Faculty Bibliography

Introduction: Thyroid fine-needle aspiration (FNA) cytology combined with molecular testing guides individualized patient management by providing information regarding tumor biology and the risk of recurrence associated with specific mutations in the indeterminate groups (Bethesda group III-V). Thyroid adenomaassociated (THADA)-IGF2BP3 fusions have been identified as an oncogenic event in thyroid neoplasms, but the clinical-pathologic features and subsequent management are not well-established. Here we report the findings associated with thyroid nodules with THADA-IGFBP3 fusions in our institution.
Material(s) and Method(s): FNA cytology samples of thyroid nodules during 01/2015-12/2016 with the diagnosis of atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS; Bethesda III), follicular neoplasm/ suspicious for follicular neoplasm (FN/SFN; Bethesda IV) and suspicious for malignancy (Bethesda V) with corresponding ThyroSeqV2 data were assessed. Molecular test results yielding a THADA gene fusion were identified. In addition, follow-up surgical pathology and available radiology results were reviewed.
Result(s): 186 out of 558 (33.3%) thyroid nodules displayed molecular alterations; 7 out of 186 (3.8%) Bethesda category III-V nodules with ThyroSeq molecular alterations displayed isolated THADA-IGFBP2 fusions (Table 1). The median age was 45 years. The female to male ratio was 5:2. The nodule sizes ranged from 1.8 to 5.0 cm. Four (57%) patients had surgery; three cases displayed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) on histology; one case was a follicular adenoma. No patients had recurrence or metastasis on follow-up.
Conclusion(s): Our pilot study shows that thyroid nodules with THADA-IGF2BP3 fusions display low-risk/indolent features. These findings may aid in clinical management decisions in patients presenting with thyroid nodules with isolated THADAIGF2BP3 fusions on molecular testing

OBJECTIVES/HYPOTHESIS/OBJECTIVE:To create a model of the anatomic distribution, recurrence, and growth patterns of recurrent respiratory papillomatosis (RRP). STUDY DESIGN/METHODS:Prospective, multi-institutional cohort study. METHODS:Adult patients with a diagnosis of RRP evaluated between August 1, 2018 and February 1, 2021 at six participating centers were invited to enroll. At each office or operating room encounter, laryngologists recorded the location and size of RRP lesions using a 22-region schematic. A generalized linear mixed effects model was used to compare region variations in lesion prevalence and recurrence. RESULTS:The cohort comprised 121 patients: 74% were male, 81% had been diagnosed with adult-onset RRP, and a plurality (34%) had undergone 0 to 3 RRP interventions prior to enrollment. Across the study period, the odds of a lesion occurring in the glottis was significantly higher (odds ratio [OR]: 26.51; 95% confidence interval [CI]: 11.76-59.75, P < .001) compared with all other areas of the larynx and trachea. Within the true vocal folds, the membranous vocal folds had significantly higher odds (OR: 6.16; 95% CI: 2.66-14.30, P < .001) of lesion occurrence compared to the cartilaginous vocal folds. Despite these strong trends in lesion distribution, there were no differences in the odds of lesion recurrence, growth, or in the time to recurrence, between anatomic subsites. CONCLUSIONS:RRP lesions are most likely to occur in the glottis, particularly the membranous vocal folds, compared with other regions of the larynx or trachea. However, all lesions demonstrate similar behavior with respect to recurrence, growth, and time to recurrence regardless of anatomic location. LEVEL OF EVIDENCE/METHODS:3 Laryngoscope, 2022.

OBJECTIVE/UNASSIGNED:This study aimed to compare the historical incidence rate of severe oral mucositis (OM) in head and neck cancer patients undergoing definitive concurrent chemoradiation therapy (CRT) versus a prospective cohort of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with prophylactic photobiomodulation therapy (PBMT). METHODS/UNASSIGNED:This US-based, institutional, single-arm, phase Ⅱ prospective clinical trial was initiated in 50 patients (age ≥ 18 years, Karnofsky Performance Scale Index > 60, with locally advanced HNSCC (excluding oral cavity) receiving definitive or adjuvant radiation therapy (RT) with concurrent platinum-based chemotherapy (CT). PBMT was delivered three times per week throughout RT utilizing both an intraoral as well extraoral delivery system. Primary outcome measure was incidence of severe OM utilizing both the National Cancer Institute Common Toxicity Criteria, version 4.0 (NCI-CTCAE) Grade ≥3 and the World Health Organization Mucositis Grading Scale (WHO) Grade ≥3 versus historical controls; secondary outcome measures included time to onset of severe OM following therapy initiation. RESULTS/UNASSIGNED:, respectively. Severe OM was observed in 11 of 47 patients (23%, confidence interval: 12, 38). OM toxicity grade trended upward during treatment, reaching a maximum at 7 weeks (WHO: 1.8 vs. NCI-CTCAE: 1.7). Subsequently, OM grade returned to baseline 3 months following completion of RT. The mean time to onset of severe OM was (35 ± 12) days. The mean time to resolution of severe OM was (37 ± 37) days. CONCLUSIONS/UNASSIGNED:Compared to historical outcomes, PBMT aides in decreasing severe OM in patients with locally advanced HNSCC. PBMT represents a minimally invasive, prophylactic intervention to decrease OM as a major treatment-related side effect.

OBJECTIVE/UNASSIGNED:Evaluate rates of Advanced Bionics Ultra 3D/Ultra cochlear implant failure in the setting of a worldwide device recall and report surgical and auditory outcomes after revision. METHODS/UNASSIGNED:Retrospective chart review was performed for adult and pediatric patients implanted with at risk devices at our center from 2016 to 2020. Device failure rates, surgical, and auditory outcomes were recorded and analyzed. RESULTS/UNASSIGNED: = 0.95). DISCUSSION/UNASSIGNED:Patients with device failure due to this field action performed well after revision implantation. Patients with bilateral at-risk devices but evidence of unilateral failure may elect to undergo simultaneous empiric revision of the contralateral device. Three patients who elected to change device manufacturers on revision have variable results that require further investigation. CONCLUSIONS/UNASSIGNED:Patients requiring revision for a device field action overall perform well. At-risk devices continue to require monitoring as a growing number are likely to fail over time.

INTRODUCTION/BACKGROUND:Oral cancer patients suffer severe chronic and mechanically-induced pain at the site of the cancer. Our clinical experience is that oral cancer patients report new sensitivity to spicy foods. We hypothesized that in cancer patients, mechanical and chemical sensitivity would be greater when measured at the cancer site compared to a contralateral matched normal site. METHODS:We determined mechanical pain thresholds (MPT) on the right and left sides of the tongue of 11 healthy subjects, and at the cancer and contralateral matched normal site in 11 oral cancer patients in response to von Frey filaments in the range of 0.008 to 300 g (normally not reported as painful). We evaluated chemical sensitivity in 13 healthy subjects and seven cancer patients, who rated spiciness/pain on a visual analog scale in response to exposure to six paper strips impregnated with capsaicin (0-10 mM). RESULTS:Mechanical detection thresholds (MDT) were recorded for healthy subjects, but not MPTs. By contrast, MPTs were measured at the site of the cancer in oral cancer patients (7/11 patients). No MPTs were measured at the cancer patients' contralateral matched normal sites. Measured MPTs were correlated with patients' responses to the University of California Oral Cancer Pain Questionnaire. Capsaicin sensitivity at the site of the cancer was evident in cancer patients by a leftward shift of the cancer site capsaicin dose-response curve compared to that of the patient's contralateral matched normal site. We detected no difference in capsaicin sensitivity on the right and left sides of tongues of healthy subjects. CONCLUSIONS:Mechanical and chemical sensitivity testing was well tolerated by the majority of oral cancer patients. Sensitivity is greater at the site of the cancer than at a contralateral matched normal site.

OBJECTIVES/OBJECTIVE:) laser or microlaryngeal instruments (cold steel). This study compares the functional efficacy and safety of coblation, or "cold" radiofrequency ablation, to traditional approaches for endoscopic laryngeal cleft repair. METHODS:laser, cold steel, or coblator at two tertiary academic centers from 2015 to 2021 were retrospectively identified. The primary outcome studied was swallowing function: pre- and postoperative swallow studies were scored according to the International Dysphagia Diet Standardization Initiative with higher scores indicating worse swallow function. Secondary outcomes included surgical complications and rates of dehiscence. RESULTS:laser, 23 with cold steel, and 16 with the coblator. Mean age at surgery was 2.2 ± 1.1 years for the laser group, 4.3 ± 4.0 years for cold steel, and 1.9 ± 1.4 years for the coblator group. In the laser group, 100% of clefts were type I; for the cold steel group, 82.6% of clefts were type I and 17.4% were type II; for the coblator group, 93.8% of clefts were type I and 6.3% were type II. Pre- and postoperative swallow study scores were 6.3 ± 2.8 and 4.3 ± 3.2, respectively, (p = 0.001) for the laser group, 6.9 ± 2.8 and 5.3 ± 3.1 (p = 0.071) for the cold steel group, and 7.5 ± 1.5 and 4.0 ± 2.9 (p < 0.001) for the coblator group. Mean change in swallow study scores were similar across the three groups (p = 0.212). No patients experienced postoperative dehiscence at the surgical site or complications; no revisions were required. CONCLUSIONS:Cleft repair with the novel coblation technique showed significant improvements in swallow study scores without any occurrences of postoperative dehiscence or revisions. Coblation is a safe and efficacious approach for laryngeal cleft repair.

OBJECTIVE:Maximal safe resection is the goal of surgical treatment for high-grade glioma (HGG). Deep-seated hemispheric gliomas present a surgical challenge due to safety concerns and previously were often considered inoperable. The authors hypothesized that use of tubular retractors would allow resection of deep-seated gliomas with an acceptable safety profile. The purpose of this study was to describe surgical outcomes and survival data after resection of deep-seated HGG with stereotactically placed tubular retractors, as well as to discuss the technical advances that enable such procedures. METHODS:This is a retrospective review of 20 consecutive patients who underwent 22 resections of deep-seated hemispheric HGG with the Viewsite Brain Access System by a single surgeon. Patient demographics, survival, tumor characteristics, extent of resection (EOR), and neurological outcomes were recorded. Cannulation trajectories and planned resection volumes depended on the relative location of white matter tracts extracted from diffusion tractography. The surgical plans were designed on the Brainlab system and preoperatively visualized on the Surgical Theater virtual reality SNAP platform. Volumetric assessment of EOR was obtained on the Brainlab platform and confirmed by a board-certified neuroradiologist. RESULTS:Twenty adult patients (18 with IDH-wild-type glioblastomas and 2 with IDH-mutant grade IV astrocytomas) and 22 surgeries were included in the study. The cohort included both newly diagnosed (n = 17; 77%) and recurrent (n = 5; 23%) tumors. Most tumors (64%) abutted the ventricular system. The average preoperative and postoperative tumor volumes measured 33.1 ± 5.3 cm3 and 15.2 ± 5.1 cm3, respectively. The median EOR was 93%. Surgical complications included 2 patients (10%) who developed entrapment of the temporal horn, necessitating placement of a ventriculoperitoneal shunt; 1 patient (5%) who suffered a wound infection and pulmonary embolus; and 1 patient (5%) who developed pneumonia. In 2 cases (9%) patients developed new permanent visual field deficits, and in 5 cases (23%) patients experienced worsening of preoperative deficits. Preoperative neurological or cognitive deficits remained the same in 9 cases (41%) and improved in 7 (32%). The median overall survival was 14.4 months in all patients (n = 20) and in the newly diagnosed IDH-wild-type glioblastoma group (n = 16). CONCLUSIONS:Deep-seated HGGs, which are surgically challenging and frequently considered inoperable, are amenable to resection through tubular retractors, with an acceptable safety profile. Such cytoreductive surgery may allow these patients to experience an overall survival comparable to those with more superficial tumors.

Purpose/Objective(s): HNSCS is a rare diagnosis with an overall poor prognosis. Due to its rarity, our understanding of HNSCS and its optimal management is mainly derived from retrospective and single-institution studies. We aimed to evaluate the disease characteristics, patterns of care, and survival outcomes in patients with HNSCS. Materials/Methods: Using the National Cancer Database (NC

Liquid biopsy has emerged as a novel noninvasive tool in cancer diagnostics. While significant strides have been made in other malignancies using liquid biopsy for diagnosis, disease monitoring, and treatment selection, development of these assays has been more challenging for brain tumors. Recently, research in primary and metastatic brain tumors has begun to harness the potential utility of liquid biopsy-particularly using circulating tumor DNA (ctDNA). Initial studies to identify ctDNA in plasma of brain tumor patients have shown feasibility, but the yield of ctDNA is far below that for other malignancies. Attention has therefore turned to the cerebrospinal fluid (CSF) as a more robust source of ctDNA. This review discusses the unique considerations in liquid biopsy for glioma and places them in the context of the work to date. We address the utility of CSF liquid biopsy for diagnosis, longitudinal monitoring, tracking tumor evolution, clinical trial eligibility, and prognostication. We discuss the differences in assay requirements for each clinical application to best optimize factors such as efficacy, cost, and speed. Ultimately, CSF liquid biopsy has the potential to transform how we manage primary brain tumor patients.