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We sought to determine whether detection of cartilage invasion (CI) by computed tomography predicts oncologic outcomes after primary total laryngectomy.Retrospective cohort study comparing oncologic outcomes between radiologic versus pathologic diagnosis.Assessment of clear CI versus gestalt CI resulted in 84% versus 48% specificity, 90.9% versus 80.3% positive predictive value (PPV), 60.6% versus 80.3% sensitivity, 44.7% versus 48% negative predictive value (NPV), respectively. Disease-free survival (DFS) was similar between cT4a and cT3/cT2 patients (p = 0.87). DFS trended towards superiority among pT3/pT2 versus pT4a patients (p = 0.18). DFS was similar among patients with CI on radiologist gestalt versus no CI (p = 0.94). Histologically confirmed CI was associated with a hazard ratio (HR) of 1.46 (p = 0.27), gestalt CI 1.13 (p = 0.70), and clear CI 1.61 (p = 0.10) for DFS.Gestalt determination of CI results in high sensitivity but low specificity, while clear determination of CI results in moderate sensitivity and high specificity.

Hypofractionated radiation therapy is not commonly used in head and neck cancers (HNC) due to increased toxicity observed in historical cohorts. This study reviews our institutional experience using hypofractionated intensity modulated radiation therapy (H-IMRT) for HNC.A retrospective cohort study of 56 patients with HNC treated with H-IMRT with ≥50 Gy in 20 fractions was conducted. The primary outcomes were acute and late toxicity.Two-year locoregional control was 87% and median overall survival was 46 months. There were no acute or late grade 4 or 5 toxicities. Acute grade 2 and 3 toxicity was seen in 79% (N=44) and 25% (N=14), respectively. Late grade 2 toxicity was seen in 9% (N=5). No patients required the placement of a feeding tube or tracheostomy.H-IMRT for the definitive or post-operative treatment of HNC using ≥50 Gy in 20 fractions appears safe and well tolerated with modest toxicity.

Demographic and expression data

Supplementary Figure 1 from Gene Expression Differences Associated with Human Papillomavirus Status in Head and Neck Squamous Cell Carcinoma

Human papillomavirus (HPV) is associated with a subset of head and neck squamous cell carcinoma (HNSCC). Between 15% and 35% of HNSCCs harbor HPV DNA. Demographic and exposure differences between HPV-positive (HPV+) and negative (HPV−) HNSCCs suggest that HPV+ tumors may constitute a subclass with different biology, whereas clinical differences have also been observed. Gene expression profiles of HPV+ and HPV− tumors were compared with further exploration of the biological effect of HPV in HNSCC. Thirty-six HNSCC tumors were analyzed using Affymetrix Human 133U Plus 2.0 GeneChip and for HPV by PCR and real-time PCR. Eight of 36 (22%) tumors were positive for HPV subtype 16. Statistical analysis using Significance Analysis of Microarrays based on HPV status as a supervising variable resulted in a list of 91 genes that were differentially expressed with statistical significance. Results for a subset of these genes were verified by real-time PCR. Genes highly expressed in HPV+ samples included cell cycle regulators (p16INK4A, p18, and CDC7) and transcription factors (TAF7L, RFC4, RPA2, and TFDP2). The microarray data were also investigated by mapping genes by chromosomal location (DIGMAP). A large number of genes on chromosome 3q24-qter had high levels of expression in HPV+ tumors. Further investigation of differentially expressed genes may reveal the unique pathways in HPV+ tumors that may explain the different natural history and biological properties of these tumors. These properties may be exploited as a target of novel therapeutic agents in HNSCC treatment.

Background Over 450,000 individuals are hospitalized with burns annually and roughly 35% are scald burns. Children younger than 5 years of age are at the greatest risk of scald burn injury. Caregiver burn prevention programs have been found to reduce the prevalence of injuries in young children; however, low-income and underserved populations seldomly have access to these programs. The impact of scald burn prevention programs in underserved populations remains unexplored. The objective of the current study was to evaluate the efficacy of a scald burn prevention program at a Level One Pediatric Trauma Center in a low-income, underserved community. Methods Our hospital developed a one-hour scald burn prevention program for caregivers with children 5 years of age or younger. The program educated caregivers on ways to prevent scald burns and create safeguards in their home. Caregivers completed a pre-post survey to measure their ability to identify hot or cold objects, as well as respond to items about their perceptions of the program’s utility, their willingness to share it with others, and the likelihood that they would use the information in the future. Data was analyzed using a paired t-test. Results Two-hundred and sixty-nine (N = 269) caregivers participated in the program. Before the program, caregivers could identify potentially hot objects 83.17% of the time, and after the program, they were able to identify these items 92.31% of the time: t (268) = 12.46, p d = 1.07. Additionally, 95% of caregivers indicated that the program was helpful, 99% stated that they were likely to share this information with others, and 100% indicated that they would use the information from the program. Conclusions Education is a critical component to prevent scald burns. Results indicate that a hospital-led scald burn prevention program can positively impact a caregiver’s ability to identify possible scald-burn risks. Providing education to caregivers who typically do not receive this information could lower the prevalence of scald burns not only institutionally, but in communities that are disproportionately impacted by this mechanism of injury.

Adjuvant chemoradiation (CRT), with high-dose cisplatin remains standard treatment for oral cavity squamous cell carcinoma (OCSCC) with high-risk pathologic features. We evaluated outcomes associated with different cisplatin dosing and schedules, concurrent with radiation (RT), and the effect of cumulative dosing of cisplatin. An IRB-approved collaborative database of patients (pts) with primary OCSCC (Stage I–IVB AJCC 7th edition) treated with primary surgical resection between January 2005 and January 2015, with or without adjuvant therapy, was established from six academic institutions. Patients were categorized by cisplatin dose and schedule, and resultant groups compared for demographic data, pathologic features, and outcomes by statistical analysis to determine disease free survival (DFS) and freedom from metastatic disease (DM). From a total sample size of 1282 pts, 196 pts were identified with high-risk features who were treated with adjuvant CRT. Administration schedule of cisplatin was not significantly associated with DFS. On multivariate (MVA), DFS was significantly better in patients without perineural invasion (PNI) and in those receiving ≥200 mg/m2 cisplatin dose (p &lt, 0.001 and 0.007). Median DFS, by cisplatin dose, was 10.5 (&lt, 200 mg/m2) vs. 20.8 months (≥200 mg/m2). Our analysis demonstrated cumulative cisplatin dose ≥200 mg/m2 was associated with improved DFS in high-risk resected OCSCC pts.

Objectives: To assess risk factors and non-thyroid specific postoperative complications for thyroid lobectomy compared to total thyroidectomy. Methods: A retrospective, cross-sectional study of adults undergoing a lobectomy or total thyroidectomy using the National Surgical Quality Improvement Program database between 2005 and 2017. Patients not treated by otolaryngologists or general surgeons and with unknown demographic variables were excluded. Results: A total of 106 915 patients were analyzed, 64 763 total thyroidectomies and 42 152 lobectomies. Multivariable analysis demonstrated that total thyroidectomy patients were half as likely to return to the operating room (OR = 0.491 (95%CI 0.445-0.542), P Conclusions: Our multi-institutional study indicates specific risk factors for returning to the operating room that may warrant closer follow up after surgery for total thyroidectomy or thyroid lobectomy. We also identified the most common post-operative complications. During pre-operative planning, these findings should be considered by thyroid surgeons to help mitigate risk to patients.

Background De-intensified treatment strategies for early human papillomavirus-positive (HPV+) oropharynx cancer (OPC) rely on selecting patients with an excellent prognosis. The criterion for enrollment in current de-intensification trials is ≤10 pack-years. More nuance to the pack-year criteria may expand enrollment, improve patient outcomes, and prevent overtreatment. It was hypothesized that patients with more than 10 pack-years may experience favorable outcomes if smoking cessation has been achieved. Methods From an institutional review board-approved database, patients with HPV+ oropharyngeal squamous carcinoma treated definitively with radiation with or without chemotherapy were retrospectively identified. Patients with a history of smoking who were eligible for national de-intensification trials were included (cT1-2N1-2b or T3N0-2b [American Joint Committee on Cancer, seventh edition]). Cox regression with penalized smoothing splines was used to evaluate nonlinear effects of cessation. Recursive partitioning analysis (RPA) was used to objectively search for relationships between the 2 colinear variables (pack-years and time since cessation). Results Among 330 patients meeting the inclusion criteria, 130 (40%) were never smokers, 139 (42%) were former smokers, and 61 (18%) were current smokers. With standard therapy, all former smokers achieved a progression-free survival (PFS) rate higher than 91%, regardless of pack-year exposure. Nonlinear Cox regression demonstrated that more recent cessation was associated with significantly worse PFS even among those with ≤20 pack-years. RPA demonstrated that only current smokers experienced a 2-year PFS rate lower than 91%; former smokers, regardless of pack-years, experienced a 2-year PFS rate higher than 91%. Conclusions The 10-pack-year rule may not apply to all early HPV+ OPCs, particularly for former smokers. Future randomized de-intensification trials should consider a broader and more nuanced approach until the predictive role of smoking status is established.

Poorly differentiated thyroid cancer (PDTC) is a rare but aggressive subtype of thyroid cancer that portends a poor prognosis. There remains a paucity of literature on PDTC outcomes. The aim of our study was to evaluate outcomes of PDTC in our tertiary care facility.We identified all histologically confirmed PDTC cases from 1997-2018 treated at our Institution and collected data points in an IRB-approved registry. We then conducted a retrospective study to assess outcomes and identified factors associated with inferior outcomes.Twenty-three patients were identified with a median age at diagnosis of 60 years (range=39-89 years). Nineteen (83%) underwent total thyroidectomy. Eight (42%) patients had lymph node dissections and 2 (11%) underwent adjuvant radiation. Thirteen (68%) patients were treated with radioactive iodine (RAI). Those who underwent total thyroidectomy had a median overall survival (mOS) of 88 months, 5 year-OS of 56%, 5 year-local recurrence-free survival (LRFS) of 45%, and 5 year-distant recurrence-free survival (DRFS) of 36%. T4 disease had worse mOS (14 vs. 87 m, p=0.0082), and 5 year-LRFS rate (12 vs. 74%, p=0.0312) compared to T1-3. N0 disease had an improved mOS (172 vs. 32 m, p=0.0013), 5 year-LRFS rate (63 vs. 17%, p=0.0033), and 5 year-DRFS (57 vs. 0%, p=0.0252). Eight out of 23 patients (35%) were alive at last follow-up, with a median of 68 months (range=20-214). The most common cause of death was distant recurrence (73%). Six patients received systemic therapy with various tyrosine kinase inhibitors with a median duration on treatment of 7 months (range=1-30 months).Advanced T and N stage were factors associated with significantly inferior outcomes. While select patients benefited with systemic treatment, it remains unclear if intensified locoregional therapy should be considered in patients with PDTC.

Investigate outcomes following oral cavity and oropharyngeal salvage surgery.Adult patients who underwent salvage surgery for recurrent squamous cell carcinoma of the oral cavity and oropharynx from 1996 to 2018 were analyzed using multivariable Cox proportional hazards regression. Disease-free survival (DFS), overall survival (OS), associated factors, and basic quality measures were analyzed.One hundred and eight patients (72% oral cavity, 28% oropharynx) were followed for a median of 17.9 months. Median DFS and OS were 9.9 and 21 months, respectively. Surgery with adjuvant chemoradiotherapy compared to surgery alone (hazard ratio [HR] = 0.15, 95% confidence interval [CI]: 0.03-0.78) and negative margins (HR = 0.36, 95% CI: 0.14-0.90) were associated with better DFS, while lymphovascular space invasion (LVSI) (HR = 2.66, 95% CI: 1.14-6.19) and higher stage (III vs. I-II, HR = 3.94, 95% CI: 1.22-12.71) were associated with worse DFS. Higher stage was associated with worse OS (HR = 3.79, 95% CI: 1.09-13.19). Patients were hospitalized for a median of 8 days with 24% readmitted within 30 days. A total of 72% and 38% of patients, respectively, underwent placement of a feeding tube or tracheostomy.After oral cavity and oropharyngeal salvage surgery, adjuvant chemoradiotherapy, negative margins, negative LVSI, and lower stage were associated with a lower risk of recurrence. Only lower-stage disease was associated with improved survival. The majority of patients had feeding tubes, half underwent free tissue transfer, a third required tracheostomy, and a quarter was readmitted.3 Laryngoscope, 132:1984-1992, 2022.

BACKGROUND/AIM Head and neck cancers are often treated with extended courses of radiotherapy (RT), which may prove excessively toxic for frail patients. Split course RT (SCRT) delivers two courses of RT separated by 4-6 weeks, personalizing treatment intensity based on response. In this study, we present our updated experience using this technique. PATIENTS AND METHODS From a single institution database, we identified patients considered for SCRT. For patients undergoing a second course of RT, cumulative incidence of locoregional recurrence (LRR) and overall survival (OS) are reported. RESULTS A total of 98 patients were included, of whom seventy-five percent underwent a second course of RT. The most common fractionation was 30 Gy in 10 fractions for each course, with a median cumulative dose of 60 Gy. In those undergoing a second course of RT, median OS was 9.7 months and cumulative incidence of LRR at 6, 12, and 24 months was 17.0%, 23.1%, and 29.4%, respectively. CONCLUSION SCRT offers an attractive treatment paradigm to personalize radiation intensity based on patient tolerance, while maintaining reasonable safety and efficacy in those unfit for standard full course RT.

Significance Statement Pharyngeal fistulas to the cervical spine resulting in vertebral osteomyelitis are a rare, yet clinically important, complication of total laryngectomy performed in conjunction with chemoradiotherapy or radiation therapy. This complication is likely underdiagnosed and can have a high mortality rate. It is very important that clinicians are aware of this complication as early diagnosis and management may improve patient outcomes.

To investigate the association between tumor volume and locoregional failure (LRF) after concurrent chemoradiation (CCRT) for locally advanced larynx cancer (LC).This is a retrospective cohort study from 2009 to 2014 identified from an institutional review board-approved registry. Fifty-nine of 68 patients with locally advanced larynx cancer treated with definitive CCRT who had available imaging for review were identified. The main endpoint to be assessed was the association between gross tumor volumes (GTV; T = total, P = primary, N = nodal) and LRF. Receiver operative characteristic (ROC) curves were used to investigate diagnostic accuracy.Twenty LRFs were observed, resulting in a 2-year LRF rate of 39% (95% CI, 23-52%). On UVA, the GTV-T (P = .01), GTV-P (P = .05), and GTV-N (P = .04) were statistically significant predictors of LRF. Furthermore, age, smoking status, N-stage, larynx subsite, and tracheostomy/feeding tube dependence were potentially associated with LRF (P .3), whereas T-stage (T3-4 vs. T2) was not (HR 1.05, 95% CI, 0.38-2.91, P = .92). In the multivariable model, GTV-P (HR 1.022, 95% CI, 0.999-1.046, P = .07) and GTV-N (HR 1.053, 95% CI, 1.0004-1.108, P = .05) were the two most impactful covariates on the model's RGTV is associated with LRF after definitive CCRT for LC. Patients with bulky primary and/or nodal tumors may be better served with upfront surgical resection regardless of T-stage. Further investigation into the safety of larynx preservation for low-volume T4 tumors can be considered.4 Laryngoscope, 130:2372-2377, 2020.

BACKGROUND We investigated the impact of level I lymph node involvement (LNI) on survival for patients with oropharyngeal squamous cell carcinoma (OPSCC). METHODS We performed a cohort study of patients with OPSCC who underwent resection with known human papillomavirus (HPV) status in the National Cancer Database (2010-2014). RESULTS Among 5591 patients with OPSCC, 599 (10.7%) had level I LNI. Predictors of level I LNI included pT classification (pT3 vs pT1; odds ratio [OR], 1.95; P

Purpose/Objective(s) The outcomes of second primary head and neck malignancies in survivors of HPV associated OPSCC treated with radiation have not been well documented. The purpose of this study was to review the rate, management, and outcomes of non-metastatic second head and neck malignancies in patients with a history of HPV positive OPSCC treated with definitive or postoperative radiation (RT). Materials/Methods This is a single institution IRB approved retrospective study of patients with HPV positive OPSCC treated from 2001-2017 with definitive radiation and at least 3 years of follow up. Diagnoses were considered to be a second head and neck malignancy if they were distinct from index OPSCC with the exclusion of a primary or regional recurrence, primary site > 2 cm from the index OPSCC, and occurred at least 2 years from prior RT. Patients with second malignancies involving the thyroid were excluded. Actuarial analysis was used to calculate overall survival and disease control rates. Results There were a total of 418 patients who met inclusion criteria with a median follow up of 88.5 months (50.9-150.9 months). A total of 11 patients (2.6%) developed a second primary malignancy in the head and neck (2 larynx, 1 nasal cavity, 6 oral cavity and 2 oropharynx) and all were treated with definitive surgery. Median time between first and second cancers was 73 months (25-123 months). Median follow up for these patients was 25.4 months (7.7-69 months) and the median age at second malignancy was 65 years (range 54-73 years). 64% of patients were former smokers (quit > 3 months) and 36% were never smokers. Pathological tumor stage of the second cancer was T1 in 36%, T2 in 27%, T4a in 36%. The histology was squamous cell carcinoma in 9 patients, spindle cell squamous carcinoma in 1 patient, and adenosquamous carcinoma 1 patient. HPV status was negative in 45.5%, positive in 18.2% and unknown in 36.4%. Post-operative re-irradiation was given in 55%, of which 50% received concurrent chemotherapy. Locoregional control rates at 12 and 24 months were 100% and 62.5% (95% CI: 28.9-96.1%), respectively. Of the 2 patients with local failure, which occurred at 18 and 33 months after diagnosis, salvage therapy with surgery was successful. Regional failure was diagnosed in 2 patients at 13 and 16 months after diagnosis, and both of these patients ultimately died as a result of regional failure. There were no distant failures. One additional patient had died at last follow up which was unrelated to cancer. Estimated 2-year overall survival from the second head and neck malignancy was 78.9% (95% CI: 53.0-100%). Conclusion The risk of a second head and neck malignancy in survivors of HPV associated OPSCC is low, but as the incidence of HPV related OPSCC remains elevated and the likelihood of cure is excellent, secondary malignancy is an important long-term risk. Despite prior RT, consideration of post-operative re-irradiation is important as regional failure may carry a poor prognosis.

Objectives The importance of treating the bilateral neck in lateralized small oral cavity squamous cell carcinoma (OCC) is unclear. We sought to define the incidence and predictors of contralateral neck failure (CLF) in patients who underwent unilateral treatment. Materials and methods We performed a multi-institutional retrospective study of patients with pathologic T1-T2 (AJCC 7th edition) OCC with clinically node negative contralateral neck who underwent unilateral treatment with primary surgical resection ± adjuvant radiotherapy between 2005 and 2015. Incidence of CLF was estimated using the cumulative incidence method. Clinicopathological factors were analyzed by univariate (UVA) and multivariate analysis (MVA) for possible association with CLF. Kaplan-Meier analysis was used to estimate overall survival (OS). Results 176 patients were evaluated with a median of 65.9 months of follow-up. Predominant pathologic T-stage was T1 (68%), 8.5% of patients were N1, 2.8% were N2b. Adjuvant radiotherapy was delivered to 17% of patients. 5-year incidence of CLF was 4.3% (95% CI 1.2–7.4%). Depth of invasion (DOI) > 10 mm and positive ipsilateral neck node were significant predictors for CLF on UVA. DOI > 10 mm remained significant on MVA (HR = 6.7, 95% CI 1.4–32.3, p = 0.02). The 2- and 5-year OS was 90.6% (95% CI 86.2–95.0%) and 80.6% (95% CI 74.5–86.8%), respectively. Conclusion Observation of the clinically node negative contralateral neck in small lateralized OCC can be a suitable management approach in well selected patients, however caution should be applied when DOI upstages small but deeply invasive tumors to T3 on 8th edition AJCC staging.

Objectives: To analyze characteristics, treatment outcomes, and prognostic factors of sarcomatoid squamous cell carcinoma of the head and neck. Study Design: Retrospective chart review. Setting: Tertiary care center. Subjects and Methods: Fifty-five patients were treated for sarcomatoid squamous cell carcinoma of the head and neck between 1996 and 2018. Data collection included clinical history, tumor characteristics, pathology, treatment modality, and outcomes. Mean follow up was 17.1 months. Cox univariate analysis was used to evaluate for associations with locoregional recurrence, distant metastasis, and overall survival. Results: Most patients were white males with a smoking history and median age 66 years (range 41-92) at diagnosis. Twenty-two percent had prior head and neck radiation. Tumor site was most frequently oral cavity (41.8%), followed by larynx (29.1%), and oropharynx (16.4%). Half presented with early T stage disease (15.5% T0, 12.7% T1, 30.9% T2) and the remainder with late stage disease (16.4% T3, 34.5% T4). Locoregional recurrence rate was 60.0%, metastatic recurrence was rate 21.8%, with median time to recurrence of 4 months and mean overall survival of 20 months. Presence of lymphovascular space invasion was statistically associated with locoregional recurrence ( P = .018, HR 3.55 [95% CI 1.24, 10.14]) and poorer overall survival ( P = .015, HR 2.92 [95% CI 1.23, 4.80]). Treatment with multimodality therapy was associated with decreased locoregional recurrence ( P = .039, HR 0.39 [95% CI 0.16, 0.95]) but did not impact overall survival. Conclusion: Sarcomatoid squamous cell carcinoma remains a rare and aggressive disease variant with high recurrence rates and high mortality. High risk features such as lymphovascular space may indicate the need for more aggressive therapy.

To characterize and assess the non-thyroid-specific postoperative complications of completion thyroidectomy as compared with total thyroidectomy.Retrospective analysis: 2005 to 2017.National Surgical Quality Improvement Program database.Patients aged18 years receiving a completion or total thyroidectomy were eligible for inclusion. Patients not treated by otolaryngologists or general surgeons and with unknown demographic variables were excluded.A total of 70,638 patients were analyzed, representing 64,763 total thyroidectomies and 5875 completion thyroidectomies. The 30-day mortality rate was 0.1% for both procedures (National data suggest that total and completion thyroidectomies are relatively safe procedures but that completion thyroidectomies are associated with lower rates of postoperative complications. These findings may play a role in determining treatment plans for patients and optimizing risk reduction.

BACKGROUND Postoperative radioactive iodine (RAI) administration is widely utilized in patients with differentiated thyroid cancer. While beneficial in select patients, it is critical to recognize the potential negative sequelae of this treatment. The prevention, diagnosis, and management of the salivary and lacrimal complications of RAI exposure are addressed in this consensus statement. METHODS A multidisciplinary panel of experts was convened under the auspices of the American Head and Neck Society Endocrine Surgery and Salivary Gland Sections. Following a comprehensive literature review to assess the current best evidence, this group developed six relevant consensus recommendations. RESULTS Consensus recommendations on RAI were made in the areas of patient assessment, optimal utilization, complication prevention, and complication management. CONCLUSION Salivary and lacrimal complications secondary to RAI exposure are common and need to be weighed when considering its use. The recommendations included in this statement provide direction for approaches to minimize and manage these complications.

The objective of this study is to evaluate locoregional and distant failure for human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) using American Joint Committee on Cancer eighth edition (AJCC 8) staging.Retrospective cohort study of 457 patients with HPV + OPSCC, treated with platinum-based chemoradiation from 2002 to 2018, followed for a median of 4.3 years. Time to locoregional failure (TTLRF) and distant failure (TTDF) were estimated by Kaplan-Meier method. Log-rank, recursive partitioning analysis (RPA), and multivariable Cox proportional hazards were used to evaluate associated factors and stratify risk.Rates of five-year locoregional control (LRC) and distant control (DC) were 92% (95% CI, 90-95%) and 89% (95% CI, 85-92%), respectively. Smoking, T4, N3, and stage III were associated with significantly worse TTLRF. RPA identified three distinct locoregional failure groups: cT1-3 and 19 pack-years vs. cT1-3 with ≥19 pack-years vs. cT4 (five-year LRC: 97% vs. 90% vs. 82%, P .0001). The only factor associated with significantly worse TTDF was smoking status, while stage was not correlated. RPA identified two prognostic groups: former or never smokers vs. current smokers (five-year DC: 92% vs. 77%, P = .0003).In the largest evaluation of HPV + OPSCC after platinum-based chemoradiation using AJCC 8, risk for locoregional recurrence was stratified by smoking, T category, N category, and overall stage. Risk of distant recurrence was only stratified by smoking status and not related to stage. This has implications for surveillance and clinical trial design.

Background/aim To assess factors that predict detection of tumors and oncologic outcomes in head and neck squamous cell carcinoma of unknown primary (SCCUP). Patients and methods This was a retrospective cohort study at a single tertiary care institution. Results The primary site was detected at examination under anesthesia (EUA) in 92 (51.1%) patients. The primary site was detected by directed biopsies in 60 (65%), palatine tonsillectomy in 28 (30.4%), and lingual tonsillectomy in 4 patients (4.3%). Four of eight lingual tonsillectomies were positive (50%). Primary locations included: palatine tonsils (51, 28.3%), base of tongue (37, 20.6%), larynx (4, 2.2%), oral cavity (3, 1.67%) and nasopharynx (1, 0.6%). Human papillomavirus (HPV) positive status (HR=0.26, p=0.004) and treatment with chemoradiation (CRT) (HR=0.38, p=0.004) were associated with better disease free survival (DFS). Conclusion A primary site was located after aggressive investigation in approximately half of the patients. More research is warranted towards the use of lingual tonsillectomy. Predictors of favorable prognosis included HPV positive status and treatment with CRT.

Objective: In the Amish community, natural therapies, such as Burns and Wounds (B&W) ointment and burdock leaves, are preferred over modern medicine when treating burn wounds. The primary aim of this case series is to highlight the use and clinical outcomes of this treatment for paediatric Amish patients. Method: At the a paediatric burn centre, two patients were treated with B&W ointment and burdock leaves. The first patient was 11 months old with 17% total body surface area (TBSA) partial and full-thickness scald burns to her lower extremities. The second patient was 24 months old with 20% TBSA partial-thickness scald burns to the torso, bilateral upper extremities, neck and chin. Results: Soon after presentation to the hospital, both patients developed positive wound cultures and required cessation of ointment and burdock leaf therapy. Both patients ultimately underwent surgical interventions. Conclusion: Managing burn wounds with B&W ointment and burdock leaves should be considered as an additional option for wound care in select cases. However, the efficacy of this therapy is limited and standard-of-care modern medical burn treatments should remain an option for these patients. It is critically important to build a mutually respectful relationship with Amish patients' community leaders, as this allows open communication and collaboration in patient care and increases the likelihood that Amish guardians will bring their children to a hospital when necessary.

Objectives Patients with human papillomavirus (HPV) associated squamous cell carcinoma of the oropharynx (SCC-OP) have improved overall survival (OS) after distant metastasis (DM) compared to HPV negative patients. These patients may be appropriate candidates for enrollment on clinical trials evaluating the efficacy of metastasis-directed therapy (MDT). This study seeks to identify prognostic factors associated with OS after DM, which could serve as enrollment criteria for such trials. Materials and methods From an IRB approved multi-institutional database, we retrospectively identified patients with HPV/p16 positive SCC-OP diagnosed between 2001 and 2018. Patterns of distant failure were assessed, including number of lesions at diagnosis and sites of involvement. The primary outcome was OS after DM. Prognostic factors for OS after DM were identified with Cox proportional hazards. Stepwise approach was used for multivariable analysis. Results We identified 621 patients with HPV-associated SCC-OP, of whom 82 (13.2%) were diagnosed with DM. Median OS after DM was 14.6 months. On multivariable analysis, smoking history and number of lesions were significantly associated with prolonged OS. Median OS after DM by smoking (never vs ever) was 37.6 vs 11.2 months (p = 0.006), and by lesion number (1 vs 2–4 vs 5 or more) was 41.2 vs 17.2 vs 10.8 months (p = 0.007). Conclusion Among patients with newly diagnosed metastatic HPV-associated SCC-OP, lesion number and smoking status were associated with significantly prolonged overall survival. These factors should be incorporated into the design of clinical trials investigating the utility of MDT, with or without systemic therapy, in this population.

OBJECTIVES/HYPOTHESIS Evaluate the impact and accuracy of clinical laryngeal cancer staging. STUDY DESIGN Retrospective cohort study. METHODS Two hundred sixty-five consecutive patients with laryngeal squamous cell carcinoma who underwent total laryngectomy from 2001 to 2017 were studied. Clinical versus pathologic tumor (T) and nodal (N) categories were compared. Logistic regression and Cox proportional hazards analyzed the association of stage change with perioperative factors and outcomes. RESULTS Forty-seven patients (17.7%, accuracy = 0.969 ± 0.010 [standard error]) changed between T1-2 and T3-4. Sixty-four patients (24.1%, accuracy = 0.866 ± 0.020) had inaccurate N category. Salvage patients were less likely to have stage change (downstage: odds ratio [OR] = 0.20, 95% confidence interval [CI]: 0.08-0.50, P

The etiology of head and neck squamous cell carcinoma (HNSCC) is not fully understood. While risk factors such as positive human papilloma virus (HPV) status, smoking and tobacco use have been identified, they do not account for all cases of the disease. We aimed to characterize the bacteriome, mycobiome and mycobiome-bacteriome interactions of oral wash in HNSCC patients and to determine if they are distinct from those of the oral wash of matched non-HNSCC patients. Oral wash samples were collected from 46 individuals with HNSCC and 46 controls for microbiome analyses. We identified three fungal phyla and eleven bacterial phyla of which Ascomycota (fungi, 72%) and Firmicutes (bacteria, 39%) were the most dominant, respectively. A number of organisms were identified as being differentially abundant between oral wash samples from patients with HNSCC and oral wash samples from those without HNSCC. Of note, strains of Candida albicans and Rothia mucilaginosa were differentially abundant and Schizophyllum commune was depleted in those with HNSCC compared to oral wash from those without HNSCC. Our results suggest that the oral cavity of HNSCC patients harbors unique differences in the mycobiome, bacteriome, and microbiome interactions when compared to those of control patients.

Background: Process-related measures have been proposed as quality metrics in head and neck cancer care. A recent single-institution study identified four key metrics associated with increased survival. This study sought to validate the association of these quality metrics with survival in a multi-institutional cohort. Methods: Multicenter retrospective study of patients with oral cavity squamous cell (1/2005-1/2015). Baseline patient and disease characteristics and compliance with quality metrics was evaluated. Association between compliance with quality metrics with overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) was evaluated using Cox proportional hazards models. Results: Failure to comply with two or more of the quality metrics was associated with worse OS, DFS, and DSS. Adherence to all or all but one of the quality metrics was found to be associated with improved survival. Conclusions: Process-related quality metrics are associated with increased survival in patients with oral cavity squamous cell carcinoma in a multi-institutional cohort.

To explore the influence of treatment package time(TPT) in high-risk oral cavity squamous cell carcinoma(OCSCC) receiving adjuvant radiotherapy with concurrent chemotherapy(CRT).We queried our multi-institutional OCSCC collaborative database for cases diagnosed between 2005 and 2015 who underwent surgery followed by adjuvant CRT. All patients had high-risk features: extranodal extension(ENE) and/or positive surgical margin(PM). TPT was days between surgery to last radiotherapy fraction. Kaplan-Meier curves, log-rank p-values and multivariate analysis(MVA) were used to investigate the impact of TPT on overall(OS), disease-free(DFS), locoregional failure-free(LRFS) and distant metastases-free(DMFS) survival.We identified 187 cases: median age 58 (range, 24-87 years), males 66%, and ever smokers 69%. ENE and PM were detected in 85% and 32%, and oral tongue and floor of the mouth constituted 49% and 18%, respectively. Median radiotherapy and cisplatin doses received were 66 Gy and 200 mg/m2. Overall, median TPT was 98 (range, 63-162 days). OS was worse for TPT 90-days (n = 134) than TPT ≤ 90 (n = 53) at two-(65% vs. 71%) and five-years (45% vs. 62%); p = 0.05, with similar results for DFS. No influence on LRFS or DMFS was noted. More lymph nodes(LN) dissected(P = 0.039), T3-4 disease(P = 0.017), and unplanned reoperations(P = 0.037) occurred with TPT 90-days. On MVA, TPT in 10-day increments was independently detrimental for OS (Hazard Ratio: 1.14; 95 %Confidence Interval [1-1.28]; P = 0.043), perineural invasion, age and positive LN (p 0.05 for all).In one of the largest multi-institutional cohorts, TPT 90-days predicted worse OS for high-risk OCSCC receiving adjuvant CRT. All efforts are needed to optimize perioperative care and baseline conditions for favorable outcomes.

Eagle syndrome, a spectrum of disease resulting from an elongated styloid process and/or calcified stylohyoid ligament, lacks standardized recommendations regarding indications for surgical intervention and approach.Retrospective cohort study.Single tertiary care institution.Patients treated surgically for Eagle syndrome between January 2011 and June 2017.Patients were diagnosed with Eagle syndrome based on thorough clinical workup and assessment. The primary outcome was improvement in pain severity following surgery, with complete resolution of pain being considered clinically meaningful. Wilcoxon rank-sum tests and Fisher's exact were used to compare numerical and categorical variables, respectively.Twenty-one patients were diagnosed with Eagle syndrome and underwent surgical resection of the styloid process. Patients most often complained of neck pain (81%), throat pain (62%), and ear pain (48%). Among these patients, 57% of procedures featured a transcervical approach, while the remaining 43% were transoral. The vast majority (90%) of patients experienced improvement in pain severity from a median of 6.0 before surgery to 0.0 afterwards (p 0.01) as 62% experienced complete resolution. Using multivariable linear regression to model changes in pain severity, neck pain (β = -1.69, p 0.01) and jaw pain (β = -0.93, p = 0.03) predicted greater relief, while headache (β = 0.82, p = 0.04) predicted an inferior response. Adverse events were uncommon and typically resolved within three months, with 24% experiencing first bite syndrome and 19% reporting numbness.Transcervical and transoral styloidectomy are effective treatments for Eagle syndrome with minimal adverse effects. Patients with classic symptoms of neck or jaw pain benefit most from surgery.

Objectives/hypothesis Case reports of a painful variant of Hashimoto's thyroiditis exist in the literature; however, these cases have only been documented in adult patients and there are no standard treatment guidelines. The aim of this study was to describe an alternative management for Hashimoto's thyroiditis associated with medically intractable head and neck pain in the pediatric population. Study design Case series with chart review. Methods The study was conducted in the Section of Pediatric Otolaryngology at the Cleveland Clinic. We retrospectively analyzed pediatric patients (ages 0-18 years) with painful thyroiditis and/or headache who underwent total thyroidectomy from 2005 to 2014 with a clinical diagnosis of Hashimoto's thyroiditis. A thorough chart review was performed, including medical and family history, presenting symptoms, laboratory values, medical and surgical treatment strategies, operative reports, and surgical pathology. Results There were 0.02% of patients (5 of 305) who met the criteria of intractable head and or neck pain. All five underwent total thyroidectomy with confirmation of Hashimoto's thyroiditis on surgical pathology. Surgical treatment resulted in complete cervical pain relief and improved headaches with a minimum follow-up of 36 months. Conclusions Hashimoto's thyroiditis is a relatively common form of autoimmune thyroiditis in pediatric patients that uncommonly results in intractable neck pain or headache. In this case series, thyroidectomy was an effective alternative treatment in the pediatric population for medical failures in chronic painful Hashimoto's thyroiditis. Level of evidence 4. Laryngoscope, 128:2213-2217, 2018.

BACKGROUND Time to treatment initiation (TTI) is increasing and is associated with worsening survival. In the current study, the authors sought to identify a mechanism for this relationship by assessing the effect of TTI on clinical-to-pathologic upstaging in patients with head and neck squamous cell carcinoma (HNSCC). METHODS Using the National Cancer Data Base, the authors analyzed patients receiving definitive surgery for SCC of the oral cavity, oropharynx, larynx, and hypopharynx from 2005 through 2014. The primary outcome was T, N, or stage group upstaging, defined as higher pathologic stage than clinical stage. TTI was defined as the time between diagnosis and surgery. Multivariable logistic and Cox proportional hazards regression modeled upstaging and survival, respectively. RESULTS Cohorts of 60,194 patients, 51,380 patients, and 52,980 patients, respectively, with complete T, N, and stage group data were included. N upstaging was most common (18.6%), followed by stage group (17.4%) and T (12.1%) upstaging; all types were predicted by TTI. Compared with a TTI of 1 to 6 days, TTIs as short as 7 to 13 days (odds ratio, 1.20; P = .038) or ≥ 70 days (odds ratio, 2.04; P

Purpose/objective(s) Hypofractionated intensity modulated radiation therapy (H-IMRT) is uncommonly used in head and neck cancers due to concern for toxicity. This study reviews our experience using H-IMRT for head and neck cancers and explores its tolerability and efficacy. Materials/methods This single institution IRB approved retrospective study includes patients with head and neck cancers treated with definitive or post-operative H-IMRT from 2011-2020. Patients treated with ≥50Gy in 20 fractions to the primary tumor site and/or neck with at least 3 months of follow up were included. Patients treated to a superficial target only without proximity to mucosal surfaces or coverage of the elective neck (e.g., scalp; skin only targets) were excluded. Patients undergoing re-irradiation were excluded. Toxicity was scored using CTCAE v4.0. Acute toxicity included events occurring within 90 days of H-IMRT completion. Late toxicities occurred any time thereafter. Multiple toxicities in the same patient were scored separately. Results Fifty-nine patients with a median follow up of 10.9 months (range 3.0-111.5) were included. The majority of patients were white (93%) and male (78%) with a median age of 79.1. The most common primary tumor sites were skin (42%), major salivary glands (22%), and oral cavity (9%). The most frequent histologies included squamous cell carcinoma (66%) followed by thyroid cancer (7%), melanoma (5%), and Merkel cell carcinoma (5%). Treatment was delivered post-operatively in 80% and definitively in 20% of patients. All patients were treated with ≥50 Gy in 20 fractions, with the most common dose being 50 Gy (53%) followed by 55 Gy (44%). In 64% of patients a secondary elective dose of 45-50 Gy was used. Site treated included primary tumor site/bed with unilateral neck (54%), primary tumor site/bed with bilateral neck (19%), primary tumor site/bed alone (14%), unilateral neck (8%), and bilateral neck (5%). Five patients (8%) experienced a locoregional failure at a median time of 5.4 months (range 2.8-13.9). There were no grade 4 or 5 toxicities. Ten patients (17%) experienced acute grade 3 toxicity including mucositis (12%) and dermatitis (5%). Forty-six patients (78%) had an acute grade 2 toxicity, most commonly dermatitis (41%), pain (32%), fatigue (32%), dysgeusia (31%) and xerostomia (22%). Five patients (8%) experienced grade 2 late complications including neck fibrosis in three patients and trismus, aspiration pneumonia, and osteoradionecrosis in one patient each. No patient experienced grade 3 or higher late toxicity. No patients required the placement of a feeding tube or tracheostomy. Conclusion Hypofractionated IMRT in the definitive or post-operative treatment of head and neck cancers using ≥50Gy in 20 fractions appears safe and well tolerated with modest toxicity. Prospective studies comparing the safety and efficacy of H-IMRT to conventionally fractionated IMRT are warranted.

Objectives/Hypothesis Patients with human papillomavirus (HPV)–induced cancer of unknown primary (CUP) are generally excluded from clinical trials, despite surgical series reporting detection rates of occult oropharynx primaries of >80%. We performed a matched-pair analysis to compare outcomes between T0N1-3M0 HPV+ CUP and T1-2N1-3M0 HPV+ oropharynx known primary (OPX). Study Design Retrospective cohort study at a single institution. Methods Patients with early T stage, node positive HPV+ OPX or CUP treated with curative intent between 1998 and 2016 were identified. For a subgroup of CUP patients with an unknown HPV status, we imputed HPV status and included patients with a >80% probability of being HPV+. Cohorts were matched based on patient demographics using a nearest neighbor propensity technique. After matching, patients were grouped according to either a favorable or unfavorable risk stratification designations per current NRG Oncology clinical trial enrollment criteria. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan-Meier analysis. Results Of 298 patients with T1-2N1-3 OPX, 48 were matched to 48 HPV+ CUP patients (32 with confirmed and 16 imputed HPV status). Median follow-up for CUP (34.1 months) and OPX (27.8 months) patients were similar (P = .23).There were no significant differences between the CUP and OPX groups for 3-year DFS (89% vs. 85%, P = .44), and 3-year OS (91% vs. 91%, P = .11), respectively. Conclusions Patients with T0N+M0 HPV-induced CUP have similar survival outcomes to matched patients with T1-2N+M0 HPV+ OPX. These patients can reasonably be included in clinical trials investigating the role of treatment deintensification and risk stratified similar to patients with early-stage known primary OPX cancer. Level of Evidence 4. Laryngoscope, 2017

// Pranab K. Mukherjee 1,* , Hannah Wang 2, 3, * , Mauricio Retuerto 1 , Huan Zhang 2, 3 , Brian Burkey 4, 7 , Mahmoud A. Ghannoum 1, 7, 8 and Charis Eng 2, 3, 4, 6, 8 1 Center for Medical Mycology, Department of Dermatology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA 2 Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA 3 Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA 4 Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA 5 Section of Head and Neck Surgery and Oncology, Head and Neck Institute, Cleveland Clinic, Cleveland, OH, USA 6 Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA 7 Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA 8 Germline High Risk Cancer Focus Group, CASE Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA * Contributed equally to the work and should be viewed as joint first authors Correspondence to: Charis Eng, email: engc@ccf.org Mahmoud A. Ghannoum, email: mag3@case.edu Keywords: microbiome; metagenomics; head and neck squamous cell carcinoma; lingual carcinomas Received: June 08, 2017 Accepted: September 08, 2017 Published: October 19, 2017 ABSTRACT Squamous cell carcinoma of the oral (mobile) tongue (OMTC), a non-human papilloma virus-associated oral cancer, is rapidly increasing without clear etiology. Poor oral hygiene has been associated with oral cancers, suggesting that oral bacteriome (bacterial community) and mycobiome (fungal community) could play a role. While the bacteriome is increasingly recognized as an active participant in health, the role of the mycobiome has not been studied in OMTC. Tissue DNA was extracted from 39 paired tumor and adjacent normal tissues from patients with OMTC. Microbiome profiling, principal coordinate, and dissimilarity index analyses showed bacterial diversity and richness, and fungal richness, were significantly reduced in tumor tissue (TT) compared to their matched non-tumor tissues (NTT, P

Purpose To determine the accuracy of intraoperative frozen section analysis on thyroidectomy specimens stratified by the Bethesda classification scheme and its utility for intraoperative decision-making. Study design Retrospective chart review. Methods A retrospective review was performed on all patients who underwent thyroidectomy or thyroid lobectomy with intraoperative frozen sections at a tertiary care academic center from 2009 to 2015. Results There were 74 total patients who underwent partial or total thyroidectomy with intraoperative frozen section analysis of a thyroid nodule whom had previously undergone a thyroid fine needle aspiration of the nodule. The sensitivity, specificity, positive predictive value, and negative predictive value for a thyroid frozen section with respect to its prediction for malignancy was 81%, 95%, 98%, and 66%, respectively, with a diagnostic accuracy of 85%. For 37 patients with an indeterminate cytologic diagnosis on fine needle aspiration (Bethesda categories III–V), the sensitivity, specificity, positive predictive value, and negative predictive value for a thyroid frozen section was 81%, 91%, 95%, and 67%, respectively, with a diagnostic accuracy of 84%. False positives and false negatives resulted in 1 completion thyroidectomy for benign pathology and 3 reoperations for malignancy not discovered on frozen section. Conclusion While intraoperative frozen sections on thyroid specimens may be helpful if positive, the false negative rate remains high. There appears to be limited value in routine frozen sections to guide clinical management and decision-making in the era of the Bethesda system.

Identifying prognostic risk factors and determining the efficacy of common surgical treatments is critical to determine optimal treatment strategies for patients with medullary thyroid carcinoma (MTC). The objective of this study was to review a contemporary institutional experience with MTC primary treatment with 2 goals: to identify prognostic factors that impact survival and to study the effect of neck dissection on those outcomes.This study was a retrospective case series of patients with MTC who underwent at least a total thyroidectomy with curative intent. Clinical parameters including tumor and nodal staging with corresponding pathology findings were identified. Survival endpoints included overall survival, disease-free survival, and biochemical cure.Sixty-seven patients were included. The majority presented with early T-stage disease. Fifty (76%) patients were N0 at presentation. Seventeen (24%) had some evidence of neck disease on clinical examination or imaging. Forty (71%) achieved biochemical cure, and the 5-year biochemical recurrence-free survival for those cases was 86.5%. Among patients who had successful resection of all gross disease, 92% had no evidence of structural disease at 5 years. Overall survival was 91% at 5 years. Increased pre-operative calcitonin (Ct) level, primary tumor size, extrathyroidal extension, and neck metastases decrease the rate of biochemical cure. Larger tumor size increases the risk of structural disease recurrence and biochemical relapse after initial cure. The presence and number of neck metastases correlate with biochemical relapse. The presence of lateral neck nodes (pN1b) does not have different survival implications than centrally confined disease (pN1a).This study shows increasing tumor size, increased Ct level, and cervical metastases are poor prognostic factors. Patients with large tumors, high Ct level, or unfavorable pathologic findings may warrant more aggressive initial treatment, although limitations of the study prevent any conclusion regarding the effect of neck dissection.ATA = American Thyroid Association BRFS = biochemical recurrence-free survival CND = central neck dissection Ct = calcitonin DFS = disease-free survival MTC = medullary thyroid carcinoma OR = odds ratio OS = overall survival pCND = prophylactic CND.

Background Metabolomics represents a promising approach for discovering novel targets and biomarkers in head and neck squamous cell carcinoma (HNSCC). Here we used metabolomics to identify oral metabolites associated with HNSCC. Methods Tumor and adjacent normal tissue from surgical resections and presurgical oral washes as well as oral washes were collected from healthy participants. Metabolites extractions of these samples were analyzed by liquid chromatography-mass spectroscopy (LC/MS), LC/MS/MS and gas chromatography-MS (GC/MS). Results Among 28 samples obtained from 7 HNSCC cases and 7 controls, 422 metabolites were detected (269 identified and 153 unidentified). Oral washes contained 12 and 23 metabolites in healthy controls and HNSCC patients, respectively, with phosphate and lactate being the most abundant. Small molecules related to energy metabolism were significantly elevated in HNSCC patients compared to controls. Levels of beta-alanine, alpha-hydroxyisovalerate, tryptophan, and hexanoylcarnitine were elevated in HNSCC oral washes compared to healthy controls (range 7.8-12.2-fold). Resection tissues contained 22 metabolites, of which eight were overproduced in tumor by 1.9- to 12-fold compared to controls. TCA cycle analogs 2-hydroxyglutarate (2-HG) and 3-GMP were detected exclusively in tumor tissues. Targeted quantification of 2-HG in a representative HNSCC patient showed increase in tumor tissue (14.7 μg/mL), but undetectable in normal tissue. Moreover, high levels of 2-HG were detected in HNSCC cell lines but not in healthy primary oral keratinocyte cultures. Conclusions Oral metabolites related to energy metabolism were elevated in HNSCC, and acylcarnitine and 2HG may have potential as non-invasive biomarkers. Further validation in clinical studies is warranted., Highlights • Metabolomics identified HNSCC-associated oral metabolites in tissues and oral wash. • Oral metabolites related to energy metabolism were elevated in HNSCC. • 2-hydroxyglutarate was detected in HNSCC tumor but not in adjacent normal tissues. • 2-hydroxyglutarate and acylcarnitine may have potential as non-invasive biomarkers.

Background Using the frameworks of transformational learning and situated learning theory, we developed a technology-enhanced professionalism curricular model to build a learning community aimed at promoting residents' self-reflection and self-awareness. The RAPR model had 4 components: (1) Recognize: elicit awareness; (2) Appreciate: question assumptions and take multiple perspectives; (3) Practice: try new/changed perspectives; and (4) Reflect: articulate implications of transformed views on future actions. Objective The authors explored the acceptability and practicality of the RAPR model in teaching professionalism in a residency setting, including how residents and faculty perceive the model, how well residents carry out the curricular activities, and whether these activities support transformational learning. Methods A convenience sample of 52 postgraduate years 1 through 3 internal medicine residents participated in the 10-hour curriculum over 4 weeks. A constructivist approach guided the thematic analysis of residents' written reflections, which were a required curricular task. Results A total of 94% (49 of 52) of residents participated in 2 implementation periods (January and March 2015). Findings suggested that RAPR has the potential to foster professionalism transformation in 3 domains: (1) attitudinal, with participants reporting they viewed professionalism in a more positive light and felt more empathetic toward patients; (2) behavioral, with residents indicating their ability to listen to patients increased; and (3) cognitive, with residents indicating the discussions improved their ability to reflect, and this helped them create meaning from experiences. Conclusions Our findings suggest that RAPR offers an acceptable and practical strategy to teach professionalism to residents.

Background Human papillomavirus (HPV)-positive oropharyngeal cancer is associated with favorable outcomes, prompting investigations into treatment deintensification. The purpose of this study was for us to present the predictors of distant metastases in patients with HPV-positive oropharyngeal cancer treated with cisplatin-based chemoradiotherapy (CRT) or cetuximab-based bioradiotherapy (bio-RT). Methods In patients with stage III to IVb HPV-positive oropharyngeal cancer, the Kaplan-Meier analysis was used to calculate distant metastases rates. Univariate analysis (UVA) and multivariate analysis (MVA) were used to identify factors associated with distant metastases. Results Increased distant metastases rates were noted in active smokers versus never/former smokers (22% vs 5%), T4 vs T1 to T3 (15% vs 6%), and cetuximab-based bio-RT versus CRT (23% vs 5%). All remained significant on MVA. Conclusion T4 tumors and active smokers have substantial rates of distant metastases, and trials investigating intensified systemic therapies may be considered. Higher rates of distant metastases observed with concurrent cetuximab are hypothesis generating, but further data are needed. © 2017 Wiley Periodicals, Inc. Head Neck 39: 940-946, 2017.

Several emerging sinonasal malignancies have recently been described in the pathology literature. Although not all distinctly classified by the World Health Organization, these rare tumors present a management challenge to surgeons and oncologists. While prior studies have summarized histologic details, a clinically focused review is currently lacking in the literature. This review describes the presentation, histopathology, imaging, treatment, and prognosis of newly described or recently evolving sinonasal malignancies while highlighting the distinguishing features of these entities. It includes teratocarcinosarcoma, human papillomavirus-related multiphenotypic carcinoma, biphenotypic sinonasal sarcoma, sinonasal renal cell-like adenocarcinoma, NUT-midline carcinoma, squamous cell carcinoma associated with inverted papilloma, sinonasal undifferentiated carcinoma, and INI-1-deficient sinonasal carcinoma. By describing the diagnosis, treatment, and prognosis of these recently defined entities, this clinical review aims to help guide oncologists in the clinical management of these patients.

Background The eighth edition of the American Joint Committee on Cancer staging manual (AJCC8) added depth of invasion to the definition of pathologic T stage (pT). In the current study, the authors assess pT stage migration and the prognostic performance of the updated pT stage and compare it with other clinicopathologic variables in patients with early squamous cell carcinoma of the oral tongue (OTSCC; tumors measuring ≤4 cm) with histologically benign lymph nodes (pN0). Methods A multi-institutional cohort of patients with early OTSCC was restaged as per AJCC8. Primary endpoints were local recurrence (LR) and locoregional recurrence (LRR). Influential variables were identified and an LR/LRR prediction model was developed. Results There were a total of 494 patients, with 49 LR and 73 LRR. AJCC8 pT criteria resulted in upstaging of 37.9% of patients (187 of 494 patients), including 34.5% (64 of 185 patients) from pT2 to pT3, without improving the prognostication for LR or LRR. Both LR and LRR were found to be similar for patients with AJCC8 pT2 and pT3 disease. On multivariate analysis, LR was only found to be associated with distance to the closest margin (hazard ratio, 0.36; 95% CI, 0.20-0.64 [P = .0007]) and perineural invasion (hazard ratio, 1.92; 95% CI, 1.10-0.64 [P = .046]). Based on these 2 predictors, a final proportional hazards regression model (which may be used similar to a nomogram) was developed. The proposed model appeared to be superior to AJCC pT stage for estimating the probability of LR and LRR for individual patients with early OTSCC. Conclusions AJCC8 pT criteria resulted in pT upstaging of patients with pN0 disease without improved LR or LRR prognostication. The proposed model based on distance to the closest margin and perineural invasion, status outperformed pT as a predictor of LR and LRR in patients with early OTSCC.

PURPOSE: To determine which factors influence cost in head and neck cancer (HNC) to inform the development of a bundled payment model (BPM). METHODS: Patients with stages 0 to IVB (by American Joint Commission on Cancer, 7th edition) HNC of various sites and histology treated definitively at a single tertiary care center during 2013 were included. Clinical variables and direct cost data were obtained, and their associations were investigated using χ2, t, Wilcoxon rank sum, and analysis of variance testing. Results were used to develop a BPM. RESULTS: One hundred fifty patients were included; 87% were white, 74% were men, 48% had oropharyngeal cancer, and 58% had stage IVA disease. Treatment consisted of surgery alone (17%), radiation alone (11%), surgery plus radiation (14%), chemoradiation (45%), and surgery plus chemoradiation (13%). On multivariable analysis, both increasing group stage and number of treatment modalities used were significantly associated with higher cost. Given that stage often dictates treatment, we developed three cost tiers that were based on overall treatment modality. Tier A, the least costly, consisted of single-modality therapy with either surgery alone or radiation alone (median cost divided by the median overall cost of treatment, 0.54; 25th to 75th percentile range, 0.29 to 1.02), followed by tier B, which consisted of bimodality therapy with either chemoradiation or surgery plus radiation (1.03; range, 0.81 to 1.35), followed by tier C, which consisted of trimodality therapy with surgery plus chemoradiation (1.43; range, 1.10 to 1.96). CONCLUSION: The number of treatment modalities required is the primary driver of cost in HNC. These data can simplify development of a comprehensive HNC BPM.

BACKGROUND The role of smoking among patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is unclear. METHODS A retrospective cohort study of patients with HPV(+) OPSCC from 2001 to 2015 at a tertiary-care institution was conducted. The primary outcome was overall survival (OS). RESULTS Among 484 included patients, 94 (19.4%) were active smokers, 226 (46.7%) were former smokers, and 164 (33.9%) never smoked. Among active smokers, 82 patients (87.2%) had a ≥10 pack-year and 69 (73.4%) had a ≥20 pack-year smoking history. After adjusting for covariates, active smoking was a significant predictor of inferior OS (HR 2.28, P

Nonthyroid metastases to the thyroid gland can cause morbidity, including dysphagia, dysphonia, and airway compromise. Because metastatic malignancies portend a poor prognosis, obtaining equipoise between treatment morbidity and local disease progression is paramount. We reviewed cases of nonthyroid metastases to determine treatment and prognostic recommendations.Case series with chart review.Tertiary care hospital.We searched PubMed for reported cases between 1994 and September 2013 using search terms as follows: any combination of primary tumor locations and thyroid, as well as the terms thyroid and metastasis. Only unique cases of nonthyroid metastases were included. Combined with 17 additional tumors at our own institution, we found 818 unique nonthyroid metastases, of which 384 had management and survival data available.Renal cell carcinoma was most common, presenting in 293 (35.8%) patients, followed by lung and gastrointestinal malignancies. Patients were treated with total thyroidectomy (34.0%), subtotal thyroidectomy including lobectomy (32.6%), and no surgery (33.5%). Surgical management was associated with improved survival duration (P.01). Locoregional recurrence was less likely in patients treated with total versus partial thyroidectomy (4.8% vs 13%). Extent of surgical management did not have a significant effect on patient survival. Delayed presentation was associated with improved survival duration (P = .01).Nonthyroid metastases to the thyroid gland are unusual tumors. Surgical intervention is associated with improved survival, but expected morbidity of untreated tumors is difficult to assess. Site of origin, time to diagnosis, and surgical approach are related to survival and recurrence rates.

Background T2 glottic cancer with impaired vocal cord mobility (T2b) is known to have higher local failure rates when compared with T2 cancers without impaired cord mobility (T2a) treated with radiotherapy (RT) alone. Methods In this retrospective review, we identified and compared the local control rates of 3 groups: T2aN0 treated with RT; T2bN0 treated with RT; and T2b-3N0-2 treated with chemoradiotherapy (CRT). Results The 3-year local control rate was 95.1% for T2aN0, 73.2% for T2bN0 treated with RT, and 91.5% for the CRT group (p = .01). On univariate analysis, T2bN0 disease versus T2aN0 treated with RT alone (p = .03) was significantly associated with inferior local control. Conclusion Patients with glottic cancer with impaired vocal cord mobility (T2b) have a high rate of local failure with RT alone. The addition of concurrent chemotherapy should be considered for patients highly motivated toward larynx preservation and willing to accept the potential toxicity. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

Summary Purpose The long-term results of RTOG 91-11 suggested increased deaths not attributed to larynx cancer after concomitant chemoradiotherapy (CRT) despite no apparent increase in late effects. Because the timing of events was not reported by RTOG 91-11, one possibility is that severe late dysphagia (SLD) develops beyond five years and leads to unreported treatment-related deaths. Here we explore the timing of SLD after CRT. Methods Patients who would have met eligibility criteria for RTOG 91-11 and were treated with CRT between 1993 and 2013 were identified. Events occurring beyond 3 months after treatment and suggestive of SLD were recorded including esophageal stricture dilations, hospital admissions for aspiration pneumonia or feeding-tube insertion. Feeding-tube dependence beyond one year was also considered SLD. The cumulative incidence of SLD and its components was quantified using Gray’s competing risk analysis with recurrence or death considered competing risks. Results Eighty-four patients were included with a median follow-up of 43 months. The 5-year overall survival was 70% (95% CI 58–80%). No death was directly a result of treatment-induced late dysphagia. The 5-year incidence of SLD was 26.5%. While 15 of 18 (83%) first stricture dilations occurred within 5 years after CRT, 3 of 5 (60%) aspiration admissions and 5 of 8 late feeding tube insertions occurred beyond five years from CRT. Conclusions SLD is common after CRT for larynx cancer and can occur beyond 5 years from the end of treatment, emphasizing the importance of survivorship follow-up. Despite the incidence of SLD, death related to dysphagia is uncommon.

Human papillomavirus-related (HPV+) oropharyngeal cancer is a rapidly emerging disease with generally good prognosis. Many prognostic algorithms for oropharyngeal cancer incorporate HPV status as a stratification factor, rather than recognising the uniqueness of HPV+ disease. The International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) aimed to develop a TNM classification specific to HPV+ oropharyngeal cancer.The ICON-S study included patients with non-metastatic oropharyngeal cancer from seven cancer centres located across Europe and North America; one centre comprised the training cohort and six formed the validation cohorts. We ascertained patients' HPV status with p16 staining or in-situ hybridisation. We compared overall survival at 5 years between training and validation cohorts according to 7th edition TNM classifications and HPV status. We used recursive partitioning analysis (RPA) and adjusted hazard ratio (AHR) modelling methods to derive new staging classifications for HPV+ oropharyngeal cancer. Recent hypotheses concerning the effect of lower neck lymph nodes and number of lymph nodes were also investigated in an exploratory training cohort to assess relevance within the ICON-S classification.Of 1907 patients with HPV+ oropharyngeal cancer, 661 (35%) were recruited at the training centre and 1246 (65%) were enrolled at the validation centres. 5-year overall survival was similar for 7th edition TNM stage I, II, III, and IVA (respectively; 88% [95% CI 74-100]; 82% [71-95]; 84% [79-89]; and 81% [79-83]; global p=0·25) but was lower for stage IVB (60% [53-68]; p0·0001). 5-year overall survival did not differ among N0 (80% [95% CI 73-87]), N1-N2a (87% [83-90]), and N2b (83% [80-86]) subsets, but was significantly lower for those with N3 disease (59% [51-69]; p0·0001). Stage classifications derived by RPA and AHR models were ranked according to survival performance, and AHR-New was ranked first, followed by AHR-Orig, RPA, and 7th edition TNM. AHR-New was selected as the proposed ICON-S stage classification. Because 5-year overall survival was similar for patients classed as T4a and T4b, T4 is no longer subdivided in the re-termed ICON-S T categories. Since 5-year overall survival was similar among N1, N2a, and N2b, we re-termed the 7th edition N categories as follows: ICON-S N0, no lymph nodes; ICON-S N1, ipsilateral lymph nodes; ICON-S N2, bilateral or contralateral lymph nodes; and ICON-S N3, lymph nodes larger than 6 cm. This resembles the N classification of nasopharyngeal carcinoma but without a lower neck lymph node variable. The proposed ICON-S classification is stage I (T1-T2N0-N1), stage II (T1-T2N2 or T3N0-N2), and stage III (T4 or N3). Metastatic disease (M1) is classified as ICON-S stage IV. In an exploratory training cohort (n=702), lower lymph node neck involvement had a significant effect on survival in ICON-S stage III but had no effect in ICON-S stage I and II and was not significant as an independent factor. Overall survival was similar for patients with fewer than five lymph nodes and those with five or more lymph nodes, within all ICON-S stages.Our proposed ICON-S staging system for HPV+ oropharyngeal cancer is suitable for the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer TNM classification. Future work is needed to ascertain whether T and N categories should be further refined and whether non-anatomical factors might augment the full classification.None.