Faculty Bibliography

Management of head and neck squamous cell carcinoma necessitates a multimodal approach. The neck dissection has evolved over many years but is well established as the key surgical intervention for management of nodal disease in the neck. The open neck dissection has many varieties based on location and degree of disease but is the gold standard surgical technique. Robot-assisted neck dissections have emerged in recent years as an alternative. More research is required to establish long-term oncologic outcomes achieved with robot-assisted surgery and to assess whether cost and operative times decrease with experience.

PURPOSE:Understanding the role of transoral surgery in oropharyngeal cancer (OPC) requires prospective, randomized multi-institutional data. Meticulous evaluation of surgeon expertise and surgical quality assurance (QA) will be critical to the validity of such trials. We describe a novel surgeon credentialing and QA process developed to support the ECOG-ACRIN Cancer Research Group E3311 (E3311) and report outcomes related to QA. PATIENTS AND METHODS:E3311 was a phase II randomized clinical trial of transoral surgery followed by low- or standard-dose, risk-adjusted post-operative therapy with stage III-IVa (AJCC 7th edition) HPV-associated OPC. In order to be credentialed to accrue to this trial, surgeons were required to demonstrate active hospital credentials and technique-specific surgical expertise with ≥20 cases of transoral resection for OPC. In addition, 10 paired operative and surgical pathology reports from the preceding 24 months were reviewed by an expert panel. Ongoing QA required <10% rate of positive margins, low oropharyngeal bleeding rates, and accrual of at least one patient per 12 months. Otherwise surgeons were placed on hold and not permitted to accrue until re-credentialed using a new series of transoral resections. RESULTS:120 surgeons trained in transoral minimally invasive surgery applied for credentialing for E3311 and after peer-review, 87 (73%) were approved from 59 centers. During QA on E3311, positive final pathologic margins were reported in 19 (3.8%) patients. Grade III/IV and grade V oropharyngeal bleeding was reported in 29 (5.9%) and 1 (0.2%) of patients. CONCLUSIONS:We provide proof of concept that a comprehensive credentialing process can support multicenter transoral head and neck surgical oncology trials, with low incidence of positive margins and *grade III/V oropharyngeal bleeding.

PURPOSE:To provide evidence-based recommendations to practicing physicians and other health care providers on the diagnosis and management of squamous cell carcinoma of unknown primary in the head and neck (SCCUP). METHODS:The American Society of Clinical Oncology convened an Expert Panel of medical oncology, surgery, radiation oncology, radiology, pathology, and advocacy experts to conduct a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 2008 through 2019. Outcomes of interest included survival, local and regional disease control, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS:The literature search identified 100 relevant studies to inform the evidence base for this guideline. Four main clinical questions were addressed, which included subquestions on preoperative evaluations, surgical diagnostic and therapeutic procedures, appropriate pathology techniques, and adjuvant therapy. RECOMMENDATIONS:Evidence-based recommendations were developed to address preoperative evaluation for patients with a neck mass, surgical diagnostic and therapeutic procedures, appropriate treatment options in unilateral versus bilateral SCCUP.Additional information is available at www.asco.org/head-neck-cancer-guidelines.

The COVID-19 pandemic has created uncertainty regarding the safety and appropriate utilization of minimally invasive surgery (MIS) during this current outbreak. Surgical governing bodies such as Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) and the Royal Colleges of Surgery of Great Britain and Ireland have made statements regarding the possibility of COVID-19 release into CO2 insufflant during MIS. The basis for this concern is prior evidence in the literature of other viral pathogen release during laparoscopic surgery. The recommendations are correctly based on caution given the lack of understanding of how COVID-19 compares to other viruses with regard to transmission and presence in CO2 during MIS. In this review we have investigated the available literature on COVID-19 transmission during MIS, address the implications of current and previously published recommendations and discuss steps to mitigate COVID-19 transmission during MIS for staff and patient safety.

Cetuximab, an anti-EGFR monoclonal antibody (mAb), is approved for advanced head and neck squamous cell carcinoma (HNSCC) but benefits a minority. An established tumor-intrinsic resistance mechanism is cross-talk between the EGFR and hepatocyte growth factor (HGF)/cMet pathways. Dual pathway inhibition may overcome cetuximab resistance. This Phase I study evaluated the combination of cetuximab and ficlatuzumab, an anti-HGF mAb, in patients with recurrent/metastatic HNSCC. The primary objective was to establish the recommended Phase II dose (RP2D). Secondary objectives included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Mechanistic tumor-intrinsic and immune biomarkers were explored. Thirteen patients enrolled with no dose-limiting toxicities observed at any dose tier. Three evaluable patients were treated at Tier 1 and nine at Tier 2, which was determined to be the RP2D (cetuximab 500 mg/m² and ficlatuzumab 20 mg/kg every 2 weeks). Median PFS and OS were 5.4 (90% CI = 1.9-11.4) and 8.9 (90% CI = 2.7-15.2) months, respectively, with a confirmed ORR of 2 of 12 (17%; 90% CI = 6-40%). High circulating soluble cMet levels correlated with poor survival. An increase in peripheral T cells, particularly the CD8⁺ subset, was associated with treatment response whereas progression was associated with expansion of a distinct myeloid population. This well-tolerated combination demonstrated promising activity in cetuximab-resistant, advanced HNSCC.

The 2019 novel coronavirus (COVID-19) pandemic has created significant challenges to the delivery of care for patients with advanced head and neck cancer requiring multimodality therapy. Performing major head and neck ablative surgery and reconstruction is a particular concern given the extended duration and aerosolizing nature of these cases. In this manuscript, we describe our surgical approach to provide timely reconstructive care and minimize infectious risk to the providers, patients, and families.

BACKGROUND AND PURPOSE:The Neck Imaging Reporting and Data System is a standardized reporting system intended to risk stratify patients treated for head and neck squamous cell carcinoma. The purpose of this study is to investigate the positive predictive value of the Neck Imaging Reporting and Data System categories 3 and 4 on posttreatment PET/CT in patients treated definitively for head and neck squamous cell carcinoma. MATERIALS AND METHODS:We retrospectively identified patients treated definitively for head and neck squamous cell carcinoma between 2006 and 2018. Patients whose posttreatment PET/CT scans were interpreted as Neck Imaging Reporting and Data System 3 (suspicious) or 4 (definitive recurrence) at the primary site, regional nodes, or at distant sites were included. The reference standard was histopathology or unequivocal imaging or clinical evidence of treatment failure. The positive predictive values of Neck Imaging Reporting and Data System 3 and 4 posttreatment PET/CT were calculated. RESULTS:Seventy-two of 128 patients with posttreatment PET/CT interpreted as Neck Imaging Reporting and Data System 3 at the primary site, regional nodes, or distant sites were proved to have treatment failure at the suspicious sites, yielding an overall positive predictive value of 56% (95% CI, 48%-65%). The positive predictive values of Neck Imaging Reporting and Data System 3 by subsite were as follows: primary site, 56% (44/79); regional nodes, 65% (34/52); and distant sites, 79% (42/53). All 69 patients with posttreatment PET/CT interpreted as Neck Imaging Reporting and Data System 4 had true treatment failure, yielding a positive predictive value of 100% (95% CI, 96%-100%): primary site, 100% (28/28); regional nodes, 100% (32/32); and distant sites, 100% (29/29). CONCLUSIONS:The positive predictive value of Neck Imaging Reporting and Data System 3 on posttreatment PET/CT is relatively low. Thus, Neck Imaging Reporting and Data System 3 findings should be confirmed with tissue sampling before instituting new salvage treatment regimens to avoid unnecessary overtreatment and its associated toxicities. Neck Imaging Reporting and Data System 4 reliably indicates recurrent disease.

Multidisciplinary conferences (MDC) are an important component of head and neck oncologic care including diagnosis, treatment, and survivorship. Virtual MDC allows for improved collaboration between providers at distant sites and proper allocation of health care resources in a time of crisis. When approached systematically, a virtual MDC is feasible to design and implement in a large academic medical center with multiple satellite hospitals.

Knowledge of the genetic landscape of aggressive well differentiated thyroid cancers (WDTC) is lacking. Retrospective review of institutional database was performed to identify locally-invasive thyroid carcinomas and a comparison cohort of low-risk WDTC. ThyroSeq v2 next-generation sequencing was performed on available tissue. Survival time was analyzed by Kaplan-Meier methods and compared between groups via the log-rank test. Time to recurrence, treating death as a competing risk, was analyzed by cumulative incidence and compared between groups. Of 80 T4 tumors, 29 (36%) were met inclusion criteria, of which, 25 had genetic and clinicopathologic data. Most (24/25, 96%) harbored at least one genetic alteration, most commonly BRAF V600E (19, 76%), followed by mutations in the promoter region of TERT (14, 56%). Co-occurrence of BRAF and TERT was identified in 12 (48%) and associated with significantly higher risk of recurrence (p < 0.05). Conversely, co-occurrence of BRAF and TERT was present in only 5 of 102 (5%) patients presenting with early-stage WDTC. Compared to early-stage WDTC, co-occurrence of BRAF and TERT mutations are common in locally advanced (T4) thyroid cancer and are associated with an increased risk of recurrence. This knowledge may help predict aggressive behavior pretreatment and inform perioperative decision-making.