American Head & Neck Society

Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.

Published on by Stephen Lai

NRG-HN006 Trial

Sentinel Lymph Node Biopsy versus Elective Neck Dissection for Early-Stage Oral Cavity Cancer: Activation of the NRG-HN006 Trial

For patients with early-stage oral cavity squamous cell carcinoma (OCSCC), there is a 20-30% risk for occult metastatic cervical disease despite clinical and radiographic ima Tirging. The debate surrounding management of the node-negative neck has spanned multiple decades initially centered around elective neck dissection (END) versus “watchful waiting” with subsequent therapeutic neck dissection. Recently, sentinel lymph node biopsy (SLN Bx) has emerged as a viable option for active management of the node-negative neck in these patients.

NRG Oncology has just activated a National Cancer Institute (NCI)-approved international, multi-institutional prospective trial comparing SLN Bx versus END for early-stage oral cavity cancer. The study is NRG-HN006 “Randomized Phase II/III Trial of Sentinel Lymph Node Biopsy Versus Elective Neck Dissection for Early-Stage Oral Cavity Cancer.” (Clinicaltrials.gov: NCT04333537)

The trial divides patients to two surgical arms, SLN Bx and END, following a PET/CT scan with a central reading as an integral biomarker supported by the NCI. The trial builds upon the recent results of the ACRIN 6685 trial, which demonstrated the relatively high negative predictive value of PET/CT for neck disease in patients with T2-4N0 head and neck cancers. Patients with a positive central read of their PET/CT for neck disease will still have their neck pathology results recorded to understand the functional performance of PET/CT in accurately assessing neck nodal status.

Patients with a negative central read of their PET/CT for neck disease will be randomized to the two surgical arms with stratification based on T-stage and performance status (Zubrod). The Phase II portion of the trial will test the hypothesis that SLN biopsy will have superior patient-reported neck and shoulder function and quality of life (QOL), as measured by the Neck Dissection Impairment Index (NDII), compared to END at 6 months post-surgery. Comparing the difference in the two arms from baseline and 6 months will serve to determine the “Go/No-Go” decision to proceed to Phase III. Phase III has co-primary endpoints and will test the hypothesis that SLN Bx will achieve non-inferior disease-free survival (DFS) compared to END, and that SLN Bx will have superior patient-reported neck and shoulder function and QOL, as measured by the NDII.

NRG-HN006 has an ambitious patient accrual target of 224 patients for Phase II who will be included as part of the 618 patients total for Phase III. The trial represents an opportunity to address the performance of SLN Bx and END in a definitive manner relative to QOL and patient survival. The collection of high-quality prospective data in this study will also permit the assessment of issues that continue to be raised with regard to extent of treatment for early-stage OCSCC, including extent of END, distribution of occult metastatic disease, and practice variations in adjuvant radiation therapy.

Site activation is currently in process and additional details, including the complete protocol, can be obtained here: CTSU website. Surgeon credentialing will require completion of an education course and case review. Please feel free to contact the study PI at [email protected] if you have additional questions and/or issues.

 

 

Published on by AHNS Administrative Office

AHNS Journal Club – July 2020

Volume 32 – July, 2020

The AHNS Journal Club reviews the leading head and neck cancer-related journals, sharing with AHNS members some of the most relevant and important manuscripts, and providing summaries and critiques of the work.

The Journal Club for the July issue: AHNS Skull Base Surgery Edition

This Issue of the AHNS Journal Club has been compiled and reviewed by members of the

AHNS Skull Base Surgery Section (Ivan El-Sayed, Chair; Ian Witterick, Co-Chair)

 Meghan Turner
Marilene Wang
Shirley Su
Harishanker Jeyarajan

Dear Colleagues,

The AHNS Skull Base Surgery Section is very pleased to present its first AHNS Journal Club Issue.  Our ultimate goal for the Skull Base Surgery Section issues will be to provide insight into contemporary management of skull base tumors through themed issues.  This particular issue will address controversies in the recently published literature on nodal metastases in olfactory neuroblastoma (ONB) by reviewing the recently published literature.

Traditionally, elective treatment of cervical nodal metastases for head and neck primaries is advocated when the risk of occult metastases reaches > 20%.  However, sinonasal malignancy (as a group) has been shown to have a lower incidence of cervical metastases on presentation making elective treatment of the neck in sinonasal malignancy controversial and somewhat rare. With respect to ONB, the incidence of nodal metastases at the time of diagnosis (modified Kadish stage D) is low, approximately 8%.1,2  In spite of this rare incidence at diagnosis, up to 20.2% of patients with ONB will develop nodal disease within 5 years of diagnosis.3

Single institution studies have tried to identify risk factors for nodal recurrence (positive margins, modified Kadish C Staging, Hyam’s grade, the presence of dural invasion) and identify patients who might benefit from elective treatment of the neck.4-6  This has led to more recent studies examining elective treatment of high-risk nodal basins including retropharyngeal, level IB and level II lymph nodes.7  Elective neck irradiation provides 100% locoregional control in small, single-institution series, but was associated with worse overall survival in patients over 50.  Salvage treatment of the delayed nodal recurrence has 5-year LRC rates of 30-80% and is highest when both surgery and radiation are used.3,6  It remains unclear whether or not elective treatment of the neck reduces distant metastasis or has meaningful impact on survival as metastases are largely found in the brain, leptomeningeal spine, or the spinal skeleton.6,7

In this issue, we present recent evidence regarding nodal metastases in ONB.  It is suggested you read them in the order presented.  We believe this evidence may impact future trends in the treatment of ENB and hope you enjoy this issue.  Comments are welcome and can be sent to [email protected].

Sincerely,

Meghan T. Turner, MD
Assistant Professor of Head and Neck Surgery
West Virginia University Health Sciences Center

Marilene Wang, MD
Professor of Head and Neck Surgery
Ronald Reagan UCLA Medical Center

Harishanker Jeyarajan, MD
Assistant Professor of Head and Neck Surgery
University of Alabama Birmingham School of Medicine

Shirley Y. Su, MBBS
Associate Professor of Head and Neck Surgery
Associate Professor of Neurosurgery
The University of Texas M.D. Anderson Cancer Center

  1. Kuan EC, Nasser HB, Carey RMet al. A Population-Based Analysis of Nodal Metastases in Esthesioneuroblastomas of the Sinonasal Tract. Laryngoscope 2019; 129:1025-1029.
  2. Konuthula N, Iloreta AM, Miles Bet al. Prognostic significance of Kadish staging in esthesioneuroblastoma: An analysis of the National Cancer Database. Head Neck 2017; 39:1962-1968.
  3. Gore MR, Zanation AM. Salvage treatment of late neck metastasis in esthesioneuroblastoma: a meta-analysis. Arch Otolaryngol Head Neck Surg 2009; 135:1030-1034.
  4. Marinelli JP, Janus JR, Van Gompel JJet al. Dural Invasion Predicts the Laterality and Development of Neck Metastases in Esthesioneuroblastoma. J Neurol Surg B Skull Base 2018; 79:495-500.
  5. Nalavenkata SB, Sacks R, Adappa NDet al. Olfactory Neuroblastoma: Fate of the Neck–A Long-term Multicenter Retrospective Study. Otolaryngol Head Neck Surg 2016; 154:383-389.
  6. Banuchi VE, Dooley L, Lee NYet al. Patterns of regional and distant metastasis in esthesioneuroblastoma. Laryngoscope 2016; 126:1556-1561.
  7. Jiang W, Mohamed ASR, Fuller CDet al. The role of elective nodal irradiation for esthesioneuroblastoma patients with clinically negative neck. Pract Radiat Oncol 2016; 6:241-247.

CLICK THE ARTICLES BELOW TO ACCESS THE CURRENT ISSUE

Patterns of Regional and Distant Metastasis in Esthesioneuroblastoma

Victoria E Banuchi, MD Laura Dooley, MD, Nancy Y Lee, MD, David G. Pfister, Sean McBride, MD MPH, Nadeem Riaz, MD, Mark H Bilsky, MD, Ian Ganly, MD, Jatin P Shah, MD, Dennis H Kraus, MD, and Luc GT Morris, MD MSc
From The Laryngoscope, July 2016

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A Population-Based Analysis of Nodal Metastases in Esthesioneuroblastomas of the Sinonasal Tract
Edward C Kuan, Hassan B Nasser, Ryan M Carey, Alan D Workman, Jose E Alonso, Marilene B Wang, Maie A St John, James N Palmer, Nithin D Adappa, Bobby A Tajudeen
 From The Laryngoscope, May 2019

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The Role of Elective Nodal Irradiation for Esthesioneuroblastoma Patients with Clinically Negative Neck
Wen Jiang, Abdallah S R Mohamed , Clifton David Fuller, Betty Y S Kim, Chad Tang , G Brandon Gunn, Ehab Y Hanna, Steven J Frank, Shirley Y Su, Eduardo Diaz, Michael E Kupferman, Beth M Beadle, William H Morrison, Heath Skinner, Stephen Y Lai , Adel K El-Naggar, Franco DeMonte, David I Rosenthal, Adam S Garden, Jack Phan 

From the Practical Radiation Oncology, July-August 2016

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Olfactory Neuroblastoma: Fate of the Neck–A Long-term Multicenter Retrospective Study

Sunny B Nalavenkata, Raymond Sacks, Nithin D Adappa, James N Palmer, Michael T Purkey, Michael D Feldman, Rodney J Schlosser, Carl H Snyderman, Eric W Wang, Bradford A Woodworth, Robert Smee, Thomas E Havas, Richard Gallagher, Richard J Harvey
From the Otolaryngology and head and neck surgery, February 2016

From the Practical Radiation Oncology, July-August 2016

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Neck Recurrence and Mortality in Esthesioneuroblastoma: Implications for Management of the NO Neck

James G Naples , Jeffrey Spiro, Belachew Tessema, Clinton Kuwada, Chia-Ling Kuo, Seth M Brown

From The Laryngoscope, June 2016

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Dural Invasion Predicts the Laterality and Development of Neck Metastases in Esthesioneuroblastoma

John P Marinelli, Jeffrey R Janus, Jamie J Van Gompel, Michael J Link, Eric J Moore, Kathryn M Van Abe, Brandon W Peck, Christine M Lohse, Daniel L Price

From the Journal of neurological surgery. Part B, Skull Base, October 2018.

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Olfactory Neuroblastoma: Fate of the Neck–A Long-term Multicenter Retrospective Study
Sunny B Nalavenkata, Raymond Sacks, Nithin D Adappa, James N Palmer, Michael T Purkey, Michael D Feldman, Rodney J Schlosser, Carl H Snyderman, Eric W Wang, Bradford A Woodworth, Robert Smee, Thomas E Havas, Richard Gallagher, Richard J Harvey

From the Otolaryngology and head and neck surgery, February 2016

Published on by Natalie Silver

AHNS Basic Science/Translational Newsletter Vol 3

Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomized trial

Anthony C Nichols, Julie Theurer, Eitan Prisman, Nancy Read, Eric Berthelet….David A Palma

From Clinical Trial. The Lancet. Oncology, October 2019; 20(10):1349-1359.

Article Review by Natalie Silver, MD

Background/Hypothesis:

Design: Investigator-initiated, multicenter, international, open label, parallel-group, phase 2, randomized clinical trial comparing T1-T2, N0-2 OPSCC patients randomized to either primary radiotherapy (70Gy, chemotherapy if N1-N2) or TORS plus neck dissection (with/without pathologic based adjuvant chemo/radiotherapy). The primary endpoint was swallowing-related QOL at 1 year as established by the MD Anderson Dysphagia Inventory (MDADI) score, powered to detect a 10 point improvement (a clinically meaningful change).

Summary of results: 68 patients (34 per group) were randomized over a 5 year period (following stratification by p16 status). MDADI total scores at 1 year were: mean 86.9 (SD 11.4) in the radiotherapy (RT) group and 80.1 (SD 13.0) in the TORS plus neck dissection group (p=0.042), which did not meet the prescribed threshold (10 points) for a clinically meaningful difference. Toxicity patterns differed between the two groups with neutropenia, hearing loss and tinnitus being more common in the in the RT group and more cases of trismus in the TORS plus neck dissection group. The most common adverse events in the RT group were dysphagia (n=6), hearing loss (n-6), and mucositis (n=4) and in the TORS plus neck dissection group, dysphagia was the most common adverse event (n=9) and there was one patient death caused by bleeding after TORS. Oncologic outcomes were similar in both groups.

Strengths:

  • Well-designed, prospective randomized clinical trial..
  • Highest level of evidence for a clinical study (Level I evidence).
  • Multi-institutional and international trial.which was not measured in this study.
  • MDADI is a commonly used and validated swallowing QOL assessment tool.

 Weaknesses

  • Modest sample size and was not powered to compare survival outcomes.
  • Institutional differences in criteria for administration of adjuvant therapy may be confounding.
  • Radiotherapy has late side effects, specifically with respect to dysphagia and the swallowing QOL scores may worsen more considerably in the radiotherapy group >1 year after treatment,  which was not measured in this study.

Key Points:

  • While this study did not show clinically meaningful differences in swallowing QOL scores at 1 year, this is the only prospective randomized controlled clinical trial published, to date, to address this concern.
  • Tese findings conflict with previous non-randomized comparisons of radiotherapy with TORS which have found that both modalities achieved similar oncologic outcomes, but that functional outcomes appeared better with TORS (Yeh et al, systematic review 2015).
  • Much of the QOL data (not only swallowing data) in this study favored radiotherapy. The surgical group had a clinically meaningful decline in scores for “Global” (p=0.024) and “Emotional” (p=0.021) subscales. These differences (when compared to retrospective studies) may be due to bias in the retrospective reviews that included advanced T –stage patients not amenable to TORS, or early studies prior to IMRT.
  • In a multidisciplinary setting, it is important for clinicians to understand and counsel our patients in both surgical and non-surgical treatment options, since there are differences in risks and toxicity patterns for the two treatment modalities. Studies, like ORATOR, may be used as a guide, but additional clinical research is needed and discussions about treatment options should be personalized to each individual patient and institution.
  • The results from several more clinical trials will provide high quality evidence for outstanding questions that can help guide us to tailor treatment for OPSCC patients, these include; the QoLATI trial (with similar cohorts and endpoints to ORATOR), ECOG 3311 (NCT01898494) and the ORATOR2 trial (NCT03210103).

From the Basic Science/Translational Service
Jeffrey C. Liu MD Vice Chair
Richard Wong MD Chair

Natalie Silver

Natalie Silver

Natalie Silver MD, MS, FACS is an Assistant Professor in the Department of Otolaryngology, Head and Neck Surgery, Division of Surgical Oncology, at the University of Florida. She is the UFHealth Cancer Center Head and Neck Cancer Disease Site Group Research Leader. Dr. Silver has an active clinical practice treating head and neck cancer patients. She is also PI of a translational research lab focused on developing therapeutic oral cancer vaccines and investigating the role of the microbiome in the development and progression of oral cancer.
Natalie Silver

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Published on by Cherie-Ann Nathan

AHNS Endorses ACS Statement on Recent Violence and Protests

Dear AHNS Member,

The American Head and Neck Society (AHNS) strongly endorses the below statement from the American Colleges of Surgeons (ACS) regarding the recent violence and protests. Please join us in supporting the ACS and please stay safe and well. Thank you.

Cherie-Ann Nathan, MD
AHNS President

 

American College of Surgeons Response To Recent Violence and Protests

Recent events across the country have significantly impacted us all, particularly Fellows who are members of Black and Brown communities.

The ACS stands in solidarity against racism, violence, and intolerance. Our mission is to serve all with skill and fidelity, and that extends beyond the operating room.

Racism, brutal attacks, and subsequent violence must end. We will help any injured, and we will use our voice in support of the health and safety of every person.

Cherie-Ann Nathan

Cherie-Ann Nathan

Dr. Cherie-Ann Nathan is a leading head and neck cancer surgeon. She is Prof. & Chair of the Dept. of Oto/HNS &the Director of Head and Neck Surgical Oncology and Cancer Research, Feist-Weiller Cancer Center Louisiana State University Health - Shreveport (LSU Health Shreveport). The National Cancer Institute has funded her translational research since 2000 and her focus is on targeted therapy for head and neck patients. Dr. Nathan is recognized nationally and internationally for her seminal work on molecular analysis of surgical margins. She has pioneered multi-institutional clinical trials using mTOR inhibitors in HNSCC patients. She has also received NIH funding for chemoprevention of cancer with curcumin and has a patent for a curcumin chewing gum. More recently she also received an NCI grant on cutaneous Squamous cell cancer.  She serves on the NCI head and neck steering committee and the American Cancer Society HPV steering committee. Dr. Nathan has published extensively, has over 180 publications in peer-reviewed journals, and has authored multiple textbooks and encyclopedia chapters. She is married to Dr. Raghu Nathan, a pulmonary and critical eye care specialist with whom she has two boys.
Cherie-Ann Nathan

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Published on by Cherie-Ann Nathan

New AHNS COVID-19 Offering on AHNS Web Site

Dear AHNS Members,

The AHNS Education Division has helped create a valuable resource for our members to connect during the pandemic. The AHNS COVID-19 Forum can be accessed through your member account on the AHNS Web Site. Just log onto your account through www.ahns.info and go to the member dashboard to access the AHNS COVID-19 Forum. This was established as a quick way for our members to post questions, comments and suggestions in relation to the COVID-19 pandemic. This forum is only accessible to AHNS members. Posting in any forum subscribes you to that topic and you will receive email notifications of future posts. You may also subscribe to any topic or entire forums by locating the subscribe link.  Clicking your name on any forum page will allow you to modify your personal settings for the forum system. Please note that the views and comments expressed on the forum are views and opinions of those posting and not official AHNS viewpoints.

Please also visit the AHNS COVID-19 Bulletin Board, which serves as a platform on our website where members can share vetted information relevant to dealing with the COVID-19 pandemic. Please visit https://www.ahns.info/covid-19-info/ to view the bulletin board and also submit information. New information has been posted weekly.

And don’t forget to view one of the pieces that was added to the Bulletin Board, the AHNS COVID-19 Practice Patterns.  A direct link can be found here:

https://www.ahns.info/covid-19-info/covid_pp_spreadsheet/

This document is created by a set of head and neck surgeons who will post regular and ‘real-time’ updates about practice patterns, policy changes, and patient care considerations. These will be updated on a weekly basis at minimum, and more frequently if policies and patterns are changing more rapidly.

In addition, aggregate information previously collected from other institutions will be available to view.

We welcome your contributions. We are actively looking for contributors, as well as ideas for additional questions our institutions can help answer. New questions will be added and answered as soon as possible.

Please send any interest or correspondence regarding AHNS COVID-19 Practice Patterns to
[email protected]. 

I continue to be amazed at the great work our members are producing during this difficult time.
Thank you, again, for your service to the society and our specialty!

Cherie-Ann Nathan, MD
AHNS President

Cherie-Ann Nathan

Cherie-Ann Nathan

Dr. Cherie-Ann Nathan is a leading head and neck cancer surgeon. She is Prof. & Chair of the Dept. of Oto/HNS &the Director of Head and Neck Surgical Oncology and Cancer Research, Feist-Weiller Cancer Center Louisiana State University Health - Shreveport (LSU Health Shreveport). The National Cancer Institute has funded her translational research since 2000 and her focus is on targeted therapy for head and neck patients. Dr. Nathan is recognized nationally and internationally for her seminal work on molecular analysis of surgical margins. She has pioneered multi-institutional clinical trials using mTOR inhibitors in HNSCC patients. She has also received NIH funding for chemoprevention of cancer with curcumin and has a patent for a curcumin chewing gum. More recently she also received an NCI grant on cutaneous Squamous cell cancer.  She serves on the NCI head and neck steering committee and the American Cancer Society HPV steering committee. Dr. Nathan has published extensively, has over 180 publications in peer-reviewed journals, and has authored multiple textbooks and encyclopedia chapters. She is married to Dr. Raghu Nathan, a pulmonary and critical eye care specialist with whom she has two boys.
Cherie-Ann Nathan

Latest posts by Cherie-Ann Nathan (see all)