Van Abel, Kathryn M

AbstractObjective The objective of this study is to describe the clinical presentation, tumor characteristics, natural history, and treatment patterns of sinonasal osteosarcoma.Methods Fourteen patients who had been treated for osteosarcoma of the nasal cavity and paranasal sinuses at a tertiary care center were reviewed. In addition, a systematic review of the literature for osteosarcoma of the sinonasal cavity was performed.Results In a systematic review, including 14 patients from the authors' institution, 53 total studies including 88 patients were assessed. Median follow-up was 18 months (interquartile range: 8–39 months). The most common presenting symptoms were facial mass or swelling (34%), and nasal obstruction (30%). The most common paranasal sinus involved by tumor was the maxillary sinus (64%), followed by the ethmoid sinuses (52%). The orbit (33%), dura (13%) and infratemporal fossa (10%) were the most common sites of local invasion. The majority of patients underwent surgery followed by adjuvant therapy (52.4%). Increasing age was associated with decreased overall survival rate (unit risk ratio [95% confidence interval (CI)] = 1.02 [1.003–1.043]; p = 0.0216) and T4 disease was associated with decreased disease-specific survival rate (hazard ratio [HR] = 2.87; p = 0.0495). The 2- and 5-year overall survival rates were 68 and 40%, respectively, while 2- and 5-year disease-specific survival rates were 71% and 44%, respectively.Conclusion Sinonasal osteosarcomas are uncommon tumors and can pose a significant therapeutic challenge. Increasing age and T4 disease are associated with worse prognosis. This disease usually warrants consultation by a multidisciplinary team and consideration of multimodality therapy.

Background: Anaplastic thyroid cancer (ATC) has poor prognosis with median overall survival (OS) of ∼6 months. We previously reported high PD-1/PDL-1 staining in ATC, raising the possibility of the productive application of the immunotherapeutic pembrolizumab. However, having found pembrolizumab to anecdotally have limited single-agent activity in ATC, we sought to alternatively define whether pembrolizumab might synergistically combine with chemoradiotherapy as initial ATC therapy. Methods: An investigator-initiated therapeutic phase 2 trial of pembrolizumab, 200 mg intravenously (IV) every 3 weeks, combined with chemoradiotherapy (docetaxel/doxorubicin, 20 mg/m 2 each IV weekly plus volumetric modulated arc therapy) was initiated as frontline therapy (with or without surgery) in ATC to assess efficacy and toxicities. Six-month OS was selected as the primary endpoint using a Simon's optimal design with interim analysis (targeting accrual of 25 patients; Cohort A: prior resection, Cohort B: no resection). Based on a prior patient cohort-treated similarly, but without pembrolizumab, the design was such that, if 6-month true survival is 75%, the probability of declaring the approach worthy of further pursuit would be 91%. Results: Three patients were enrolled, two with rapidly enlarging unresectable neck masses. Early tumor responses were favorable in all three, and all three satisfactorily completed: intended radiotherapy, preceding and radiotherapy-concurrent pembrolizumab, and concurrent chemoradiotherapy. However, all three patients died <6 months following therapy initiation—one from pulmonary metastases and two from otherwise unexpected fatal pulmonary complications occurring subsequent to chemoradiotherapy completion—prompting study closure. Conclusions: Although initially tolerated and effective in terms of locoregional disease control, disappointing survival outcomes compared with historical controls raise uncertainty that the piloted approach merits further pursuit in ATC.

AbstractBackgroundThe incidence of human papillomavirus (HPV)‐related oropharyngeal squamous cell carcinoma (OPSCC) is rising, even in elderly patients. The outcomes of transoral surgery (TOS) in this population are not entirely known.MethodsA retrospective review was performed at two institutions from October 2003 to September 2016 on patients 70 years or older with HPV‐related OPSCC treated with TOS.ResultsA total of 75 patients were included with a mean age of 74 years (70‐87 years). At a median follow‐up of 35.7 months, 3‐year overall survival was 81.5% and disease‐specific survival was 94.3%. Advanced cT stage (odds ratio, 2.74; 95% confidence interval, 1.13‐6.64) negatively impacted OS. Conjunctive consolidation was performed to create a staging system with patients older than 80 years, severe comorbidity, and cT3‐4 having worse survival.ConclusionsElderly patients with HPV‐related OPSCC treated with TOS have excellent survival and therefore should not be excluded from such therapy based on age alone.

PURPOSE The purpose of this study was to determine if dose de-escalation from 60 to 66 Gy to 30 to 36 Gy of adjuvant radiotherapy (RT) for selected patients with human papillomavirus–associated oropharyngeal squamous cell carcinoma could maintain historical rates for disease control while reducing toxicity and preserving swallow function and quality of life (QOL). PATIENTS AND METHODS MC1273 was a single-arm phase II trial testing an aggressive course of RT de-escalation after surgery. Eligibility criteria included patients with p16-positive oropharyngeal squamous cell carcinoma, smoking history of 10 pack-years or less, and negative margins. Cohort A (intermediate risk) received 30 Gy delivered in 1.5-Gy fractions twice per day over 2 weeks along with 15 mg/m 2 docetaxel once per week. Cohort B included patients with extranodal extension who received the same treatment plus a simultaneous integrated boost to nodal levels with extranodal extension to 36 Gy in 1.8-Gy fractions twice per day. The primary end point was locoregional tumor control at 2 years. Secondary end points included 2-year progression-free survival, overall survival, toxicity, swallow function, and patient-reported QOL. RESULTS Accrual was from September 2013 to June 2016 (N = 80; cohort A, n = 37; cohort B, n = 43). Median follow-up was 36 months, with a minimum follow-up of 25 months. The 2-year locoregional tumor control rate was 96.2%, with progression-free survival of 91.1% and overall survival of 98.7%. Rates of grade 3 or worse toxicity at pre-RT and 1 and 2 years post-RT were 2.5%, 0%, and 0%. Swallowing function improved slightly between pre-RT and 12 months post-RT, with one patient requiring temporary feeding tube placement. CONCLUSION Aggressive RT de-escalation resulted in locoregional tumor control rates comparable to historical controls, low toxicity, and little decrement in swallowing function or QOL.

Objectives/HypothesisSinonasal mucosal melanoma (SNMM) is a rare malignant neoplasm. No study to date has analyzed the impact that nodal metastases and distant metastases at diagnosis have on overall survival (OS) and disease‐specific survival (DSS).Study DesignRetrospective database review.MethodsThe Surveillance, Epidemiology, and End Results database was queried for cases of SNMM. Descriptive statistics were used analyze patient demographic and clinicopathologic variables. The Kaplan‐Meier model was used to analyze survival, and the Cox proportional hazards model was used for multivariate analysis.ResultsThree hundred twenty‐eight cases of SNMM were identified. The most frequent sinonasal anatomic location was the nasal cavity in 279 (73.0%) patients, followed by the maxillary sinus in 60 (15.7%) patients. Regional nodal metastases at diagnosis occurred in 33 (8.6%) patients, whereas distant metastases at diagnosis occurred in 41 (10.7%) patients. Five‐year OS was 22.7%, and 5‐year DSS was 26.8%. The presence of positive nodes at diagnosis (OS P < .0001, DSS P < .0001), distant metastases at diagnosis (OS P = .0442, DSS P = .0442), primary tumor site (OS P < .0001, DSS P < .0001), and increasing age (OS P = .0012, DSS P = .0016) were found to be significant as negative predictors of OS and DSS.ConclusionsSNMM is a rare pathologic entity with a poor prognosis. The presence of nodal and distant metastases at diagnosis are negative prognostic factors in OS and DSS. These factors can be used in the development of new models of risk stratification and to inform treatment strategies and surveillance patterns.Level of EvidenceNALaryngoscope, 130:622–627, 2020

Objectives Determine the effect of endoscopic skull base surgery (ESBS) on long‐term olfactory outcomes after surgery. Methods An English‐language search was conducted using the Cochrane, MEDLINE, Scopus, and Embase databases from January 2000 to October 2017 for adult patients undergoing ESBS with subjective and objective olfaction outcomes. Two authors independently examined articles to identify those meeting inclusion criteria. Studies examining objective olfactory outcomes after ESBS were included in the meta‐analysis. A random‐effects meta‐analysis of patients undergoing sellar and parasellar ESBS was conducted to compare preoperative and postoperative olfactory outcomes using the University of Pennsylvania Smell Identification Test (UPSIT) and Cross‐Cultural Smell Identification Test (CCSIT). Results Among 339 eligible articles, 29 articles met inclusion criteria. Twenty‐five of these focused on sellar and parasellar tumors. Individual articles not meeting criteria for meta‐analysis were qualitatively reported. Meta‐analysis showed there was no difference in preoperative and postoperative olfactory function after sellar and parasellar ESBS based on the UPSIT (five studies, mean difference [MD] = −1.03; 95% CI: −3.98, 1.93; P = .50) and the CCIST (three studies, MD = −0.77; 95% CI: −3.03, 1.49; P = .50). A pooled overall meta‐analysis revealed similar results (eight studies, effect size = −0.30; 95% CI: −0.79, 0.18; P = .22). However, heterogeneity for all meta‐analyses was high ( I 2 > 95%, P < .01), suggesting significant variation in the included studies. Conclusions Based on published objective olfaction outcomes after sellar and parasellar ESBS, there was no significant difference between preoperative and postoperative olfaction. Further prospective studies using validated objective measures of olfaction are required to improve our understanding on this subject. Level of Evidence 2a Laryngoscope , 129:1998–2007, 2019

AbstractBackgroundPrevious wide local excision prior to sentinel lymph node biopsy (SLNB) may have the potential to disrupt lymphatic channels, thus incorrectly identifying the sentinel node. The purpose of this study was to investigate: (1) regional recurrence rates of prior wide local excision compared to other biopsy techniques and (2) survival outcomes in patients with melanoma of the head and neck.MethodsBetween the years 2000 and 2016, 391 cases were reviewed with a median follow‐up time of 30 months in a large tertiary care center. Biopsy practices included shave, punch, wide local excision, and narrow margin excisional/Mohs, and associations with time to local or regional relapse and death from melanoma were evaluated. Main outcomes included identification of sentinel lymph nodes, overall survival, and melanoma‐specific survival.ResultsOf the 391 patients, biopsy patterns were as follows: 77 (19%) unknown biopsy, 30 (8%) prior wide local excision (WLE), 105 (27%) narrow margin excisional biopsy, 69 (18%) punch biopsy, and 110 (28%) shave biopsy. SLNB was successfully identified in all 30 patients whom had a prior WLE. There were 50 regional recurrences in the neck and 27 local recurrences with the median (IQR) at 1.2 years and 1.0 years, respectively. Multivariable associations of type of prior biopsy, depth of invasion, and nodal status with time to regional recurrence, local recurrence, overall survival, and melanoma‐specific survival were not significantly different.ConclusionsSentinel lymph node biopsy for melanoma of the head and neck can be successfully performed in patients after previous wide local excision.

BackgroundOlfactory nerve fibers are at risk of injury during transnasal endoscopic skull‐base approaches. Olfactory outcomes for various techniques have not been thoroughly investigated. This study aims to report long‐term olfactory outcomes when a cold knife upper septal limb incision technique is used compared to monopolar cautery.MethodsA prospective cohort study was performed at a tertiary referral center. Adult patients undergoing endoscopic approaches with septal incisions were randomized to cold knife or monopolar cautery groups. Patient demographics, clinical history, surgical data, and outcomes were collected. Preoperative, 3‐month, and 12‐month postoperative scores on the University of Pennsylvania Smell Inventory Test (UPSIT) and 22‐item Sino‐Nasal Outcome Test (SNOT‐22) were measured. Fisher's exact tests were performed for categorical variables and t tests were performed for continuous variables.ResultsTwenty‐two (22) patients (10 cold knife, 12 cautery) were enrolled between March 2016 and August 2017. The average age ± standard deviation was 50.2 ± 14.0 years (p = 0.59), 54% (p = 0.69) were female, and the primary pathology was pituitary adenoma (73%, p = 1.00). Preoperative, 3‐month, and 12‐month postoperative UPSIT scores were similar between the cold knife and cautery groups (32.8 vs 32.4, p = 0.80; 33.1 vs 33.0, p = 0.96; 33.6 vs 33.3, p = 0.84). On the “sense of smell/taste” question of the SNOT‐22, there was also no difference at all time points (p > 0.22).ConclusionThere was no significant change in patient UPSIT scores 1 year after transnasal skull‐base approaches, and no short‐term or long‐term differences between cold knife and cautery upper septal limb incision techniques. Our study supports an individualized approach based on surgeon preference.

AbstractBackgroundTreatment options of Ewing sarcoma of the head and neck include surgery, radiotherapy (RT), and chemoradiotherapy. However, local control can be challenging.MethodsWe conducted a retrospective review of all patients with head and neck Ewing sarcoma treated from 1972 to 2015 at a single tertiary care hospital.ResultsSeventeen patients met criteria (median 21 years, range 5‐58 years; 5 women). Mean follow‐up was 10.4 years (range 2.2‐39 years). Tumors occurred commonly in the cervical spine (5/17), the skull (3/17), and the paranasal sinuses (3/17). A total of 14 of 17 patients underwent surgical resection, 9 with gross total resection. After multimodality therapy, the 5‐year overall survival (OS) and recurrence‐free survival (RFS) was 87% and 75%, respectively.ConclusionCombined multimodal treatment resulted in a 5‐year OS and RFS of 87% and 75%, respectively. Aggressive surgical resection with adjuvant chemoradiotherapy should be considered. Although negative margin surgery is the goal, subtotal resection may be acceptable in the setting of adjuvant treatment.