Cecelia E. Schmalbach

Safety and Tumor-specificity of Cetuximab-IRDye800 for Surgical Navigation in Head and Neck Cancer

Purpose: Positive margins dominate clinical outcomes after surgical resections in most solid cancer types, including head and neck squamous cell carcinoma. Unfortunately, surgeons remove cancer in the same manner they have for a century with complete dependence on subjective tissue changes to identify cancer in the operating room. To effect change, we hypothesize that EGFR can be targeted for safe and specific real-time localization of cancer. Experimental Design: A dose escalation study of cetuximab conjugated to IRDye800 was performed in patients (n = 12) undergoing surgical resection of squamous cell carcinoma arising in the head and neck. Safety and pharmacokinetic data were obtained out to 30 days after infusion. Multi-instrument fluorescence imaging was performed in the operating room and in surgical pathology. Results: There were no grade 2 or higher adverse events attributable to cetuximab-IRDye800. Fluorescence imaging with an intraoperative, wide-field device successfully differentiated tumor from normal tissue during resection with an average tumor-to-background ratio of 5.2 in the highest dose range. Optical imaging identified opportunity for more precise identification of tumor during the surgical procedure and during the pathologic analysis of tissues ex vivo. Fluorescence levels positively correlated with EGFR levels. Conclusions: We demonstrate for the first time that commercially available antibodies can be fluorescently labeled and safely administered to humans to identify cancer with sub-millimeter resolution, which has the potential to improve outcomes in clinical oncology. Clin Cancer Res; 21(16); 3658–66. ©2015 AACR.

Utility of Head and Neck Cutaneous Squamous Cell Carcinoma Sentinel Node Biopsy A Systematic Review

Objective Sentinel lymph node biopsy (SLNB) is standard of care for melanoma, but its role in cutaneous squamous cell carcinoma (cSCC) has not been established. Study objectives include: (1) analyze the feasibility and reliability SLNB for head and neck (H&N) cSCC and (2) identify risk factors associated with a positive SLN. Data Sources MEDLINE, PubMed, Cochrane, and ASCO databases searches conducted (1946-2013). Review Methods Using the PRISM model, a comprehensive systematic review of H&N cSCC SLNB studies with associated recurrence rates was conducted. Dual-blinded data extraction identify primary outcomes (successful SLN harvest and false omission rate) and secondary outcomes (risk factors associated with a +SLN). Results Two hundred twenty-one articles were screened; 73 patients from 11 publications met inclusion criteria (3 case series; 8 prospective cohorts). Studies ranged from 1 to 15 patients (median 5). Median age was 74 years. Median follow-up was 21.5 months. Average tumor size was 3.09 cm. At least 1 SLN was identified in 100% of patients (median 2). Ten (13.5%) had a positive SLN; no additional metastatic nodes were identified in 9 patients receiving completion lymphadenectomy. Tumor diameter was not associated with SLN status (P = .09; 95% CI, –.27 to 3.02). Risk factors (tumor depth, perineural invasion, location, differentiation) were not consistently recorded. Three of 63 (4.76%) failed regionally following a negative SLNB. Conclusion H&N cSCC SLNB is feasible and reliable for staging, with a false omission rate of 4.7% mirroring melanoma. Prospective studies documenting high risk features are required to further define its role.

Variables predictive of bilateral occult papillary microcarcinoma following total thyroidectomy.

Objective. To investigate risk factors associated with papillary thyroid microcarcinoma (PTM) involving the thyroid lobes bilaterally at the time of diagnosis. In doing so, the authors hope to identify a subset of PTM patients who may benefit from more aggressive surgical intervention with a total thyroidectomy. Study Design. A prospective cohort study of all newly diagnosed, previously untreated PTM patients presenting between 1998 and 2008. Setting. Tertiary care military hospital. Subjects and Methods. Following total thyroidectomy, patients were grouped according to unilateral versus bilateral PTM thyroid lobe involvement. The primary outcome variable was PTM in both thyroid lobes. Independent variables of interest included patient demographics, tumor stage, nodule size, tumor focus size, and tumor focality. Univariate analysis was used to investigate risk factors associated with bilateral lobe PTM. Results. Five of 25 (20%) patients had bilateral thyroid lobe PTM at presentation. There was no statistically significant difference between the unilateral versus bilateral groups with respect to age, gender, history, stage, and tumor size. Bilateral thyroid lobe PTM occurred significantly more often in the setting of multifocal PTM (4/7, 57%) versus unifocal PTM (1/18 cases, 5.6%; P = .012). The odds ratio of harboring occult PTM in the contralateral lobe at time of diagnosis in the setting of multifocal PTM was 23 times greater than the unifocal counterpart (95% confidence interval, 1.9-27.9). Conclusion. Multifocal PTM is a significant risk factor associated with bilateral thyroid lobe involvement at presentation. Surgeons are justified and encouraged to offer multifocal PTM patients completion thyroidectomy as part of their oncologic treatment.

Smoking Cessation and Electronic Cigarette Use among Head and Neck Cancer Patients

Objectives (1) Investigate electronic cigarette (e-cig) use among head and neck (HN) cancer patients; (2) define quit methods, success, motivations, and barriers to smoking cessation; and (3) determine the impact of e-cig use in smoking cessation. Study Design Cross-sectional study. Setting Tertiary care center. Methods An in-office survey was administered to HN cancer patients ≥19 years of age with past/present tobacco use. Patient demographics were collected. Quit methods, success, and motivations/barriers were surveyed. The Alcohol Use Disorders Identification Test was used to correlate alcohol use and cessation. Independent variables associated with cessation were studied with Fisher’s exact test and Student’s t test. Subgroup analysis was performed for e-cig users. Results Of 110 eligible patients, 106 (96%) enrolled (83% male, 82% Caucasian), of whom 69 (65%) successfully quit. Age of first tobacco use did not differ between the smoking and cessation groups (P = .14), nor did hazardous drinking (30% smoking vs 14% cessation; P = .072). “Cold turkey” (ie, stopping abruptly without smoking cessation aids) was the most common method attempted (n = 88, 83%) and most successful (n = 65, 94%). There was no statistical difference in age, sex, race, drinking, or socioeconomic status between e-cig users and nonusers. Nonusers achieved higher quit rates as compared with e-cig users (72% vs 39%; P = .0057). E-cig use did not decrease the number of cigarettes smoked (463 cigarettes/month) versus that of nonusers (341 cigarettes/month; P = .2). Seventy percent of e-cig users wore a nicotine patch. Conclusions HN cancer patients desire smoking cessation. E-cig did not decrease tobacco use, and patients who utilize e-cigs are less likely to achieve smoking cessation.

Microvascular reconstructive surgery in Operations Iraqi and Enduring Freedom: the US military experience performing free flaps in a combat zone.

BACKGROUND Local nationals with complex wounds resulting from traumatic combat injuries during Operations Iraqi Freedom and Enduring Freedom usually must undergo reconstructive surgery in the combat zone. While the use of microvascular free-tissue transfer (free flaps) for traumatic reconstruction is well documented in the literature, various complicating factors exist when these intricate surgical procedures are performed in a theater of war. METHODS The microvascular experiences of six military surgeons deployed during a 30-month period between 2006 and 2011 in Iraq and Afghanistan were retrospectively reviewed. RESULTS Twenty-nine patients presented with complex traumatic wounds. Thirty-one free flaps were performed for the 29 patients. Location of tissue defects included the lower extremity (15), face/neck (8), upper extremity (6). Limb salvage was successful in all but one patient. Six of eight patients with head and neck wounds were tolerating oral intake at the time of discharge. There were three flap losses in 3 patients; two patients who experienced flap loss underwent a successful second free or regional flap. Minor complications occurred in six patients. CONCLUSION Microvascular free tissue transfer for complex tissue defects in a combat zone is a critically important task and can improve quality of life for host-nation patients. Major US combat hospitals deployed to a war zone should include personnel who are trained and capable of performing these complex reconstructive procedures and who understand the many nuances of optimizing outcomes in this challenging environment. LEVEL OF EVIDENCE Therapeutic study, level V.

Optimal Management of Proliferative Verrucous Leukoplakia A Systematic Review of the Literature

Objective Proliferative verrucous leukoplakia (PVL) is a rare and recalcitrant form of leukoplakia. The purpose of this review is to further characterize the risk factors, clinical course, and optimal treatment for this highly aggressive, premalignant lesion. Data Sources Twenty-six articles on PVL with a total of 329 PVL cases. Review Methods A systematic review of the literature using Ovid, PubMed, Cochrane Database, and gray literature was conducted of all PVL cases reported between 1985 and 2014. Inclusion criteria required reporting of patient follow-up and recurrence rates. Data were analyzed using descriptive statistics. Student t test and Fisher exact test were used to identify factors associated with malignant transformation. Results The mean patient age was 63.9 years. Most patients were female (66.9%) and nontobacco users (65.22%). Mean follow-up was 7.4 years, with an average of 9.0 biopsies per patient during this period. Proliferative verrucous leukoplakia exhibited histopathologic features along a progressive spectrum, evolving from leukoplakia to verrucous hyperplasia and ultimately invasive carcinoma. Surgery was the most common treatment implemented, but recurrence rates among 222 patients reached 71.2%. Subgroup analysis of 277 patients identified a 63.9% malignant transformation rate, and 39.6% of patients died of their disease. Age, sex, and tobacco use were not identified as risk factors associated with progression to cancer. Conclusions Proliferative verrucous leukoplakia is a rare form of leukoplakia with a high rate of malignant transformation. It necessitates high clinical suspicion, to include a lifetime of close follow-up and repeat biopsies by a health care provider well versed in oral carcinoma.

Is sentinel lymph node biopsy the standard of care for cutaneous head and neck melanoma

Sentinel lymph node biopsy (SLNB) is considered one of the most important melanoma advancements to date. Since its inception in 1992, a plethora of data and associated controversies has emerged leading to the question: Is SLNB considered the standard of care for head and neck (HN) cutaneous melanoma?

The State of the Otolaryngology Match: A Review of Applicant Trends, “Impossible” Qualifications, and Implications

Objective This State of the Art Review aims (1) to define recent qualifications of otolaryngology resident applicants by focusing on United States Medical Licensing Examination (USMLE) scores, Alpha Omega Alpha (AOA) status, and research/publications and (2) to summarize the current literature regarding the relationship between these measures and performance in residency. Data Sources Electronic Residency Application Service, National Residency Matching Program, PubMed, Ovid, and GoogleScholar. Review Methods Electronic Residency Application Service and National Residency Matching Program data were analyzed to evaluate trends in applicant numbers and qualifications. Additionally, a literature search was performed with the aforementioned databases to identify relevant articles published in the past 5 years that examined USMLE Step 1 scores, AOA status, and research/publications. Conclusions Compared with other highly competitive fields over the past 3 years, the only specialty with decreasing applicant numbers is otolaryngology, with the rest remaining relatively stable or slightly increased. Additionally, USMLE Step 1 scores, AOA status, and research/publications do not reliably correlate with performance in residency. Implications for Practice The consistent decline in applications for otolaryngology residency is concerning and reflects a need for change in the current stereotype of the “ideal” otolaryngology applicant. This includes consideration of additional selection measures focusing on noncognitive and holistic qualities. Furthermore, otolaryngology faculty should counsel medical students that applying in otolaryngology is not “impossible” but rather a feasible and worthwhile endeavor.

A ratiometric threshold for determining presence of cancer during fluorescence-guided surgery.

Fluorescence‐guided imaging to assist in identification of malignant margins has the potential to dramatically improve oncologic surgery. However, a standardized method for quantitative assessment of disease‐specific fluorescence has not been investigated. Introduced here is a ratiometric threshold derived from mean fluorescent tissue intensity that can be used to semi‐quantitatively delineate tumor from normal tissue.

Head and Neck Cutaneous Squamous Cell Carcinoma Requiring Parotidectomy Prognostic Indicators and Treatment Selection

Objective Evaluate characteristics and risk factors for patients with advanced cutaneous squamous cell carcinoma (cSCC). Study Design Retrospective case series. Setting Tertiary care center. Patients and Methods Chart review of patients with cSCC undergoing a parotidectomy (2003-2012). Results Of 218 patients identified, 49% presented with a new primary lesion (n = 107) and 51% with a recurrence (n = 111). Parotid lymph nodes were positive in 52% of patients; 81% had a concurrent neck dissection, and 28% had cervical lymph node metastases. In 18% of patients, both parotid and cervical nodes were positive, while 44% were both parotid and cervical node negative; 33% had positive parotid and negative cervical nodes, and only 5% had negative parotid and positive cervical nodes. The overall 2- and 5-year survival rates were 0.71 and 0.58. Overall 5-year survival was lower for patients presenting with recurrent (0.49) versus new primary disease (0.69; P = .04). In addition, decreased overall 5-year survival rates were associated with cervical lymph node involvement (0.47 vs. 0.62; P = .01). There was no difference in overall survival when stratified by parotid lymph node involvement (P = .85), margin status (P = .67), perineural invasion (P = .42), facial nerve sacrifice (P = .92), or type of parotid operation performed (P = .51). Conclusions In this study, cervical, but not parotid, lymph node involvement was associated with poor outcomes in patients with advanced cSCC requiring a parotidectomy. In patients without evidence of cervical or parotid lymph node involvement, a neck dissection may be spared, given there is a 5% chance of occult disease.