Citations

6095 Background: Prognosis for patients (pts) with locally-advanced, HPV-positive oropharynx squamous cell carcinoma (HPV+OPSCC) is significantly better than for pts with HPV-negative head and neck squamous cell carcinoma (HNSCC). Historic survival of pts with metastatic HNSCC is 6-9 months with palliative therapy. However, the prognosis and survival of pts with HPV+OPSCC with distant metastases is not known. Methods: Pts with HPV+OPSCC with distant metastatic disease were identified from databases from the departments of surgery, radiation, and medical oncology. Demographic and clinical data was abstracted from the medical record. All pts had confirmed HPV/p16+ disease. Results: Fifteen pts with metastatic HPV+ OPSCC were identified. The median age was 57 years (range 42-78, 15 male). The median pack-year smoking was 0 (range 0-120). Primary site included 10 tonsil and 5 tongue base. At diagnosis, one pt had stage III and 14 had stage IV disease (IVA: 9, IVB: 2, IVC: 3). T- and N-stage included T1 (1), T2 (10), T3 (3), T4 (1) and N1 (1), N2a (1), N2b (9), N2c (3), N3 (1). Extracapsular extension was seen in 8 pts, absent in 2, and unknown in 5. Seven pts had lymph node (LN) involvement at level IV/V. Initial therapy for locally-advanced disease included surgery followed by adjuvant radiation (RT) in 1 pt and chemoRT in 8, and definitive chemoRT in 3 pts. Three pts were metastatic at initial diagnosis. Of 6 pts with an isolated metastatic site, 3 pts are alive > 2 years from diagnosis of metastasis (median 1.97 years, range 0.49-2.29). Palliative therapy included surgery (3), RT (9), platinum chemo +/- cetuximab (8), cetuximab alone (2) or with a taxane (2). The most common sites of metastasis included bone (6), lung (5), and LNs (5). The 1-year survival rate after diagnosis of metastatic disease was 92%. The median time to diagnosis of metastatic disease after definitive therapy was 0.47 years (95% CI 0.19-1.29); 75% of pts who developed metastatic disease did so within 1 year of definitive therapy. Of note, 2 of the 15 pts developed a secondary immune-mediated malignancy (melanoma and non-HIV associated Kaposi’s sarcoma). Conclusions: The survival of pts with metastatic HPV+OPSCC is significantly better than that of historic controls.

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.

Radioiodine ablation is a commonly utilized treatment for differentiated thyroid carcinoma. Uptake of radioiodine can be enhanced by pretreatment with thyroid hormone withdrawal or administration of recombinant human thyroid‐stimulating hormone (rhTSH). rhTSH is generally well‐tolerated with minimal adverse effects. However, in patients with extensive tumor burden in confined anatomic spaces, rapid enlargement of normal or neoplastic thyroid tissue secondary to rhTSH administration can result in significant compressive effects. In this report, we describe a case of rapid airway deterioration requiring intubation in a patient with involvement of the thyroid cartilage by papillary thyroid carcinoma.Laryngoscope, 122:0000–0000, 2019 Laryngoscope, 130:2725–2727, 2020

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.

Background: Mandibular tori are a rare cause of difficult direct visualization of the upper aerodigestive tract. In the setting of aerodigestive tract pathology necessitating direct visualization, removal of mandibular tori may be required to facilitate treatment. Methods: In the first case, large bilateral symmetric mandibular tori were removed to facilitate access to the anterior commissure and removal of a T1 glottic squamous cell carcinoma (SCC). In the second case, large bilateral mandibular tori were removed to access a markedly exophytic SCC in the right vallecula. Subsequently, the tumor was removed with robotic assistance with excellent exposure. Results: Both patients were free of recurrence at last follow-up. Conclusion: Mandibular tori are an uncommon cause of difficult direct laryngoscopy. In situations that require direct visualization of the anterior commissure or base of tongue for diagnosis and management of lesions, surgical removal of the tori may be required as in the cases presented here.

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.

6071 Background: Phase III data suggests a benefit of HDC in the adjuvant setting, but the effect of HDC and WC on long term survival and for HPV+ HNSCC is unknown. Methods: Data from a published retrospective study (Geiger Oral Onc 2013) of HDC vs WC in resected HNSCC was updated. Overall survival (OS) and recurrence-free survival (RFS) was assessed by Kaplan-Meier method for all pts and by HPV status. Multivariate analyses were performed to assess impact of HPV status, smoking, age, HDC vs WC, and cumulative cisplatin dose ( < 200mg/m2 vs ≥200 mg/m2). Results: 51 patients (pts) received HDC and 53 WC. Median follow-up was 8.7 yrs (0.8-13.7). For the whole cohort, HDC had significantly improved OS over WC (p = 0.0095; 5- and 10-yr OS 84% and 80% vs 72% and 60%). No OS benefit for HDC was seen in pts with HPV+HNSCC (5- and 10-yr OS 90% and 87% for HDC and 81% and 81% for WC; p = 0.51). For HPV-negative HNSCC, OS had borderline significance with HDC vs WC (5- and 10-yr OS 73% and 68% vs 65% and 44%; p = 0.06). For the whole cohort, there was no difference in 5- and 10-yr RFS (78% and 74% for HDC vs 72% and 62% for WC; p = 0.32). When analyzed by HPV status, there was no difference in RFS with HDC or WC for either HPV+ (p = 0.43) or HPV-negative HNSCC (p = 0.97). On multivariate analyses of OS for all pts, only HPV status was significant (p = 0.0011; HR 0.27, CI 0.12-0.62). For HPV+ HNSCC, there was no significant predictor of OS. For non-HPV HNSCC, the benefit of HDC approached significance with a decreased risk of death (HR 0.38; p = 0.07). For all pts, those who received ≥200mg/m2 had significantly improved OS (5-yr 90% vs 72% and 10-yr 86% vs 61%; p = 0.004). By HPV status, cumulative dose had no significant effect on OS. Conclusions: OS is better with HDC and with cumulative dose > 200 mg/m2 in unselected patients. The benefit of cisplatin is likely higher for non-HPV HNSCC. A difference in OS with no difference in RFS suggests non cancer-related causes of death in the WC cohort. Ability to receive HDC could be a surrogate marker of comorbidity. [Table: see text]