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

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

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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.

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