Clinic-based perspectives on the integration of patient-reported outcomes (PROs) in a tertiary cancer center.

PURPOSE: This study examines providers' and clinic staff's perspectives on patient-reported outcomes (PROs) implementation at an academic medical center. METHODS: An anonymous and voluntary survey was administered to Henry Ford Cancer providers and clinic staff 18 months after PROs program implementation in September 2020, to obtain their feedback on perceived barriers, impact on workflows, and PROs administration frequency in routine cancer care. RESULTS: A total of 180 providers and 40 clinic staff were invited to complete the survey; 31% and 63% completed the survey, respectively. Approximately 68% of providers reported that electronically integrated PROs scores were either beneficial or somewhat beneficial to their patients, while only 28% of the clinic staff reported that PROs were beneficial or somewhat beneficial to patients. According to the clinic staff, the most common barriers to PROs completion included lack of patients' awareness of the utility of the program with respect to their care, patients' health status at check-in, and PROs being offered too frequently. CONCLUSION: There is favorable acceptance of the PROs program by providers, but clinic staff found it less favorable. Interventions to address barriers and improve program engagement are needed to ensure broad adoption of PROs in oncology practice.

Race, not socioeconomic disparities, correlates with survival in human papillomavirus-negative oropharyngeal cancer: A retrospective study.

PURPOSE: Investigate the impact of black versus white race, socioeconomic status (SES), and comorbidity burden on oropharyngeal cancer (OPC) survival. MATERIALS AND METHODS: This study retrospectively analyzed patients diagnosed between 1991 and 2012 at an urban tertiary care center with a high volume of head and neck cancer referrals. Data gathered included demographics, human papilloma virus (HPV) status, follow-up time, comorbidities, smoking history, and overall survival. SES was extrapolated from the 2000 and 2010 censuses. Analysis of variance, chi-square tests, multivariable Cox proportional hazards models, Cox proportional hazards regression, Kaplan Meier curves and the log-rank test were utilized. RESULTS: Of 208 charts reviewed, 192 patients met inclusion criteria. Black patients had significantly (p < 0.001) poorer survival at 1, 2, and 5 years than white patients (5-year survival: 32% vs 64%); this discrepancy persisted in only HPV-negative disease (20% vs 50%). In the HPV-negative subgroup, there was no racial difference in treatment modality received, Charlson Comorbidity Index, and proportion receiving inadequate, noncurative or no treatment. Univariate analysis identified significant differences in median household income, education level, and stage at presentation between black and white subgroups. Multivariate analysis identified white race and HPV-positive status as independent predictors of overall survival, but SES and stage at presentation were not. CONCLUSION: SES did not explain the greater survival in HPV-negative white versus black patients. This indicates that race is an independent predictor of survival; future studies should examine more accurate indicators of SES and genetic differences in tumors of black and white patients.

Does insurance type influence overall survival in patients with laryngeal squamous cell carcinoma?

OBJECTIVE: Patients with head and neck cancer with Medicaid or no insurance present at a more advanced stage and have lower survival. This study is one of the first to examine the relationship between specific insurance types and overall survival for laryngeal squamous cell carcinoma patients. STUDY DESIGN: Retrospective chart review. SETTING: Henry Ford Cancer Institute. SUBJECTS AND METHODS: A retrospective database review was performed using the Henry Ford Virtual Data Warehouse Tumor Registry. Six hundred and fifty patients diagnosed with laryngeal squamous cell carcinoma were identified. Insurance groups analyzed were fee for service, health maintenance organization, Henry Ford Medical Group - a managed care type insurance, Medicare and Medicaid/uninsured. Cox proportional hazards and Kaplan-Meier curves were generated to analyze overall survival and display survival differences respectively. RESULTS: The uninsured group had the lowest median survival time of 29.8 months (95% CI: 20.3-44.8) and the highest HR of 1.85 (95% CI 1.16-2.93) as compared to the HMO group at p < 0.001. Patients with fee for service insurance had longer overall survival compared to the other insurance types. Patients with fee for service insurance also had a high proportion of patients with advanced stage disease, but a younger mean age. Henry Ford Medical Group had a higher mean age and no statistically significant difference in survival when compared to fee for service. (p = 0.999) After controlling for socioeconomic status, insurance type remains a significant predictor of overall survival. CONCLUSIONS: Fee for service had the highest overall survival of the different insurance types, but it was only statistically significant when compared to the Medicaid/uninsured group.

INCIDENTAL THYROID NODULES: RACE/ETHNICITY DISPARITIES AND OUTCOMES.

OBJECTIVE: Black patients have a significantly lower incidence of well-differentiated thyroid cancer (WDTC) compared to all other race/ethnic groups, while white patients appear to be at greater risk. This study examines incidental thyroid nodules (ITNs) to assess whether racial disparities in WDTC arise from a differential discovery of ITNs-perhaps due to socioeconomic disparities-or reflect true differences in thyroid cancer rates. METHODS: A retrospective review was performed of all patients who underwent fine-needle aspiration (FNA) of thyroid nodules by our academic medical center's endocrinology division between January 2006 and December 2010. Medical records were reviewed to identify whether the biopsied thyroid nodule was discovered incidentally through nonthyroid-related imaging or identified by palpation. RESULTS: FNAs were performed on 1,369 total thyroid nodules in 1,141 study patients; 547 (48%) were classified as white, and 593 (52%) were classified as nonwhite. Among this cohort, 36.6% of patients underwent biopsy for an ITN. White patients were 1.6 times more likely to have undergone a biopsy for a nodule that was incidentally identified compared to nonwhites ( P<.0001). Indicators of socioeconomic status (SES) did not have a significant association with ITNs. Within the ITN cohort, 4.9% of nonwhite patients were found to have a thyroid malignancy compared to 12.9% of white patients ( P<.01). CONCLUSION: The higher incidence of thyroid cancer in white patients appears to be not only due to diagnostic bias, but also to a true difference in cancer prevalence. ABBREVIATIONS: FNA = fine-needle aspiration; ITN = incidental thyroid nodule; SEER = Surveillance Epidemiology and End Results; SES = socioeconomic status; WDTC = well-differentiated thyroid cancer.

Cognitive Function and Postoperative Outcomes in Patients with Head and Neck Cancer.

OBJECTIVE: Determine the relationship between cognitive function and postoperative outcomes. METHODS: This IRB-approved retrospective cohort study included all patients treated between August 2015 and March 2020 undergoing major surgery for aerodigestive cancer or cutaneous/thyroid cancer that required free-flap reconstruction at Henry Ford Hospital. Routine administration of the Montreal Cognitive Assessment (MoCA) was completed as part of preoperative psychosocial evaluation. Outcomes included postoperative diagnosis of delirium, discharge disposition, return to the emergency department within 30 days of surgery, and readmission within 30 days of surgery. Univariate and multivariate logistic regression were used to determine the associations between preoperative MoCA score and each outcome measure. RESULTS: One hundred thirty-five patients with HNC were included in the study (mean [SD] age, 60.7 [±10.8] years; 70.4% [n = 95] male; 83.0% [n = 112] White, 16.3% [n = 22] Black). The average preoperative MoCA score was 23.4 (SD ± 4.5). Based on the MoCA score, 35% (n = 47) scored ≥26 (i.e., normal cognitive status), 55.6% (n = 75) scored between 18 and 25 (i.e., mild impairment), 8.1% (n = 11) scored between 10 and 17 (i.e., moderate impairment), and 1.5% (n = 2) scored <10 (i.e., severe impairment). After adjusting for other variables, a lower MoCA score was associated with discharge disposition to a location other than home and prolonged length of hospital stay. CONCLUSIONS: Preoperative cognitive function in patients undergoing major head and neck surgery for head and neck cancer was associated with discharge destination and length of stay. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2999-3005, 2023.

Real time patient-reported outcome measures in patients with cancer: Early experience within an integrated health system.

BACKGROUND: While patient-reported outcome measures (PROMs) have benefit in cancer clinical trials, real-world applications are lacking. This study describes the method of implementation of a cancer enterprise-wide PROMs platform. METHODS: After establishing a multispecialty stakeholder group within a large integrated health system, domain-specific instruments were selected from the National Institutes of Health's Patient-Reported Outcomes Measurement Information System (PROMIS) instruments (pain interference, fatigue, physical function, and depression) and were administered at varying frequencies throughout each patient's cancer journey. All cancer patients with an oncologic visit were eligible to complete the PROMs prior to the visit using a patient portal, or at the time of the visit using a tablet. PROMs were integrated into clinical workflow. Clinical partnerships were essential for successful implementation. Descriptive preliminary data were compared using multivariable logistic regression to determine the factors associated with method of PROMs completion. RESULTS: From September 16, 2020 to July 23, 2021, 23 of 38 clinical units (60.5%) implemented PROMs over 2392 encounters and 1666 patients. Approximately one third of patients (n = 629, 37.8%) used the patient portal. Black patients (aOR 0.70; 95% CI: 0.51-0.97) and patients residing in zip codes with higher percentage of unemployment (aOR: 0.07, 95% CI: 0.01-0.41) were among the least likely to complete PROMs using the patient portal. CONCLUSIONS: Successful system-wide implementation of PROMs among cancer patients requires engagement from multispecialty stakeholders and investment from clinical partners. Attention to the method of PROMs collection is required in order to reduce the potential for disparities, such as Black populations and those residing in areas with high levels of unemployment.

Transcervical approach to benign parapharyngeal space tumors.

OBJECTIVES: We describe our experience with the postoperative sequelae, complications, and recurrences associated with resection of a series of parapharyngeal space (PPS) tumors via a transcervical approach without submandibular gland excision, parotidectomy, or mandibulotomy. METHODS: We performed a retrospective review of 51 cases, 40 of which were pleomorphic adenomas and 11 of which were lipomas or schwannomas. RESULTS: Of 30 fine-needle aspirations performed, 24 indicated pleomorphic adenoma before operation. Twenty-eight of the 30 fine-needle aspirations yielded diagnoses that were consistent with the final pathologic diagnoses. The average hospital stay was 1.05 days. After operation, there were 9 cases of trismus, 4 cases of "first bite" pain, and 7 cases of transient marginal nerve weakness. There were no recurrences over an average follow-up of 115 months. CONCLUSIONS: The majority of PPS tumors are benign. It is important to use an approach that allows complete tumor excision but does not impart undue postoperative morbidity. We demonstrate that the transcervical approach without submandibular gland excision, parotidectomy, or mandibulotomy is ideal for benign PPS tumors.

Association of Inventory to Measure and Assess imaGe Disturbance - Head and Neck Scores With Clinically Meaningful Body Image-Related Distress Among Head and Neck Cancer Survivors.

Objective: The Inventory to Measure and Assess imaGe disturbance - Head and Neck (IMAGE-HN) is a validated patient-reported outcome measure of head and neck cancer-related body image-related distress (BID). However, the IMAGE-HN score corresponding to clinically relevant BID is unknown. The study objective is to determine the IMAGE-HN cutoff score that identifies head and neck cancer patients with clinically relevant BID. Methods: We conducted a cross-sectional study at six academic medical centers. Individuals ≥18 years old with a history of head and neck cancer treated with definitive intent were included. The primary outcome measure was the IMAGE-HN. A Receiver Operating Characteristic curve analysis was performed to identify the IMAGE-HN score that maximized sensitivity and specificity relative to a Body Image Scale score of ≥10 (which indicates clinically relevant BID in a general oncology population). To confirm the validity of the IMAGE-HN cutoff score, we compared the severity of depressive [Patient Health Questionnaire-9 (PHQ-9)] and anxiety symptoms [Generalized Anxiety Disorder-7 (GAD-7)], and quality of life [University of Washington-QOL (UW-QOL)] in patients with IMAGE-HN scores above and below the cutoff. Results: Of the 250 patients, 70.4% were male and the mean age was 62.3 years. An IMAGE-HN score of ≥22 was the optimal cutoff score relative to a Body Image Scale score of ≥10 and represents a clinically relevant level of head and neck cancer-related BID. Relative to those with an IMAGE-HN score of <22, patients with IMAGE-HN scores of ≥22 had a clinically meaningful increase in symptoms of depression (mean PHQ-9 score difference = 5.8) and anxiety (mean GAD-7 score difference = 4.1) as well as worse physical (mean UW-QOL score difference = 18.9) and social-emotional QOL (mean UW-QOL score difference = 21.5). Using an IMAGE-HN cutoff score ≥22, 28% of patients had clinically relevant BID. Conclusion: An IMAGE-HN score of ≥22 identifies patients with clinically relevant head and neck cancer-related BID. This score may be used to detect patients who could benefit from strategies to manage their distress, select patients for studies evaluating interventions to manage head and neck cancer-related BID, and improve our understanding of the underlying epidemiology of the disorder.

Systematic review of postoperative therapy for resected squamous cell carcinoma of the head and neck: Executive summary of the American Radium Society appropriate use criteria.

BACKGROUND: The aims of this systematic review are to (a) evaluate the current literature on the impact of postoperative therapy for resected squamous cell carcinoma of the head and neck (SCCHN) on oncologic and non-oncologic outcomes and (b) identify the optimal evidence-based postoperative therapy recommendations for commonly encountered clinical scenarios. METHODS: An analysis of the medical literature from peer-reviewed journals was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. Prospective studies and methodology-based systematic reviews and meta-analyses of postoperative therapy for SCCHN were identified by searching Medline (OVID) and EMBASE (Elsevier) using controlled vocabulary terms (ie, National Library of Medicine Medical Subject Headings [MeSH], EMTREE). Study screening and selection was performed with Covidence software and full-text review. The RAND/UCLA appropriateness method was used by the expert panel to rate the appropriate use of postoperative therapy, and the modified Delphi method was used to come to consensus. RESULTS: A total of 5660 studies were identified and screened using the title and abstract, leading to 201 studies assessed for relevance using full-text review. After limitation to the eligibility criteria, 101 studies from 1977 to 2020 were identified, including 77 with oncologic endpoints and 24 with function and quality of life endpoints. All studies reported staging prior to the implementation of American Joint Committee on Cancer (AJCC-8). CONCLUSIONS: Prospective clinical studies and systematic reviews identified through the PRISMA systematic review provided good evidence for consensus statements regarding the appropriate use of postoperative therapy for resected SCCHN. Further research is needed in domains where consensus by the expert panel could not be achieved for the appropriateness of specific postoperative therapeutic interventions.

Chronic cigarette smoke extract treatment selects for apoptotic dysfunction and mitochondrial mutations in minimally transformed oral keratinocytes.

Cigarette smoke demonstrates a carcinogenic effect through chronic exposure, not acute exposures. However, current cell line models study only the acute effects of cigarette smoke. Using a cell line model, we compared the effects of acute versus chronic cigarette smoke extract (CSE) on mitochondria in minimally transformed oral keratinocytes (OKF6). OKF6 cells were treated with varying concentrations of CSE for 6 months. Cells were analyzed monthly by flow cytometry for mitochondrial membrane potential (MMP), cytochrome c release, caspase 3 activation and viability after CSE exposure. At each time point, the same assays were performed after 24 hr of valinomycin (MMP-depolarizing agent) treatment. The mitochondrial DNA of chronically CSE-treated cells was sequenced. After 6 months of CSE treatment, the cells were increasingly resistant to CSE-mediated and valinomycin-induced cell death. In addition, chronic CSE treatment caused chronic depolarization of MMP, cytochrome c release and caspase activation. Cells grown in the presence of only CSE vapor also exhibited the same resistance and chronic baseline apoptotic activation. Mitochondrial DNA sequencing found that chronic CSE-treated cells had more amino acid-changing mitochondrial mutations than acutely treated cells. CSE treatment of normal cells select for apoptotic dysfunction as well as mitochondrial mutations. These findings suggest that chronic tobacco exposure induces carcinogenesis via selection of apoptosis resistance and mitochondrial mutation in addition to previously known genotoxic effects that were found by acute treatments. Chronic models of tobacco exposure on upper aerodigestive epithelia may be more insightful than models of acute exposure in studying head and neck carcinogenesis.

Mitochondrial mutations contribute to HIF1alpha accumulation via increased reactive oxygen species and up-regulated pyruvate dehydrogenease kinase 2 in head and neck squamous cell carcinoma.

PURPOSE: Mitochondrial mutations have been identified in head and neck squamous cell carcinoma (HNSCC), but the pathways by which phenotypic effects of these mutations are exerted remain unclear. Previously, we found that mitochondrial ND2 mutations in primary HNSCC increased reactive oxygen species (ROS) and conferred an aerobic, glycolytic phenotype with HIF1alpha accumulation and increased cell growth. The purpose of the present study was to examine the pathways relating these alterations. EXPERIMENTAL DESIGN: Mitochondrial mutant and wild-type ND2 constructs were transfected into oral keratinocyte immortal cell line OKF6 and head and neck cancer cell line JHU-O19 and established transfectants. The protein levels of HIF1alpha, pyruvate dehydrogenease (PDH), phosphorylated PDH, and pyruvate dehydrogenease kinase 2 (PDK2), together with ROS generation, were compared between the mutant and the wild type. Meanwhile, the effects of small molecule inhibitors targeting PDK2 and mitochondria-targeted catalase were evaluated on the ND2 mutant transfectants. RESULTS: We determined that ND2 mutant down-regulated PDH expression via up-regulated PDK2, with an increase in phosphorylated PDH. Inhibition of PDK2 with dichloroacetate decreased HIF1alpha accumulation and reduced cell growth. Extracellular treatment with hydrogen peroxide, a ROS mimic, increased PDK2 expression and HIF1alpha expression, and introduction of mitochondria-targeted catalase decreased mitochondrial mutation-mediated PDK2 and HIF1alpha expression and suppressed cell growth. CONCLUSIONS: Our findings suggest that mitochondrial ND2 mutation contributes to HIF1alpha accumulation via increased ROS production, up-regulation of PDK2, attenuating PDH activity, thereby increasing pyruvate, resulting in HIF1alpha stabilization. This may provide insight into a potential mechanism, by which mitochondrial mutations contribute to HNSCC development.

EIF2C is overexpressed and amplified in head and neck squamous cell carcinoma.

AIM: To discover putative oncogenes in head and neck squamous cell carcinoma (HNSCC) by integrating data from whole-genome comparison of array-based comparative genomic hybridization (CGH) and expression microarray analysis of HNSCC. METHODS: We integrated published data defining regions of loss/gain identified from the profiling of 21 HNSCC using high-resolution (<1 Mb) CGH arrays and data from an mRNA expression microarray (approx. 12,000 genes) comparing 6 normal tissues and 8 HNSCC tumor tissues. Eukaryotic translation initiation factor 2C subunit 2 (EIF2C2) was found to be the most significantly overexpressed gene by mRNA expression array, and corresponded to the most common region of amplification found by the CGH array described by Sparano et al. We validated EIF2C2 overexpression in primary tissue, overexpression and amplification in HNSCC lines (JHU-011, JHU-012, FADU) relative to a minimally transformed oral keratinocyte cell line (OKF6) and performed knockdown experiments. RESULTS: The tumor tissues had an average mRNA expression level of 123 (SD = 49) compared to the normal tissues (18.6, SD = 10) (p = 0.0005) by expression array. Quantitative RT-PCR validation of our expression arrays found that normal tissues had an average expression of 0.76 (SE = 0.08) and tumor tissues of 2.1 (SE = 0.35) (p = 0.0008). EIF2C2 was found to be amplified and overexpressed in 3 HNSCC cell lines. Knockdown of EIF2C2 in cell lines (JHU-012 and JHU-011) inhibited proliferation. CONCLUSION: EIF2C2 is amplified and overexpressed in HNSCC cell lines and primary tumors and functionally significant in cell lines.

Inactivation of the tumor suppressor genes causing the hereditary syndromes predisposing to head and neck cancer via promoter hypermethylation in sporadic head and neck cancers.

Fanconi anemia (FA) and dyskeratosis congenita (DC) are rare inherited syndromes that cause head and neck squamous cell cancer (HNSCC). Prior studies of inherited forms of cancer have been extremely important in elucidating tumor suppressor genes inactivated in sporadic tumors. Here, we studied whether sporadic tumors have epigenetic silencing of the genes causing the inherited forms of HNSCC. Using bisulfite sequencing, we investigated the incidence of promoter hypermethylation of the 17 Fanconi- and DC-associated genes in sporadic HNSCC. Genes that only showed methylation in the tumor patients were chosen for quantitative methylation-specific PCR (qMSP) in a set of 45 tumor and 16 normal patients. Three gene promoters showed differences in methylation: FancB (FAAP95, FA core complex), FancJ (BRIP1, DNA Helicase/ATPase), and DKC1 (dyskeratin). Bisulfite sequencing revealed that only FancB and DKC1 showed no methylation in normal patients, yet the presence of promoter hypermethylation in tumor patients. On qMSP, 1/16 (6.25%) of the normal mucosal samples from non-cancer patients and 14/45 (31.1%) of the tumor patients demonstrated hypermethylation of the FancB locus (p < 0.05). These results suggest that inactivation of FancB may play a role in the pathogenesis of sporadic HNSCC.

Surgical impact of a dedicated endocrine surgeon on an academic otolaryngology department.

OBJECTIVES: Endocrine surgery is emerging as a dedicated subspecialty in otolaryngology. We assess the impact of an endocrine surgeon on an academic otolaryngology department's thyroid and parathyroid surgery volume. METHODS: A retrospective study of overall endocrine caseloads and resident case logs at a single academic center in the Midwest was performed. All thyroid and parathyroid cases performed by the otolaryngology department at an academic center from 2011 to 2017 were reviewed. In September 2012, an otolaryngologist who had completed an American Head and Neck Society endocrine surgery fellowship joined the faculty. The volume of endocrine surgery performed by the residents was also analyzed. Comparison of means and linear regression models were performed. RESULTS: From 2011 to 2012, the department performed a mean of 77 thyroid and 11.5 parathyroid surgeries annually. After the endocrine surgeon joined the department, this increased to an average of 212.8 thyroidectomies (P < 0.01) and 72.4 parathyroidectomies (P < 0.01) a year. The head and neck surgeons and generalists still performed an average of 42.4 thyroidectomies and 2.6 parathyroidectomies a year. For graduating residents, the average number of thyroid/parathyroid cases increased from 42.5 in 2012 to 151 in 2016. CONCLUSION: The addition of a fellowship-trained endocrine surgeon substantially increased the thyroid and parathyroid surgical volume of the otolaryngology department. Importantly, generalists and head and neck surgeons in the department continued to perform a significant number of these cases. Departments seeking similar surgical growth and expanded resident experience may consider the value of engaging a dedicated endocrine surgeon. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:832-835, 2020.

Analysis of patient factors associated with 30-day mortality after tracheostomy.

OBJECTIVE: Mortality has been reported to be 22% to 45% in patients with a tracheostomy. To better counsel patients and families, we aimed to determine the effect of body mass index (BMI), socioeconomic status (SES), and the 17 conditions of the Charlson comorbidity index (CCI) on 30-day survival posttracheostomy. METHODS: This retrospective cohort study identified adult patients enrolled from our institution in the Global Tracheostomy Collaborative database from March 2014 to June 2015. Data collected included age, BMI, residential zip code, and comorbidities. Cox proportionate univariate and multivariate analyses were used to measure the impact of BMI, SES, and CCI variables with 30-day posttracheostomy survival. We used geocoding as a surrogate for patients' SES. We used Deyo's modification of the CCI, which utilized International Classification of Diseases, 9th Revision, codes to identify comorbidities. RESULTS: Of 326 tracheostomies identified, the 30-day mortality rate was 15.6%. No significant differences were noted in BMI or in any of the SES categories between survivors and nonsurvivors. CCI was significantly higher in the 30-day mortality group. Congestive heart failure (hazard ratio [HR] = 2.39), severe liver disease (HR = 3.15), and peripheral vascular disease (HR = 2.62) were found to significantly impact 30-day survival. CONCLUSION: Higher CCI and specifically severe liver disease, congestive heart failure, and peripheral vascular disease were associated with increased 30-day mortality posttracheostomy. No association was found between BMI or SES and 30-day survival. This study identified three comorbidities that independently affect mortality in tracheostomy patients, which should be discussed with patients and families before tracheostomy. LEVEL OF EVIDENCE: 3 Laryngoscope, 129:847-851, 2019.

Flexible model for patient engagement: Achieving quality outcomes and building a research agenda for head and neck cancer.

BACKGROUND: This article describes the benefits of patient-driven research in the field of head and neck oncology, reviews lessons learned from establishing partnerships with patients and caregivers, and serves as a model for further patient-driven research endeavors. METHODS: Head and neck cancer survivors underwent training including that of effective communication and the basics of research methodology. They then drove the agendas for monthly meetings that included a multidisciplinary team of providers, facilitated by a physician champion (S.S.C.). RESULTS: The advisors reported concrete areas for improvement of the clinical flow, including the formation of a dental oncology clinic and a post-treatment survivorship clinic. They also refined research topics of interest, such as treatment regret. The advisors have also driven efforts to increase public awareness and have participated in cancer symposiums and local presentations. CONCLUSION: Patient-driven research improves the relevance and implementation of head and neck oncology research and clinical processes.

Impact of smoking on pathological features in oral cavity squamous cell carcinoma.

OBJECTIVES: We sought to determine whether smokers with oral cavity squamous cell carcinoma (OCSCC) have tumors with more adverse pathological features than in nonsmokers and whether or not these are predictive of outcomes. MATERIALS AND METHODS: We retrospectively identified 163 patients with American Joint Committee on Cancer stages I-IVa OCSCC diagnosed between 2005 and 2015 and treated with curative intent. A pathological risk score (PRS) was calculated using the National Comprehensive Cancer Network adverse risk factors: positive margin, extracapsular extension of lymph node metastases, pT3 or pT4 primary, N2 or N3 nodal disease, perineural invasion, and lymphovascular space invasion. Multivariable models were constructed to determine the independent predictors of overall survival (OS), recurrence-free survival (RFS), and PRS. RESULTS: A total of 108 (66.26%) were smokers and 55 nonsmokers. Three-year actuarial OS and RFS were 62% and 68% in smokers and 81% and 69% in nonsmokers, respectively (P = 0.06 and P = 0.63). Smokers were more likely to have advanced disease stage and tumors with aggressive pathological features than nonsmokers. Smokers had significantly worse PRS (mean ± standard deviation; 2.38 ± 2.19, median; 2.00) than nonsmokers (0.89 ± 1.21, 0.00) (P < 0.001). Older age, higher PRS, and smoking status were independent predictors of OS. Smoking or PRS did not predict for worse RFS. On multivariate analysis, independent predictors of PRS were smoking status and grade (P < 0.001). CONCLUSION: In patients with OCSCC, smokers have more aggressive disease as evidenced by more adverse pathological features than nonsmokers. Moreover, smoking is an independent predictor of OS but not RFS. The PRS is a significant predictor of OS and needs validation in the future studies.

Factors associated with employment discontinuation among older and working age survivors of oropharyngeal cancer.

BACKGROUND: Oropharyngeal cancer survivors experience difficulty returning to work after treatment. To better understand specific barriers to returning to work, we investigated factors associated with discontinuing employment among older and working-age survivors. METHODS: The sample included 675 oropharyngeal cancer survivors (median: 6 years posttreatment) diagnosed from 2000 to 2013 and employed at diagnosis. Relative risk models were constructed to examine the independent associations of demographic and health factors, and symptom experiences per the MD Anderson Symptom Inventory - Head and Neck Module (MDASI-HN) with posttreatment employment, overall and by age (<60 years vs ≥60 years at survey). RESULTS: Symptom interference was not statistically significantly associated with posttreatment employment status among respondents ≥60 years. Among working-age respondents <60 years, symptom interference was strongly associated with posttreatment employment. CONCLUSIONS: Efforts to assess and lessen symptom burden in working-age survivors should be evaluated as approaches to support regaining core functions needed for continued employment.

MicroRNA alterations in head and neck squamous cell carcinoma.

MicroRNAs (mirs) are small noncoding RNA molecules (~22 nucleotides) that regulate posttranscriptional gene expression. Currently, there has not been a comprehensive study of their role in primary head and neck squamous cell carcinoma (HNSCC). To determine the role of mirs in HNSCC, we screened for altered microRNA expression in HNSCC primary tissue and cell lines. We then further tested the functional impact of alterations of specific mirs. An initial screening of 4 primary HNSCC, 4 normal mucosal controls and 4 HNSCC cell lines was analyzed for mature microRNA expression by microarray. Significance was determined using significance analysis of microarrays (SAM). Nine microRNAs were found by SAM to be upregulated or downregulated in tumor tissue including mir-21, let-7, 18, 29c, 142-3p, 155, 146b (overexpressed) and 494 (underexpressed). Mir-21 was validated by qRT-PCR. Functional validation by growth assays was performed, further validating mir-21. Transfection of mir-21 into JHU-011 and JHU-012 cell lines showed a 39% increase in cell growth at 72 hr relative to controls (p < 0.05). Transfection of the inhibitor into JHU-O12 cell lines showed a 92% decrease in cell growth relative to controls at 72 hr (p < 0.05). In addition, flow cytometry analysis of JHU-012 cells 48 hr after mir-21 inhibitor transfection showed a statistically significant increase in cytochrome c release and increased apoptosis. These differentially expressed microRNAs may be of interest as potential novel oncogenes and tumor suppressor genes in HNSCC. Mir-21 is a putative oncogenic microRNA in head and neck cancer.

Nasopharyngeal hairy polyp with recurrence in the middle ear.

A 6-year-old girl was referred to The Johns Hopkins Hospital for a suspected congenital cholesteatoma. The lesion was determined to be a recurrence of a nasopharyngeal hairy polyp removed in the postnatal period. Simple excision is normally regarded as curative: malignant transformation and local recurrence do not occur. Our case is exceptional in that incomplete excision of the nasopharyngeal polyp was followed by re-growth and extension into the middle ear over a 6-year period. Thus, not all hairy polyps are static lesions. Indeed, this case documents progressive growth of a hairy polyp during physical development of a child, and indicates a potential for local recurrence following incomplete excision. A review of possible etiologies is conducted.