Course

Hsc Home Study Course

Section 7 February 2017

© 2017 American Academy of Otolaryngology—Head and Neck Surgery Foundation Empowering otolaryngologist-head and neck surgeons to deliver the best patient care

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

February 2017

SECTION 7

Neoplastic and Inflammatory Diseases of the Head and Neck

SECTION FACULTY:

Mark E. Prince, MD ** Bhuvanesh Singh, MD PhD ** Jeffrey S. Wolf, MD, FACS** Salvatore M. Caruana, MD Ted H. Leem, MD, MS, FACS

Matthew O. Old, MD Bradley Schiff, MD

American Academy of Otolaryngology - Head and Neck Surgery Foundation

Section 7 exam deadline: March 13, 2017 Expiration Date: August 4, 2017; 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. 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. 1. Evaluate the benefits and limitation of in office ultrasound use by otolaryngologists. 2. Define the role of ultrasound in assessing thyroid/parathyroid and neck disease. 3. Recognize role of PET and PET/CT in the diagnosis and management of head and neck cancer. 4. Define role of PET-CT in the management and outcome of oropharynx cancers. 5. Incorporate preventive exercises to maintenance of structure and swallowing in patients undergoing chemoradiation therapy for head and neck cancers. 6. Consider high risk for late effects of chemoradiation treatment for head neck cancer on swallowing function. 7. Explain impact of prophylactic central neck dissection on risk for locoregional failure in head and neck cancers. 8. Consider role of radioactive iodine in development of second primary malignancies. 9. Describe association between thyroid cancer incidence and ease of access to health care. 10. Define role of sentinel node biopsies in management of oral and cutaneous squamous cell carcinomas. 11. Recognize effects of head and neck cancer of Health-related quality of life. 12. Define role of surgery in the management of oropharyngeal squamous cell carcinomas. 13. Define role of novel systemic and injected therapies in the treatment of melanoma and thyroid cancer. 14. Explain effects of gastroesophageal reflux disease of the risk for head neck cancer. 15. Recognize effects of treatment with proton pump inhibitors and histamine 2 blockers on overall survival in patients with head and neck cancer. 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. Outcomes Objectives The participant who has successfully completed this section should be able to:

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 a 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

2016-17 Section 7 NEOPLASTIC AND INFLAMMATORY DISEASES OF THE HEAD AND NECK FACULTY

** Co-Chairs: Mark E. Prince, MD, Professor and Interim Chair, Department of Otolaryngology-HNS, University of Michigan, Ann Arbor, Michigan Disclosure: No relationships to disclose Bhuvanesh Singh, MD PhD , Director, Laboratory of Epithelial Cancer Biology; Director, Speech and Hearing Center; Attending Surgeon, Head and Neck Service, Memorial Sloan-Kettering Cancer Center; Professor of Otolaryngology, Weill Medical College of Cornell University, New York, New York Disclosure: No relationships to disclose Jeffrey S. Wolf, MD, FACS Associate Professor and Medical Director; Associate Chair of Clinical Practice; Otolaryngology-Head and Neck Surgery Program in Oncology, University of Maryland School of Medicine, Baltimore, Maryland Disclosure: Stock/Stock options: Maryland Development Center; Stock/Stock options: Tesserae Medical LLC; Stock/Stock Options: Aerea Medical LLC; Intellectual Property Rights: Tesserae Medical LLC. 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 Ted H. Leem, MD, MS, FACS , Southern California Permanente Medical Group Downey, California Disclosure: No relationships to disclose Matthew O. Old, MD, FACS, Assistant Professor, Department of Otolaryngology-Head and Neck Surgery, The James Cancer Hospital and Solove Research Institute, Wexner Medical Center at The Ohio State University, Columbus, Ohio Disclosure: No relationships to disclose Bradley Schiff, MD , Associate Professor Department of Otorhinolaryngology-Head and Neck Surgery, Albert Einstein College of Medicine, Bronx, New York Disclosure: No relationships to disclose.

Planner(s): Linda Lee, AAO─HNSF Education Senior Manager Stephanie Wilson, Stephanie Wilson Consulting, LLC;

No relationships to disclose No relationships to disclose

Production Manager Alfred A. Simental, Jr, MD

No relationships to disclose

Richard V. Smith, MD, chair, Head and Neck Surgery Education

Expert Witness: Various legal firms

This 2017 Home Study Course Section 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 13, 2017: Suggested section 7 Exam submission deadline; course closed August 4, 2017.

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.

O UTLINE

FEBRUARY 2017 SECTION 7 NEOPLASTIC AND INFLAMMATORY DISEASES OF THE HEAD AND NECK

I.

HEAD AND NECK ULTRASOUND

II. APPLICATION OF PET/CT/MRI IN MANAGEMENT OF HEAD AND NECK CANCER

III.

COMPLICATIONS: DYSPHAGIA PREVENTION AND MANAGEMENT AFTER THERAPY FOR HEAD AND NECK CANCER

IV.

MANAGEMENT OF THYROID NODULES AND THYROID MALIGNANCY

V.

LYMPHATIC SYSTEM: SENTINEL NODE BIOPSY

VI.

QUALITY OF LIFE

VII.

TREATMENT MODALITIES UPDATE: ROBOTIC SURGERY

VIII. TREATMENT MODALITIES UPDATE: IMMUNOTHERAPY

IX.

INFLAMMATORY: GERD ROLE IN CANCER DEVELOPMENT AND PREVENTION

T ABLE OF C ONTENTS Selected Recent Materials - Reproduced in this Study Guide

FEBRUARY 2017 SECTION 7 NEOPLASTIC AND INFLAMMATORY DISEASES OF THE HEAD AND NECK

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

I.

Head and Neck Ultrasound 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. EBM level 3............................................................................................................................1-7 Summary : This is a very compelling study describing the experience of a single otolaryngologist head and neck surgeon who follows all necessary steps to become certified in head and neck ultrasonography. The subject then reports his results as far as accuracy by referencing his first 250 patients and his interpretations of their ultrasounds. He then had his radiologist collaborator review the ultrasounds and compare accuracy rates between them. The study demonstrates that in this one individual case, the radiologist-interpreted ultrasound had a lower false-negative rate and was somewhat more accurate. The accuracy of the otolaryngologist-performed ultrasound was still very good. This study highlights the potential difficulties of attempting to train otolaryngologist head and neck surgeons to add ultrasound to their armamentarium and expect that they will perform with similar accuracy and results to radiology-trained physicians. Mazzaglia PJ. Surgeon-performed ultrasound in patients referred for thyroid disease improves patient care by minimizing performance of unnecessary procedures and optimizing surgical treatment. World J Surg . 2010; 34(6):1164-1170. EBM level 3..........................8-14 Summary : This is a single institutional experience of an individual surgeon performing in-office ultrasound and comparing his results to those of outside ultrasounds received with the patient referrals. There were 344 consecutive patients in this study. In 64 of these patients, the surgeon’s ultrasound and interpretation differed from that of the outside radiology-performed ultrasound. These results significantly and favorably affected patient care. Although not randomized, the study does argue strongly that surgeons focused on the thyroid-parathyroid axis can detect disease and determine non- surgical or surgical action at least as well or probably better than radiology-performed neck ultrasound. This study is single armed and has short follow up. Oltmann SC, Schneider DF, Chen H, Sippel RS. All thyroid ultrasound evaluations are not equal: sonographers specialized in thyroid cancer correctly label clinical N0 disease in well differentiated thyroid cancer. Ann Surg Oncol . 2015; 22(2):422-428. EBM level 3.......15-21 Summary : This is a retrospective review of the prospectively collected database at a single institution. Surgeon-performed ultrasound was compared with non-surgeon–performed ultrasound for detecting involved cervical lymph nodes in the setting of thyroid disease. In this study, the surgeon was more than twice as successful at detecting metastatic lymph node disease compared to non-surgeon ultrasonography. The surgeon-performed ultrasound directly correlated to a much lower postoperative recurrence rate. The study has some limitations in that the control group is poorly defined. The strength is that there was a significant follow-up period.

II.

Application of PET/CT/MRI in Management of Head and Neck Cancer 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. EBM level 2...............................................................22-33

Summary : This paper looks at PET/CT for detecting residual/recurrent head and neck squamous cell carcinoma. The study is a meta-analysis that found that PET/CT has high sensitivity and specificity.

Ryu IS, Roh JL, Kim JS, et al. Impact of 18 F-FDG PET/CT staging on management and prognostic stratification in head and neck squamous cell carcinoma: a prospective observational study. Eur J Cancer . 2016; 63:88-96. EBM level 2..................................34-42 Summary : This paper prospectively examines how adding PET/CT to the work up of head and neck squamous cell carcinoma patients affects management and prognosis. The authors found that PET/CT changed the TNM stage in about one-third of patients, PET/CT work-up was more accurate than conventional work up, and patients upstaged by PET/CT work-up had a worse prognosis. Taghipour M, Sheikhbahaei S, Marashdeh W, et al. Use of 18 F-fludeoxyglucose-positron emission tomography/computed tomography for patient management and outcome in oropharyngeal squamous cell carcinoma: a review. JAMA Otolaryngol Head Neck Surg . 2016; 142(1):79-85. EBM level 3......................................................................................43-49 III. Complications: Dysphagia Prevention and Management After Therapy for Head and Neck Cancer 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. EBM level 1.............................................................................................50-59 Summary : This is a randomized controlled trial of 58 patients undergoing chemoradiation therapy (CRT) for head and neck cancer. Comparison groups were sham swallowing exercises, no exercises, and intense swallowing therapy during treatment. As measured by clinical swallowing outcome and by muscle bulk of the genioglossus and hyoglossus and mylohyoid muscles as determined by T2- weighted MRI, the intense therapy group did much better and had reduced muscle atrophy relative to the other groups. A short follow up, well-done study. Peng KA, Kuan EC, Unger L, et al. A swallow preservation protocol improves function for veterans receiving chemoradiation for head and neck cancer. Otolaryngol Head Neck Surg . 2015; 152(5): 863-867. EBM level 3.................................................................................60-64 Summary : This is a retrospective study looking at all patients treated for head and neck cancer with chemoradiation therapy (CRT) and comparing the swallowing outcomes of patients who were compliant with swallowing therapy during treatment with those who were not compliant. Patients who were not compliant with speech and swallowing exercises during and after treatment did worse than patients who were compliant with regard to swallowing function as documented by FOSS scores in these groups. This study demonstrates that swallow rehabilitation and exercise can improve functional outcomes for patients receiving CRT or radiation therapy for head and neck cancer. Summary : This paper presents a literature on the use of PET/CT in oropharyngeal squamous cell carcinoma.

Ward MC, Adelstein DJ, Bhateja P, et al. Severe late dysphagia and cause of death after concurrent chemoradiation for larynx cancer in patients eligible for RTOG 91-11. Oral Oncol . 2016; 57:21-26. EBM level 3................................................................................65-70 Summary : This paper reports on the results of a retrospective cohort study of all patients treated for larynx cancer at a single institution who would have met criteria for the 91-11 trial. Patients were carefully followed for the development of severe late dysphagia that developed after 5 years of follow up and therefore not reported in that trial. They identified that 26% of patients developed severe late dysphagia as a result of therapy after 5 years of follow up. Management of Thyroid Nodules and Thyroid Malignancy Ito Y, Miyauchi A, Inoue H, et al. An observational trial for papillary thyroid microcarcinoma in Japanese patients. World J Surg . 2010; 34(1):28-35. EBM level 2..................................................................................................................................71-78 Summary : This is a prospective case-controlled study comparing observation versus surgical intervention for patients with papillary thyroid microcarcinoma. The results show that observation is adequate for many, and that progression during observation does not adversely affect survival or salvage rates. Lang BH, Ng SH, Lau LL, et al. A systematic review and meta-analysis of prophylactic central neck dissection on short-term locoregional recurrence in papillary thyroid carcinoma after total thyroidectomy. Thyroid . 2013; 23(9):1087-1098. EBM level 1......................79-90 Summary : This is a meta-analysis of the locoregional recurrence and complications in patients who underwent prophylactic central neck dissection compared to those who did not. Evidence shows the benefit of the prophylactic central neck dissection in patients with N0 neck. Locoregional recurrence was reduced in patients undergoing central neck dissection. Lang BH, Wong IO, Wong KP, et al. Risk of second primary malignancy in differentiated thyroid carcinoma treated with radioactive iodine therapy. Surgery . 2012; 151(6):844-850. EBM level 2........................................................................................................................91-97 Summary : Retrospective study of all patients treated with radioactive iodine (RAI) for differentiated thyroid cancer (DTC) within a single healthcare system in China. The 895 patients identified for study were followed for a minimum of 2 years; 645 patients received RAI as part of their treatment, while 249 patients did not. Controlling for other factors, RAI-positive and RAI-negative patients were compared the subsequent developments of second primary malignancies (SPMs). A statistically significant deference in the incidence of SPMs was noted in the RAI group, while the RAI-negative group had baseline levels of SPM development (13.5% vs 3.1%; p = 0.015). This study is one of several that strongly suggest that RAI therapy can have significant long-term effects on patients receiving this therapy and indirectly argues that RAI should be given selectively.

IV.

Morris LG, Sikora AG, Tosteson TD, Davies L. The increasing incidence of thyroid cancer: the influence of access to care. Thyroid . 2013; 23(7):885-891. EBM level 1...............98-104

Summary : This study uses the SEER database and correlates the well-recognized increased incidence of papillary thyroid cancer (PTC) diagnosis in the U.S. to the availability of and access to healthcare among the more affluent population. The study, in conjunction with others, shows that the majority of the increased cases of PTC are from small, likely indolent, PTCs, and is driven by increased detection in an already existing pool of patients with subclinical disease.

V.

Lymphatic System: Sentinel Node Biopsy 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. EBM level 1.............................................................105-112 Summary : Sentinel lymph node biopsy using [99mTc]tilmanocept accurately predicted nodal status in oral cavity head and neck squamous cell carcinoma with a low false-negative rate, high negative predicative value, and high accuracy. This study demonstrates this may be a method used in conjunction with or in lieu of elective neck dissection, but future studies are warranted. Durham AB, Lowe L, Malloy KM, et al. Sentinel lymph node biopsy for cutaneous squamous cell carcinoma on the head and neck. JAMA Otolaryngol Head Neck Surg . 2016; 142(12):1171-1176. EBM level 4..................................................................................113-118 Summary : This study conducted a retrospective review of sentinel lymph node biopsy in cutaneous squamous cell carcinoma. Analysis by serial step sectioning and immunohistochemistry increased the sentinel lymph node biopsy positivity rate to 15.1%.

Mehta V, Nathan CA. What is the role of sentinel lymph node biopsy in early-stage oral cavity carcinoma? Laryngoscope . 2016; 126(1):9-10. EBM level 4...........................119-120

Summary : This paper presents a review of the role of sentinel lymph node biopsy in early-stage oral cavity carcinoma.

Schilling C, Stoeckli SJ, Haerle SK, et al. Sentinel European Node Trial (SENT): 3-year results of sentinel node biopsy in oral cancer. Eur J Cancer . 2015; 51(18):2777-2784. EBM level 2..............................................................................................................................121-128

Summary : This is a prospective study of sentinel lymph node biopsy in oral cancer. The results show excellent sensitivity, positive predicative value, and survival when employed for oral cancer.

VI.

Quality of Life Reeve BB, Cai J, Zhang H, et al. Factors that impact health-related quality of life over time for individuals with head and neck cancer. Laryngoscope . 2016; 126(12):2718-2725. EBM level 4..............................................................................................................................129-136 Summary : This study is a population-based longitudinal cohort study which attempts to identify sociodemographic, behavioral, and clinical factors associated with health-related quality of life (HRQOL) for head and neck cancer patients over time by administering a questionnaire at baseline, 22 months, and 42 months. Its strength is the largenumber of patients (587). Rettig EM, D'Souza G, Thompson CB, et al. Health-related quality of life before and after head and neck squamous cell carcinoma: analysis of the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey linkage. Cancer . 2016; 122(12):1861-1870. EBM level 4....................................................................................................................137-146 Summary : Quality of life (QOL) for older individuals with head and neck squamous cell carcinoma was examined using the SEER database. The records of 1653 patients were examined. The authors noted that QOL declines both before and after head and neck squamous cell carcinoma, and any observed posttreatment recovery is likely an artifact of shorter survival among individuals with the lowest QOL.

Sethugavalar B, Teo MT, Buchan C, et al. Impact of prophylactic gastrostomy or reactive NG tube upon patient-reported long term swallow function following chemoradiotherapy for oropharyngeal carcinoma: a matched pair analysis. Oral Oncol . 2016; 59:80-85. EBM level 3..............................................................................................................................147-152 Summary : This study is a retrospective matched-pair analysis looking at patient-reported long-term swallow function following chemoradiotherapy for locally advanced oropharyngeal cancer in relation to the use of a prophylactic gastrostomy or reactive nasogastric tube. The authors found that patients with prophylactic use of a gastrostomy tube had worse long-term swallow function. Treatment Modalities Update: Robotic Surgery 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. EBM level 4..............................................................................................................................153-158 Summary : This is a retrospective cohort of patients treated with primary surgery (transoral robotic surgery) for oropharyngeal squamous cell carcinoma followed by adjuvant therapy if indicated. The results demonstrate high quality-of-life scores and low gastrostomy tube placement rates. Kumar B, Cipolla MJ, Old MO, et al. Surgical management of oropharyngeal squamous cell carcinoma: survival and functional outcomes. Head Neck . 2016; 38 Suppl 1:E1794-1802. EBM level 3....................................................................................................................159-167 Summary : This is a large case series of surgically managed oropharyngeal squamous cell carcinoma. The authors demonstrated the superiority of the transoral approach over the open approach, and also delineated novel patient stratifications based on patient and tumor characteristics. Surgery appeared to negate the negative impact smoking and neck disease typically imparts for oropharyngeal squamous cell carcinoma patients. VIII . Treatment Modalities Update: Immunotherapy 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. EBM level 2..................................168-174 Summary : This study looks at intralesional injection of unresectable stage IIIB/IIIC/IV melanoma with the oncolytic virus talimogene laherparepvec. Durable response rate was higher for talimogene laherparepvec–treated patients than for granulocyte-macrophage colony-stimulating factor treated patients (36.1% vs 3.8%; p = 5.001). Yimaer W, Abudouyimu A, Tian Y, et al. Efficacy and safety of vascular endothelial growth factor receptor tyrosine kinase inhibitors in the treatment of advanced thyroid cancer: a meta- analysis of randomized controlled trials. Onco Targets Ther . 2016; 9:1167-1173. EBM level 1..............................................................................................................................175-181 VII.

Summary : This paper is a meta-analysis of randomized controlled trials looking at vascular endothelial growth factor receptor tyrosine kinase inhibitors.

IX.

Inflammatory: GERD Role in Cancer Development and Prevention 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. EBM level 3....................................................................................................................182-187 Summary : This study is a large population case-control study of head and neck cancer in North Carolina. The authors found no increased odds of head and neck cancer with self-reported heartburn symptoms or self-reported medical diagnosis of gastroesophageal reflux disease. These results held true for subgroup analysis for specific tumor sites as well. Papagerakis S, Bellile E, Peterson LA, et al. Proton pump inhibitors and histamine 2 blockers are associated with improved overall survival in patients with head and neck squamous carcinoma. Cancer Prev Res (Phila) . 2014; 7(12):1258-1269. EBM level 3..............188-199 Summary : This is a large prospective cohort of head and neck squamous cell carcinoma patients in which histamine receptor-2 antagonists (H2RAs) and proton pump inhibitor (PPI) use and treatment outcomes were examined. The findings demonstrated that both medications were significant prognostic factors for overall survival ,but that only H2RAs were associated with recurrence-free survival in HPV16-positive oropharyngeal squamous cell carcinoma patients.

2017 SECTION 7 ADDITIONAL REFERENCES

Alexander EK, Schorr M, Klopper J, et al. Multicenter clinical experience with the Afirma gene expression classifier. J Clin Endocrinol Metab . 2014; 99(1):119-125.

Ali S, Palmer FL, Yu C, et al. A predictive nomogram for recurrence of carcinoma of the major salivary glands. JAMA Otolaryngol Head Neck Surg . 2013; 139(7):698-705.

Almeida JP, Sanabria AE, Lima EN, Kowalski LP. Late side effects of radioactive iodine on salivary gland function in patients with thyroid cancer. Head Neck . 2011; 33(5):686-690.

Annane D, Depondt J, Aubert P, et al. Hyperbaric oxygen therapy for radionecrosis of the jaw: a randomized, placebo-controlled, double-blind trial from the ORN96 study group. J Clin Oncol . 2004; 22(4):4893-4900.

Asher SA, White HN, Kejner AE, et al. Hemorrhage after transoral robotic-assisted surgery. Otolaryngol Head Neck Surg . 2013; 149(1):112-117.

Bhatti RM, Stelow EB. IgG4-related disease of the head and neck. Adv Anat Pathol . 2013; 20(1):10-16.

Caudell JJ, Schaner PE, Meredith RF, et al. Factors associated with long-term dysphagia after definitive radiotherapy for locally advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys . 2009; 73(2):410- 415.

Chang JS, Lo HI, Wong TY, et al. Investigating the association between oral hygiene and head and neck cancer. Oral Oncol . 2013; 49(10):1010-1017.

Chen AM, Chen LM, Vaughan A, et al. Head and neck cancer among lifelong never-smokers and ever- smokers: matched-pair analysis of outcomes after radiation therapy. Am J Clin Oncol . 2011; 34(3):270- 275. Chen AM, Daly ME, Farwell DG, et al. Quality of life among long-term survivors of head and neck cancer treated by intensity-modulated radiotherapy. JAMA Otolaryngol Head Neck Surg . 2014; 140(2):129-133.

Chia SH, Gross ND, Richmon JD. Surgeon experience and complications with Transoral Robotic Surgery (TORS). Otolaryngol Head Neck Surg . 2013; 149(6):885-892.

Cibas ES, Ali SZ. The Bethesda System for reporting thyroid cytopathology. Thyroid . 2009; 19(11):1159-1165.

Dziegielewski PT, Tekno, TN, Durmus K, et al. Transoral robotic surgery for oropharyngeal cancer: long-term quality of life and functional outcomes. JAMA Otolaryngol Head Neck Surg . 2013; 139(11):1099-1108.

Erman AB, Collar RM, Griffith KA, et al. Sentinel lymph node biopsy is accurate and prognostic in head and neck melanoma. Cancer . 2012; 118(4):1040-1047.

Ettl T, Gosau M, Brockhoff G, et al. Predictors of cervical lymph node metastasis in salivary gland cancer. Head Neck . 2014; 36(4):517-523.

i

Giordano D, Valcavi R, Thompson GB, et al. Complications of central neck dissection in patients with papillary thyroid carcinoma: results of a study on 1087 patients and review of the literature. Thyroid . 2012; 22(9):911-917.

Hamdan AL, Sarieddine D. Laryngeal manifestations of rheumatoid arthritis. Autoimmune Dis . 2013; doi:10.1155/2013/103081. [Epub ahead of print].

Herman MP, Werning JW, Morris CG, et al. Elective neck management for high-grade salivary gland carcinoma. Am J Otolaryngol . 2013; 34(3):205-208.

King SN, Dunlap NE, Tennant PA, Pitts T. Pathophysiology of radiation-induced dysphagia in head and neck cancer. Dysphagia . 2016; 31(3):339-351.

Koss SL, Russell MD, Leem TH, et al. Occult nodal disease in patients with failed laryngeal preservation undergoing surgical salvage. Laryngoscope . 2014; 124(2):421-428.

Kupferman ME, Kubik MW, Bradford CR, et al. The role of sentinel lymph node biopsy for thin cutaneous melanomas of the head and neck. Am J Otolaryngol . 2014; 35(2):226-232.

Langevin SM, Michaud DS, Marsit CJ, et al. Gastric reflux is an independent risk factor for laryngopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev . 2013; 22(6):1061-1068.

Manzoor NF, Russell JO, Bricker A, et al. Impact of surgical resection on survival in patients with advanced head and neck cancer involving the carotid artery. JAMA Otolaryngol Head Neck Surg . 2013; 139(11):1219-1225. 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.

Nixon IJ, Wang LY, Ganly I, et al. Outcomes for patients with papillary thyroid cancer who do not undergo prophylactic central neck dissection. Br J Surg . 2016; 103(3):218-225.

Pisanu A, Porceddu G, Podda M, et al. Systematic review with meta-analysis of studies comparing intraoperative neuromonitoring of recurrent laryngeal nerves versus visualization alone during thyroidectomy. J Surg Res . 2014; 188(1):152-161.

Sawka AM, Thabane L, Parlea L, et al. A second primary malignancy risk after radioactive iodine treatment for thyroid cancer: a systematic review and meta-analysis. Thyroid . 2009; 19(5):451-457.

Sekulic A, Migden MR, Oro AE, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med . 2012; 366(23):2171-2179.

Seup Kim B, Kang KH, Park SJ. Robotic modified radical neck dissection by bilateral axillary breast approach for papillary thyroid carcinoma with lateral neck metastasis. Head Neck . 2015; 37(1):37-45.

Sharma A, Patel S, Baik FM, et al. Survival and gastrostomy prevalence in patients with oropharyngeal cancer treated with transoral robotic surgery vs chemoradiotherapy. JAMA Otolaryngol Head Neck Surg . 2016; 142(7):691-697.

ii

Strychowsky JE, Sommer DD, Gupta MK, et al. Sialendoscopy for the management of obstructive salivary gland disease: a systematic review and meta-analysis. Arch Otolaryngol Head Neck Surg . 2012; 138(6):541-547.

Sun GH, Peress L, Pynnonen MA. Systematic review and meta-analysis of robotic vs conventional thyroidectomy approaches for thyroid disease. Otolaryngol Head Neck Surg . 2014; 150(4):520-532.

Vashishta R, Gillespie MB. Salivary endoscopy for idiopathic chronic sialadenitis. Laryngoscope . 2013; 123(12):3016-3020.

VanderWalde NA, Meyer AM, Deal AM, et al. Effectiveness of chemoradiation for head and neck cancer in an older patient population. Int J Radiat Oncol Biol Phys . 2014; 89(1):30-37.

Wang TS, Cheung K, Farrokhyar F, et al. A meta-analysis of the effect of prophylactic central compartment neck dissection on locoregional recurrence rates in patients with papillary thyroid cancer. Ann Surg Oncol . 2013; 20(11):3477-3483.

Zhang Y, Dai J, Wu T, et al. The study of the coexistence of Hashimoto’s thyroiditis with papillary thyroid carcinoma. J Cancer Res Clin Oncol . 2014; 140(6):1021-1026.

iii

Reprinted by permission of J Laryngol Otol. 2014; 128(5):447-453.

MAIN ARTICLE

The Journal of Laryngology & Otology (2014) , 128 , 447 – 453 .

© JLO (1984) Limited, 2014 doi:10.1017/S0022215114000760

Otolaryngologist-performed head and neck ultrasound: outcomes and challenges in learning the technique

K BADRAN 1 , P JANI 1 , L BERMAN 2

Departments of 1 ENT and 2 Radiology, Addenbrooke ’ s Hospital, Cambridge, UK

Abstract Objective : To assess the feasibility and accuracy of otolaryngologist-performed ultrasound in evaluating head and neck pathology. Method : An ENT trainee, who had undergone basic training in neck ultrasonography, performed this on patients referred with suspected neck pathology. The trainee recorded the presence and nature of any abnormality. Findings were compared with those from a repeated scan performed by an experienced head and neck radiologist. Results : The study included 250 patients. The absence or presence of lesion as reported by the trainee correlated with the radiologist ’ s findings in 207 cases (83 per cent). There were 144 true positives, 63 true negatives, 32 false negatives and 11 false positives, yielding a sensitivity of 82 per cent, specificity of 85 per cent and accuracy of 83 per cent. Of the 144 true positive lesions, 81 per cent were interpreted concordantly with the radiologist. Conclusion : Neck ultrasonography performed by an otolaryngologist is less accurate than that performed by an experienced radiologist, but is still a useful adjunct to clinical assessment, facilitating assessment in a ‘ one-stop ’ clinical setting.

Key words: Ultrasonography; Neck; Abnormalities; Otolaryngology

Introduction Ultrasound is a valuable diagnostic tool used in many areas of medicine. It has been described as quick, port- able, non-invasive and cost effective, and does not involve ionising radiation. 1 – 3 In mainland Europe, it is almost the exception for the radiologist rather than the clinician to perform ultrasound in some specialties. However, in the UK, with the exception of obstetric ultrasound, radiologists and radiographically trained sonographers have traditionally provided a service from centralised departments of radiology, where equipment and manpower can be concentrated cost- effectively. There are increasing demands for other medical spe- cialists to utilise ultrasound as a direct adjunct to clinical examination, and in some specialties it is becoming an integral part of the physician ’ s diagnostic armamentarium and training. This trend is likely to be exacerbated by the increase in referrals and shortage of radiologists. 4 A recent survey distributed by ENT UK discussed the prospects and usefulness of British otolaryngologists learning this skill. Additionally, there is a demand by some European training boards to incorporate ultrasound into clinical training and

accreditation. The Royal College of Radiologists recog- nises that it is appropriate for medical practitioners other than clinical radiologists to develop skills in ultrasound. 5 The role of head and neck ultrasound performed by the ENT clinician, and the ability of the clinician to carry out the ultrasound and accurately interpret the findings, have not been investigated. This prospective study essentially describes the learning process of an ENT trainee with no previous specialist imaging experience, in acquiring neck ultrasound skills. An ENT trainee attended head and neck ultrasound ses- sions in the radiological ultrasound department of a large teaching hospital for 12 months. A well-estab- lished 2-day practical ultrasound course (The Head and Neck Ultrasound Workshop, Morriston Hospital, Swansea) provided a basic introduction. Thereafter, the trainee attended several sessions with one of the course faculty members, observing neck ultrasound examinations. Informal tutorials covered physics and Materials and methods Training

Accepted for publication 13 August 2013

1

K BADRAN, P JANI, L BERMAN

instrumentation, and ultrasound anatomy of the neck. Early practical experience was gained by practising on normal volunteer colleagues. Following this induction, the trainee worked along- side a consultant radiologist with over two decades of experience in head and neck ultrasound (LB). This con- sultant radiologist works closely with all clinical departments at our centre, including surgery, endocrin- ology and oncology, helping with the management of patients. Ultrasound sessions included a weekly dedi- cated ‘ head and neck lump ’ clinic. These sessions include patients with no palpable mass, which typically involves a search for an undiagnosed parathyroid lesion in a patient with hypercalcaemia. This arrangement afforded the trainee one-to-one mentorship. Following the studies of normal volunteers, the second stage of the learning process involved 50 ultra- sound examinations of clinical referrals observed by the radiologist. All examinations were repeated by the radiologist who provided immediate feedback to the trainee. These 50 examinations were excluded from the final analysis of the 250 cases that comprise the current study. If any aspect of the trainee ’ s examination was considered technically suboptimal, and where time constraints permitted, the scan was repeated by the ENT trainee following the radiologist ’ s study. Learning objectives included the identification of variations in normal neck structures and anatomical relationships, the recognition of any deviation from normal, and correct interpretation of an abnormality. A systematic approach to examination was emphasised. This included comprehensive scanning of neck ana- tomical triangles, comparing both sides of the neck, and use of Doppler ultrasound where appropriate. Teaching included advanced use of the machine con- trols, to a much higher level than usually achieved by practitioners other than radiologists or sonographers. Main study After the induction and training period described above, the trainee undertook examinations on patients referred to the neck ultrasound clinic. The trainee ’ s study and conclusion was compared with the examin- ation and conclusion of the radiologist. The ‘ gold standard ’ was taken to be the radiologist ’ s report rather than eventual surgical or histological diagnosis if biopsy or surgery was undertaken. Examinations were performed with Toshiba Aplio XG ultrasound apparatus (Toshiba Medical Systems, Crawley, UK) using appropriate high-frequency linear array transducers. All patients referred with palpable neck masses were included. Scans were undertaken with the patient in a semi-recumbent position with neck extension. Following the scan, the trainee completed a pro- forma, on which the trainee indicated the presence or absence of a lesion, and commented on its nature and significance. If the lesion was considered indetermin- ate, the most likely diagnosis was described. Minor

TABLE I OUTCOME CATEGORIES AND DEFINITIONS

Category

Definition

True negative

No lesion is detected by trainee or radiologist; patient is reassured on same visit Lesion is detected by both trainee & radiologist; trainee is asked to interpret nature of lesion Lesion is not detected (i.e. is missed) by trainee but is detected by radiologist

True positive

False negative

False positive Lesion is ‘ detected ’ by trainee but not radiologist; typically a normal structure misinterpreted as pathological Misinterpretation Lesion is detected by both trainee & radiologist (i.e. true positive), but nature of lesion is misinterpreted by trainee

findings (e.g. reactive lymph nodes) were considered as lesions and were included in our analysis. The radiologist repeated the study and completed a similar proforma. It was not possible to blind the radiologist to the ultrasound findings described by the trainee because of time con- straints and the evaluation process: as part of the evalu- ation, the radiologist scrutinised, and, if necessary, criticised and corrected the trainee ’ s scanning technique. Anonymised data were entered into a database. Results were placed in one of five categories ( Table I ): true negative (normal study), true positive (abnormal study), false negative (missed abnormality), false positive (normal study misinterpreted as abnor- mal), and misinterpretation (abnormality detected, but the nature or significance misinterpreted). There were therefore two aspects to the trainee ’ s assessment. Firstly, identifying whether an abnormality was present, and secondly correctly interpreting any abnor- mal findings. Results A total of 250 consecutive patients with suspected head and neck masses who attended over a 12-month period were included in the study. The median patient age was 50 years, with a male to female ratio of 1:1.7. The range of clinically suspected pathologies at the time of refer- ral is shown in Table II . Scans performed by the trainee indicated a positive finding in 155 patients. The findings of radiological repeat examinations concurred with the trainee ’ s study in 144 examinations (true positives). Eleven of

TABLE II SUSPECTED PATHOLOGY

Diagnosis on referral

Patients ( n (%))

Anterior triangle lump Posterior triangle lump

72 (29) 26 (10) 60 (24) 37 (15) 37 (15) 18 (7)

Thyroid Parotid

Submandibular or submental

Parathyroid

Total

250 (100)

2

OTOLARYNGOLOGIST-PERFORMED HEAD AND NECK ULTRASOUND

TABLE III TRAINEE FALSE POSITIVE RESULTS ∗

Pathology

Trainee ’ s misinterpretation

Radiologist ’ s correct impression

Normal structure misinterpreted as pathological

Thyroid Thyroid

Thyroiditis

Normal Normal

Normal thyroid gland but thickened isthmus Normal heterogeneous thyroid gland Normal section in lower thyroid lobe

Thyroid nodule

Parathyroid Parathyroid

Adenoma Adenoma

No adenoma No adenoma

Normal section in oesophagus Normal section in hyoid bone

Submandibular † Submandibular Submandibular Submandibular

Stone

Normal Normal Normal Normal

Dilated duct Dilated duct

Normal section in mylohyoid muscle Normal section in blood vessel

Impinging ranula (mylohyoid defect)

Normal section in blood vessel passing through mylohyoid

Anterior

LN

Normal

Normal section in SCM

triangle †

∗ 11 patients. † n = 2. LN = lymph node; SCM = sternocleidomastoid muscle

the trainee ’ s 155 ‘ positive ’ findings were considered normal by the radiologist and were therefore deemed to be false positives ( Table III ). The trainee examination indicated a negative finding in 95 patients. The radiologist ’ s repeat examination indicated normal findings in 63 patients (true nega- tives). Therefore, according to the radiologist gold standard, the trainee missed abnormalities in 32 (34 per cent) of the abnormal scans (false negatives). These abnormalities included palpable and impalpable neck masses ( Tables IV and V ). Of the trainee ’ s 144 true positives, the trainee ’ s inter- pretation of the lesion was concordant with that of the radiologist in 117 (81 per cent) of the abnormal scans. The trainee ’ s interpretation of detected pathology was considered a misinterpretation in 28 cases (19 per cent of all abnormal scans) ( Table VI ). Using the radiological opinion as a gold standard, the overall figures for sensitivity, specificity, positive predictive value, negative predictive value and accur- acy of the trainee examinations were: 82, 85, 93, 67 and 83 per cent, respectively. Of all the 250 examinations, we were able to reassure 127 patients by excluding serious pathology (50 patients) or excluding any lesion (77 patients). Only 16 patients required biopsies, of which 10 proved to be malignant. Of the 16 patients that underwent biopsy, the trainee failed to detect 1 malignant lesion

(false negative) and misinterpreted 4 malignant lesions as benign (interpretive error). Although it was not the purpose of this study to evaluate the use of ultrasound in expert hands, with a minimum follow-up period of two years, none of the patients have re-attended with a significant lesion. Discussion This is the first study to describe the process of an ENT trainee undertaking structured training in neck ultra- sound. Head and neck ultrasound is difficult, and fraught with pitfalls. Nevertheless, the radiologist in this study (LB) has trained numerous radiologists to a level consistent with non-specialist general radiology practice. The experience required to define or interpret some lesions may be measured in years rather than months, and this would apply equally to a radiologist or sonographer learning head and neck ultrasound. Surgeon-performed neck ultrasound is infrequently discussed in the literature, with most reports describing the value of peri-operative localisation of parathyroid lesions in shortening operation time. 6 – 8 Other studies focused on the advantage of clinic-based ultrasound in changing decisions about operative management of thyroid disease when compared to scans performed by a conventional ultrasound practitioner before the clinic visit. 9 Spurious lesions are frequent in head and neck ultrasound ( Table III ), commonly the result

TABLE IV TRAINEE FALSE NEGATIVES: PALPABLE LUMPS ∗

Pathology

Lesion missed by trainee

Source of error

Submandibular Submandibular

Stone

Scanning too quick

Sublingual ranula herniate thought mylohyoid muscle Trainee considered ranula a normal structure (muscle)

Parotid † Parotid Parotid Thyroid

Controls set to a deeper level ‡ Controls set to a deeper level ‡

Lipoma

Sebaceous cyst

Duct stricture with sialectasis

No comparison made to contralateral side (wider lumen)

Solid colloid inside large thyroid cyst

Failure to scan entire cyst

Anterior neck Anterior neck

Level III LN

Distraction by incidental adjacent thyroid nodule Inadequate knowledge of US features of a bony structure ∗∗

Prominent transverse process of vertebrae

Posterior triangle Thrombosed blood vessel Doppler scan was not used ∗ 10 patients. † n = 2. ‡ Lesion was in superficial skin layers. ∗∗ Appears as white line as it reflects sound. LN = lymph node; US = ultrasound

3

Made with