Prioritizing Diversity in Otolaryngology-Head and Neck Surgery: Starting a Conversation.

Academic centers embody the ideals of otolaryngology and are the specialty's port of entry. Building a diverse otolaryngology workforce-one that mirrors society-is critical. Otolaryngology continues to have an underrepresentation of racial and ethnic minorities. The specialty must therefore redouble efforts, becoming more purposeful in mentoring, recruiting, and retaining underrepresented minorities. Many programs have never had residents who are Black, Indigenous, or people of color. Improving narrow, leaky, or absent pipelines is a moral imperative, both to mitigate health care disparities and to help build a more just health care system. Diversity supports the tripartite mission of patient care, education, and research. This commentary explores diversity in otolaryngology with attention to the salient role of academic medical centers. Leadership matters deeply in such efforts, from culture to finances. Improving outreach, taking a holistic approach to resident selection, and improving mentorship and sponsorship complement advances in racial disparities to foster diversity.

Speech and swallowing outcomes after laryngectomy for the dysfunctional irradiated larynx.

PURPOSE: To characterize outcomes of total laryngectomy for the dysfunctional larynx after radiation. METHODS: Retrospective case series of all subjects who underwent total laryngectomy for the irradiated dysfunctional larynx between 2000 and 2018 at an NCI-designated comprehensive cancer center at a single tertiary care academic medical center. Main outcomes included enteral tube feeding dependency, functional tracheoesophageal speech, and number and timing of postoperative pharyngeal dilations. RESULTS: Median time from radiation to laryngectomy was 2.8 years (range 0.5-27 years). Functional outcomes were analyzed for the 32 patients with 1-year follow-up. Preoperatively, 81% required at least partial enteral tube feeding, as compared to 34% 1-year postoperatively (p = 0.0003). At 1 year, 81% had achieved functional tracheoesophageal speech, which was associated with cricopharyngeal myotomy (p = 0.04, HR 0.04, 95% CI 0.002-0.949). There were 34% of subjects who required at least one pharyngeal dilation for stricture by 1 year postoperatively. Over half (60%) of the cohort were dilated over the study period. CONCLUSIONS: Laryngectomy for the dysfunctional larynx improves speech and swallowing outcomes in many patients. Cricopharyngeal myotomy is associated with improved postoperative voice. While the need for enteral feeding is decreased, persistent postoperative swallowing dysfunction is common. Careful patient selection and education regarding functional expectations are paramount.

Patient-reported financial toxicity and adverse medical consequences in head and neck cancer.

OBJECTIVES: Financial toxicity (FT) is a significant barrier to high-quality cancer care, and patients with head and neck cancer (HNCA) are particularly vulnerable given their need for intensive support, daily radiotherapy (RT), and management of long-term physical, functional, and psychosocial morbidities following treatment. We aim to identify predictors of FT and adverse consequences in HNCA following RT. MATERIALS AND METHODS: We performed a prospective survey study of patients with HNCA seen in follow-up at an academic comprehensive cancer center (CCC) or Veterans Affairs hospital between 05/2016 and 06/2018. Surveys included validated patient-reported functional outcomes and the COST measure, a validated instrument for measuring FT. RESULTS: The response rate was 86% (n = 63). Younger age and lower median household income by county were associated with lower COST scores (i.e., worse FT) on multivariable analysis (p = .045 and p = .016, respectively). Patients with worse FT were more likely to skip clinic visits (RR (95% CI) 2.13 (1.23-3.67), p = .007), be noncompliant with recommended supplements or medications (1.24 (1.03-1.48), p = .02), and require supportive infusions (1.10 (1.02-1.20), p = .02). At the CCC, patients with worse FT were more likely to require feeding tubes (1.62 (1.14-2.31), p = .007). Overall, 36% reported that costs were higher than expected, 48% were worried about paying for treatment, and 33% reported at least a moderate financial burden from treatment. CONCLUSION: HNCA patients experience substantial FT from their diagnosis and/or therapy, with potential implications for medical compliance, QOL, and survivorship care.

Mutational profiles of persistent/recurrent laryngeal squamous cell carcinoma.

BACKGROUND: We sought to describe targeted DNA sequencing data of persistent/recurrent laryngeal squamous cell carcinoma (LSCC) and to compare gene-specific alteration frequencies with that of primary, untreated LSCC specimens from The Cancer Genome Atlas (TCGA). METHODS: The tumors of 21 patients with persistent/recurrent LSCC were subjected to targeted DNA sequencing using the Ion AmpliSeq Comprehensive Cancer Panel. Gene-specific alteration frequencies were compared (Chi-Square test) to primary, untreated LSCC sequencing data from TCGA using the cBioPortal platform. RESULTS: Persistent/recurrent LSCC was characterized by a high rate of inactivating alterations in TP53 (38.1%) and CDKN2A (33%), amplification events of CCND1 (19.1%), and ERBB2 (14.3%), and NOTCH1 (19.1%) mutations. Comparison of primary vs persistent/recurrent LSCC revealed significant differences in alteration frequencies of eight critical genes: BAP1, CDKN2A, DCUN1D1, MSH2, MTOR, PIK3CA, TET2, and TP53. CONCLUSIONS: Our results provide preliminary support for a distinct mutational profile of persistent/recurrent LSCC that requires validation in larger cohorts.

Sentinel Lymph Node Biopsy for Cutaneous Squamous Cell Carcinoma on the Head and Neck.

Importance: Metastasis of cutaneous squamous cell carcinoma (SCC) to the nodal basin is associated with a poor prognosis. The role of sentinel lymph node biopsy (SLNB) for regional staging in patients diagnosed with SCC is unclear. Objective: To evaluate a single institution's experience with use of SLNB for regional staging of SCC on the head and neck. Design, Setting, and Participants: A retrospective review of 53 patients who were diagnosed with SCC on the head and neck, at high risk for nodal metastasis based on National Comprehensive Cancer Network (NCCN) risk factors, and treated with wide local excision (WLE) and SLNB from December 1, 2010, through January 30, 2015, in a single academic referral center was performed. The follow-up period ended November 5, 2015. Sentinel lymph node biopsy paraffin blocks were retrieved and processed retrospectively with serial sectioning and immunohistochemical analysis (IHC) in cases with nodal recurrence following a negative SLNB. Main Outcomes and Measures: Sentinel node (SN) identification rate, SLNB positivity rate, local recurrence, regional nodal recurrence, and distant recurrence. Results: In 53 patients with 54 tumors the SN identification rate was 94%. The SLNB positivity rate was 11.3%. On more thorough tissue processing and IHC, metastatic SCC was identified in 2 of 5 (40%) cases previously deemed negative. After reclassification of these cases, the adjusted SLNB positivity rate was 15.1%. The adjusted rate of false omission was 7.1% (95% CI, 2%-19%). Nodal disease developed in 20.8% overall. Angiolymphatic invasion (Cohen d, 3.52; 95% CI, 1.83-5.21), perineural invasion (Cohen d, 0.81; 95% CI, 0.09-1.52), and clinical size (Cohen d, 0.83; 95% CI, 0.05-1.63) were associated with the presence of nodal disease. Conclusions and Relevance: Rigorous study of SLNB for cutaneous SCC incorporating prospectively-collected comprehensive data sets based on standardized treatment algorithms is justified with potential to modify clinical practice. Our study demonstrates the critical importance of serial sectioning and IHC of the SLNB specimen for accurate diagnosis. Use of the NCCN guidelines may facilitate identification of patients with SCC at high risk for nodal metastasis.

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

OBJECTIVES/HYPOTHESIS: 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? STUDY DESIGN: English literature (1990-2014) review. METHODS: The PubMed database search was conducted using key terms "melanoma" and "sentinel node." This review included both dedicated HN SLNB studies and larger prospective SLNB studies, in which HN patients were included among the cohort. Bibliography cross-referencing was conducted to ensure a comprehensive search. RESULTS: SLNB is safe and accurate in the HN region. Review of large prospective SLNB trials identified the pathologic status of the SLN as the most important prognostic factor for recurrence and survival. Early lymphadenectomy following a positive SLNB imparts a survival benefit. CONCLUSIONS: Our review of the current literature suggests that SLNB is the standard of care for selected cases of HN cutaneous melanoma. It is now incorporated into the American Joint Committee on Cancer staging system, the National Comprehensive Cancer Network practice guidelines, and numerous national and international consensus statements.

Chemoselection as a strategy for organ preservation in patients with T4 laryngeal squamous cell carcinoma with cartilage invasion.

OBJECTIVES/HYPOTHESIS: High rates of overall survival (OS) and laryngeal preservation were achieved in two sequential phase II clinical trials in patients with stage III/IV laryngeal squamous cell carcinoma (SCC). Patients were treated with chemoradiation after a >50% primary tumor response to one cycle of neoadjuvant chemotherapy (IC). We analyzed outcomes for T4 patients with cartilage invasion from both studies. STUDY DESIGN: Retrospective. METHODS: Records from 36 patients with T4 SCC of the larynx with cartilage invasion alone (n = 16) or cartilage invasion and extralaryngeal spread (n = 20) were retrospectively reviewed. All were treated with one cycle of cisplatin (100 mg/m(2)) [or carboplatin (AUC 6)] and 5-fluorouracil (1,000 mg/m(2)/d for 5 days) (P+5FU). Those achieving >50% response at the primary tumor received chemoradiation (70 Gy; 35 fractions with concurrent cisplatin-100 mg/m(2) [carboplatin (AUC 6)] every 21 days for 3 cycles), followed by adjuvant P+5FU for complete histologic responders (CHR). Patients with <50% response after IC underwent total laryngectomy and postoperative radiation. RESULTS: Twenty-nine of 36 patients (81%) had >50% response following IC. Of these, 27 received definitive chemoradiation, 23 (85%) obtained CHR, with 58% laryngeal preservation rate. The 3-year OS was 78%, and the disease-specific survival was 80% (median follow-up 69 months). Following chemoradiation, 8/11 (73%) patients with an intact larynx had >75% understandable speech, 6/36 (17%) were g-tube dependent and 6/36 (17%) were tracheostomy dependent. CONCLUSIONS: Our results suggest that chemo-selection is a feasible organ preservation alternative to total laryngectomy for patients with T4 laryngeal SCC with cartilage invasion.

Chemoselection as a strategy for organ preservation in advanced oropharynx cancer: response and survival positively associated with HPV16 copy number.

PURPOSE: To test induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CRT) or surgery/radiotherapy (RT) for advanced oropharyngeal cancer and to assess the effect of human papilloma virus (HPV) on response and outcome. PATIENTS AND METHODS: Sixty-six patients (51 male; 15 female) with stage III to IV squamous cell carcinoma of the oropharynx (SCCOP) were treated with one cycle of cisplatin (100 mg/m(2)) or carboplatin (AUC 6) and with fluorouracil (1,000 mg/m(2)/d for 5 days) to select candidates for CRT. Those achieving a greater than 50% response at the primary tumor received CRT (70 Gy; 35 fractions with concurrent cisplatin 100 mg/m(2) or carboplatin (AUC 6) every 21 days for three cycles). Adjuvant paclitaxel was given to patients who were complete histologic responders. Patients with a response of 50% or less underwent definitive surgery and postoperative radiation. Pretreatment biopsies from 42 patients were tested for high-risk HPV. RESULTS: Fifty-four of 66 patients (81%) had a greater than 50% response after IC. Of these, 53 (98%) received CRT, and 49 (92%) obtained complete histologic response with a 73.4% (47 of 64) rate of organ preservation. The 4-year overall survival (OS) was 70.4%, and the disease-specific survival (DSS) was 75.8% (median follow-up, 64.1 months). HPV16, found in 27 of 42 (64.3%) biopsies, was associated with younger age (median, 55 v 63 years; P = .016), sex (22 of 30 males [73.3%] and five of 12 females [41.7%]; P = .08), and nonsmoking status (P = .037). HPV titer was significantly associated with IC response (P = .001), CRT response (P = .005), OS (P = .007), and DSS (P = .008). CONCLUSION: Although the numbers in this study are small, IC followed by CRT is an effective treatment for SCCOP, especially in patients with HPV-positive tumors; however, for patients who do not respond to treatment, alternative treatments must be developed.

Voice and swallowing outcomes of an organ-preservation trial for advanced laryngeal cancer.

INTRODUCTION: Organ-preservation treatment approaches for advanced laryngeal cancer patients that use combination chemoradiotherapy result in cure rates similar to primary laryngectomy with postoperative radiotherapy. In the national VA Larynx Cancer Trial, successful organ preservation was associated with an overall improvement in quality of life but not in subjective speech compared with long-term laryngectomy survivors. As part of a Phase II clinical trial, a prospective study of speech and swallowing results was conducted to determine if larynx preservation is associated with improved voice and swallowing compared with results in patients who require salvage laryngectomy. SUBJECTS: A total of 97 patients with advanced laryngeal cancer (46 Stage III, 51 Stage IV) were given a single course of induction chemotherapy (cisplatin 100 mg/m2 on Day 1 and 5-FU 1,000 mg/m2/day x 5 days), followed by assessment of response. Patients with less than 50% response underwent early salvage laryngectomy, and patients with 50% or better response underwent concurrent chemoradiation (72 Gy and cisplatin 100 mg/m2 on Days 1, 22, and 43), followed by two cycles of adjuvant chemotherapy (DDP/5-FU). Direct laryngoscopy and biopsy were performed 8 weeks after radiation therapy to determine final tumor response. Late salvage surgery was performed on patients with persistent or recurrent disease. METHODS: Completed survey data on voice and swallowing utilizing the Voice-Related Quality of Life Measure (V-RQOL) and the List Performance Status Scale for Head and Neck Cancer Patients (PSS-HN) were obtained from 56 patients who were alive and free of disease at the time of survey, with a minimum follow-up of 8 months. Comparisons were made between patients with an intact larynx (n = 37) vs. laryngectomy (n = 19), as well as early (n = 12) vs. late salvage laryngectomy (n = 7). Multivariate analysis was performed to determine factors predictive of voice and swallowing outcomes. Overall 3-year determinant survival was 87%, with median follow-up of 40 months. RESULTS: Patients with an intact larynx demonstrated significantly higher (p = 0.02) mean V-RQOL scores (80.3) than did laryngectomy patients (65.4). This finding was consistent in the social-emotional (p = 0.007) and physical functioning domains (p = 0.03). No differences in V-RQOL scores were found in comparisons between early and late salvage laryngectomy. Multiple linear regression revealed that predictors of higher total V-RQOL scores include lower T stage (p = 0.03), organ preservation (p = 0.0007), and longer duration since treatment (p = 0.01). Understandability of speech was better in patients with an intact larynx (p = 0.001). Overall swallowing function was comparable between groups. Multiple logistic regression revealed that longer duration since treatment (p = 0.03, odds ratio = 1.1) and lower maximal mucositis grade (p = 0.03, odds ratio = 0.3) were predictive of higher likelihood of eating in public. Nutritional mode consisting of oral intake alone without nutritional supplements was achieved in 88.9% of patients with an intact larynx compared with 64.3% of laryngectomees (p = 0.09). CONCLUSIONS: Voice-related quality of life is better in patients after chemoradiation therapy compared with salvage laryngectomy. Earlier salvage, although known to be associated with fewer surgical complications, did not result in improved voice; however, the number of patients analyzed is small. Overall swallowing function is good in all patients; however, patients with an intact larynx are more likely to obtain nutrition with oral intake alone without supplements. Such measures of function and quality of life are important endpoints to help judge overall effectiveness as newer, more aggressive treatment protocols with added toxicities are developed and evaluated.

Leech therapy for patients with surgically unsalvageable venous obstruction after revascularized free tissue transfer.

OBJECTIVE: To assess the efficacy and associated complications of a leech therapy protocol used for patients with a head and neck free tissue transfer in whom flap viability is threatened because of surgically unsalvageable venous obstruction. DESIGN: Medical record review of a prospective protocol. SETTING: Tertiary care academic medical center. PATIENTS: Of the 450 free tissue transfers to the head and neck region performed by our microvascular program from January 1, 1995, to October 31, 2000, 8 patients (1.8%) developed venous obstruction not considered salvageable by conventional surgical or thrombolytic therapy. INTERVENTIONS: All 8 patients were placed on a protocol using leeches (Hirudo medicinalis), intensive care unit monitoring, antithrombotic pharmacotherapy, frequent hematologic evaluation, blood transfusions as needed, and antibiotic prophylaxis for Aeromonas hydrophila. MAIN OUTCOME MEASURES: Flap salvage rate, number of leeches used per patient, time needed for inosculation, duration of intensive care unit admission, transfusion requirement per patient, and complications during leech therapy. RESULTS: All 8 flaps survived with the application of this protocol. An average of 215 leeches were used per patient, and the average time needed for inosculation was 6.6 days. The average duration in the intensive care unit was 9.6 days. The morbidity of our protocol was substantial, with intensive care unit psychosis, prerenal azotemia, and large transfusion requirements being the most frequent complications. An average of 13 U of packed red blood cells per patient was necessary. CONCLUSIONS: Aggressive application of the presented leech therapy protocol can salvage free tissue transfers with venous obstruction that are otherwise unsalvageable. The associated morbidity can be marked. Thus, judicious application of this protocol for flap preservation is essential.

Tumor angiogenesis as a predictive marker for organ preservation in patients with advanced laryngeal carcinoma.

BACKGROUND: The purpose of this study was to retrospectively investigate tumor angiogenesis as a predictive marker for response to neoadjuvant chemotherapy, organ preservation, and survival in patients with advanced laryngeal carcinoma. METHODS: A total of 332 patients with stage III (188 patients) or stage IV (144 patients) squamous cell carcinoma of the larynx were entered in the prospective trial conducted by the Department of Veteran Affairs Laryngeal Cancer Study Group. Of this patient population, 20 pretreatment biopsy specimens were available from the chemotherapy arm for immunohistochemical analysis of Factor VIII expression. Two blinded investigators determined microvessel density in each patient by manual inspection of 10 high-power (400 x) fields (HPF). RESULTS: The patients who had a partial response (>50% decrease in tumor volume) or complete response to chemotherapy had a mean value of 20.90 (+/- 8.09 standard deviation [SD]) blood vessels per HPF. Those who did not respond to chemotherapy and thus required a total laryngectomy had a mean value of 32.99 (+/- 10.10 SD) vessels per HPF. The difference of the means was statistically significant using a two-tailed t test (P < .0085). Kaplan-Meier survival curve analysis also revealed that patients with vessel counts above the mean tended to have poorer survival than those below the mean regardless of treatment selection. The most-vascular tumors, those greater than 1 SD above the mean, had a statistically significant difference in survival and laryngeal preservation (P = .0345). CONCLUSIONS: These results indicate that tumor angiogenesis, as measured by number of vessels per HPF, was associated with decreased responsiveness to chemotherapy and radiation for larynx preservation. The most-vascular tumors also were associated with poorer survival than those with lesser degrees of angiogenesis.