Sinonasal squamous cell carcinoma in the United States: Temporal and geographic patterns associated with HPV testing and positivity.

OBJECTIVES: Human papillomavirus (HPV) has emerged as a potential etiological factor in sinonasal squamous cell carcinoma (SNSCC), but a clear understanding of HPV prevalence and its temporal patterns in SNSCC remains elusive. This study aimed to investigate temporal trends in HPV testing and positivity rates, and explore demographic and geographic factors associated with these trends. METHODS: A retrospective cohort study included patients diagnosed with invasive SNSCC between 2011 and 2017 from the US National Cancer Database (NCDB). Prevalence ratios (PR) of HPV positivity and testing rates were estimated with the corresponding 95% confidence interval (95% CI). RESULTS: The overall HPV testing rate was 45.4 % (N = 1762/3880), and the prevalence of HPV testing significantly decreased during the study period (adjusted PR: 0.97, 95 % CI: 0.95 - 0.99, p < 0.001). Overall HPV positivity frequency was 37.3 % (N = 650/1741), and the overall prevalence of HPV positive tumors significantly increased during the study period (adjusted PR: 1.04, 95 % CI: 1.02 - 1.05, p < 0.001). The increase in HPV positivity rate was observed solely in the white population (unadjusted PR: 1.10, 95 % CI: 1.06 - 1.14; p < 0.001). A significant geographical variation was observed for both HPV testing (range: 28.6 % - 61.7 %) and positivity (range: 28.3 % - 44.7 %). CONCLUSIONS: This study provides novel insights into the temporal trends and demographic factors associated with HPV testing and positivity in SNSCC. Despite increasing HPV positivity rates, disparities in testing rates persist, highlighting the need for standardized testing protocols and targeted interventions.

Prognostic Significance of Extranodal Extension in HPV-Mediated Oropharyngeal Carcinoma: A Systematic Review and Meta-analysis.

OBJECTIVE: To determine the prognostic role of extranodal extension (ENE) among patients with human papilloma virus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) through a systematic review and meta-analysis of institutional studies. DATA SOURCES: MEDLINE, Embase, Scopus, and PubMed. REVIEW METHODS: Two independent authors searched the databases on December 3, 2019, to identify studies of HPV+ OPSCC comparing prognostic outcomes stratified by ENE. The I2 statistic was used to determine study heterogeneity. Fixed and random effects models were used to determine hazard ratios (HRs) with 95% CIs. RESULTS: Eighteen observational studies met inclusion criteria, yielding 3603 patients with HPV+ OPSCC (1521 ENE+ and 2082 ENE-) with a median follow-up of 49 months. The presence of pathologic ENE (pENE) and radiologic ENE (rENE) was associated with decreased overall survival (pENE HR, 1.89 [95% CI, 1.15-3.13], I2 = 35%; rENE HR, 2.64 [95% CI, 1.46-4.78], I2 = 75%) and distant recurrence (pENE HR, 3.23 [95% CI, 1.25-8.33], I2 = 0%; rENE HR, 3.83 [95% CI, 1.88-7.80], I2 = 0%). Neither pENE nor rENE was associated with locoregional recurrence (pENE HR, 0.75 [95% CI, 0.20-2.84], I2 = 0%; rENE HR, 2.03 [95% CI, 0.86-4.79], I2 = 0%). pENE was not associated with disease-specific survival (pENE HR, 1.45 [95% CI, 0.84-2.49], I2 = 0%). CONCLUSION: pENE and rENE are moderately associated with an increased risk of all-cause mortality and recurrence with distant metastasis in a cohort of patients with HPV+ OPSCC. These findings may be used to inform exclusion criteria for deintensification trials and assist in refined risk stratification.

Diagnosis and Management of Squamous Cell Carcinoma of Unknown Primary in the Head and Neck: ASCO Guideline.

PURPOSE: To provide evidence-based recommendations to practicing physicians and other health care providers on the diagnosis and management of squamous cell carcinoma of unknown primary in the head and neck (SCCUP). METHODS: The American Society of Clinical Oncology convened an Expert Panel of medical oncology, surgery, radiation oncology, radiology, pathology, and advocacy experts to conduct a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 2008 through 2019. Outcomes of interest included survival, local and regional disease control, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS: The literature search identified 100 relevant studies to inform the evidence base for this guideline. Four main clinical questions were addressed, which included subquestions on preoperative evaluations, surgical diagnostic and therapeutic procedures, appropriate pathology techniques, and adjuvant therapy. RECOMMENDATIONS: Evidence-based recommendations were developed to address preoperative evaluation for patients with a neck mass, surgical diagnostic and therapeutic procedures, appropriate treatment options in unilateral versus bilateral SCCUP.Additional information is available at www.asco.org/head-neck-cancer-guidelines.

Predictors of swallow function after transoral surgery for locally advanced oropharyngeal cancer.

OBJECTIVE: Transoral surgery (TOS) for oropharyngeal carcinoma (OPC) is steadily becoming more routine. Expected posttreatment swallow function is a critical consideration for preoperative counseling. The objective of this study was to identify predictors of swallow dysfunction following TOS for advanced tumor (T)-stage (T3-T4) OPC. METHODS: A retrospective review from 1997 to 2016 at a single institution was performed. Eighty-two patients who underwent primary transoral resection of locally advanced OPCs with at least 1 year of postoperative follow-up were included. The primary outcome measure was swallow function, as measured by the Functional Outcomes Swallowing Scale (FOSS) at 1 year postoperatively. Operative reports were reviewed, and the extent of resection and type of reconstruction were documented. Conjunctive consolidation was then performed to incorporate multiple variables and their impact on swallow function into a clinically meaningful classification system. RESULTS: Fifty-six patients (68%) had acceptable swallowing at 1 year. T4 tumor stage and receipt of adjuvant chemoradiation therapy (CRT) were strongly associated with poor swallowing but did not reach statistical significance. Only base of tongue (BOT) resection ≥50% (odds ratio [OR] 3.19, 95% confidence interval [CI] 1.21-8.43) and older age (OR 1.06, 95% CI 1.00-1.12) were significantly associated. Utilizing T-stage, adjuvant CRT, and BOT resection, a conjunctive consolidation was performed to develop a classification system for swallow dysfunction at 1 year. CONCLUSION: This study provides risk stratification for swallow function at 1 year following primary transoral resection of locally advanced OPCs. BOT resection ≥50%, especially when coupled with T4 tumor stage or adjuvant CRT, was associated with poor long-term swallow outcomes. LEVEL OF EVIDENCE: 3 Laryngoscope, 130:94-100, 2020.

Eliminating Postoperative Radiation to the Pathologically Node-Negative Neck: Long-Term Results of a Prospective Phase II Study.

PURPOSE: The volume treated with postoperative radiation therapy (PORT) is a mediator of toxicity, and reduced volumes result in improved quality of life (QOL). In this phase II trial, treatment volumes were reduced by omitting PORT to the pathologically negative (PN0) neck in patients with primary head and neck squamous cell carcinoma. METHODS: Patients with head and neck squamous cell carcinoma who underwent surgical resection and neck dissection with a PN0 neck and high-risk features mandating PORT to the primary and/or involved neck were eligible. The primary end point was greater than 90% disease control in the unirradiated neck. QOL was evaluated using the MD Anderson Dysphagia Inventory and the University of Michigan patient-reported xerostomia questionnaire. RESULTS: Seventy-three patients were enrolled, and 72 were evaluable. Median age was 56 years (range, 31 to 81 years); 58 patients were male, and 47 (65%) had a smoking history. Sites included oral cavity (n = 14), oropharynx (n = 37), hypopharynx (n = 4), larynx (n = 16), and unknown primary tumor (n = 1). According to the American Joint Committee on Cancer Staging Manual (7th edition), 67 patients (93%) had stage III/IV disease, and 71% of tumors involved or crossed midline. No patient had contralateral neck PORT. In 17 patients (24%), only the primary site was treated. At a median follow-up of 53 months, two patients experienced treatment failure of the PN0 unirradiated neck; they also experienced treatment failure locally. Unirradiated neck control was 97% (95% CI, 93.4% to 100.0%). Five-year rates of local control, regional control, progression-free survival, and overall survival were 84%, 93%, 60%, and 64%, respectively. QOL measures were not significantly different from baseline at 12 and 24 months post-PORT (P > .05). CONCLUSION: Eliminating PORT to the PN0 neck resulted in excellent control rates in the unirradiated neck without long-term adverse effects on global QOL.

A Review of and Algorithmic Approach to Soft Palate Reconstruction.

IMPORTANCE: The soft palate contributes to deglutition, articulation, and respiration. Current reconstructive techniques focus on restoration of both form and function. The unique challenges of soft palate reconstruction include maintenance of complex upper aerodigestive tract function, with minimal local or donor site morbidity. OBJECTIVE: To review the literature on soft palate reconstruction and present an algorithm on how to approach soft palate defects based on this review. EVIDENCE REVIEW: A review of the literature for articles reporting studies on and that described concepts related to soft palate reconstruction was conducted in March 2017. In all, 1804 candidate titles and abstracts were independently reviewed. English-language articles that discussed acquired soft palate defect reconstruction were included. Non-English language studies without available translations, studies on primary soft palate defect reconstruction (ie, cleft palate repair) and primary cleft palate repair, studies in which the soft palate was not the focus of the article, and studies involving animals were excluded. FINDINGS: The following observations were made from the review of 92 included articles. Soft palate anatomy is a complex interplay of multiple structures working in a 3-dimensional area. Three of the authors created an initial algorithmic framework based on the selected studies. After this, a round table discussion among 3 authors considered experts was used to refine the algorithm based on their expert opinion. The 4 most important factors were determined to be defect size, defect extension to other subsites, defect thickness, and history of radiotherapy or planned radiotherapy. This algorithm includes both surgical and nonsurgical options. Defects in the soft palate not only affect the size and shape of the organ but, more critically, the function. The reconstructive ladder is used to help maximize the remaining soft palate functional tissue and minimize the effect of nonfunctional implanted tissue. Partial-thickness defects or defects less than one-fourth of the soft palate may not require locoregional tissue transfer. Patients with a history of radiotherapy or defects of up to 75% of the soft palate may require locoregional tissue transfer. Defects greater than 75% of the soft palate, defects that include exposure of the neck vasculature, or defects that include significant portions of the hard palate or adjacent oropharyngeal subsites may require free tissue transfer. Obturation should be considered a second-line option in most cases. CONCLUSIONS AND RELEVANCE: Ideal reconstruction of the soft palate relies on a comprehensive understanding of soft palate anatomy, a full consideration of the armamentarium of surgical techniques, consideration for adjacent subsite deficits, and a detailed knowledge of various intrinsic and extrinsic patient factors to optimize speech, swallowing, and airway outcomes. The included algorithm may serve as a useful starting point for the surgeon when considering reconstruction.

Long-term analysis of transorally resected p16 + Oropharynx cancer: Outcomes and prognostic factors.

OBJECTIVE: We observed high survival in a previous report of a p16-positive, oropharyngeal carcinoma (OPC) cohort treated primarily with transoral laser microsurgery (TLM) ± adjuvant therapy and followed for ≥ 12 months. To address long-term outcomes of primary transoral surgery for this unique disease, we present an updated analysis of our cohort with extended follow-up. METHODS: A prospectively assembled TLM cohort of 171 OPC patients was analyzed for disease-free, disease-specific, and overall survival (disease-free survival [DFS], disease-specific survival [DSS], overall survival [OS]) and functional outcomes, with a minimum follow-up of 60 months or to death. RESULTS: Median follow-up was 103 (60-201) months. Five-year DFS, DSS, and OS estimates were 85% (95% confidence interval [CI]: 80%-91%), 93% (95% CI: 89%-97%), and 90% (95% CI: 86%-95%). Recurrence occurred in 20 (12%; 7 locoregional, 13 distant); median time to recurrence was 18.8 months; and 90% occurred within 48 months. Age, smoking, American Joint Committee on Cancer 8th edition clinical tumor-category, pathologic tumor (pT)-category, pathologic tumor-node-metastasis (pTNM), and any adjuvant were significantly associated with disease-free survival in multivariable analyses, whereas pT-category, pN-category, TNM grouping, and angioinvasion were associated with DSS. A second primary developed in six (3.5%) patients. Indications for gastrostomy were recurrence/second primary (11), postadjuvant esophageal stenosis (6), comorbidities (3), and osteo/chondroradionecrosis (3); only seven (4%) had a gastrostomy tube in the absence of these factors, all of whom received adjuvant therapy. Two had a tracheostomy tube [chondoradionecrosis (1), recurrence (1)]. CONCLUSION: High 5-year survival and locoregional control were observed, with recurrence occurring more commonly as distant metastasis. The observed time to recurrence suggests posttreatment oncologic surveillance for at least 48 months. Identified prognosticators will inform adjuvant treatment considerations, trial planning, and patient counseling for long-term outcomes. Laryngoscope, 2018 LEVEL OF EVIDENCE: 2b Laryngoscope, 129:1141-1149, 2019.

Survival for HPV-positive oropharyngeal squamous cell carcinoma with surgical versus non-surgical treatment approach: A systematic review and meta-analysis.

The optimal management of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) with primary surgical versus non-surgical treatment is unclear. The objective of this systematic review was to evaluate the literature and compare survival for primary surgical versus non-surgical treatment of HPV-positive OPSCC. We performed a comprehensive literature search of multiple electronic databases for relevant articles up to February, 2017. Studies reporting mortality or hazard ratio (HR) for overall survival (OS) in primary HPV-positive OPSCC patients were eligible. Seventy-three articles were eligible, of which 66 included single-modality (19 surgical, 47 non-surgical), and 7 included both surgical and non-surgical modalities. There were no randomized studies comparing outcomes between both modalities. In a meta-analysis of both-modality studies, OS with surgical treatment was not significantly different from non-surgical treatment (pooled HR 1.12; 95% CI: 0.35, 3.57). There was significant heterogeneity between studies (I2 = 82.4%). Among single-modality studies, the mortality rate was lower with surgical [pooled proportion 0.15 (95% CI: 0.09, 0.21)] versus non-surgical treatment [0.20 (95% CI:0.15, 0.24)]. In a subgroup analysis, OS was higher for HPV-positive versus HPV-negative OPSCC, irrespective of the treatment modality. We conclude that there is an absence of high-quality studies that compare survival for HPV-positive OPSCC treated with primary surgical versus non-surgical approach. The available data suggest no statistical or clinically meaningful difference in survival between the two approaches. HPV-positivity was a key prognostic factor irrespective of treatment modality. Further high-quality studies with consistent data reporting are needed to inform the choice for optimal treatment modality for HPV-positive OPSCC.

Predictors of acute throat or esophageal patient reported pain during radiation therapy for head and neck cancer.

BACKGROUND AND PURPOSE: Acute pain during weekly radiotherapy (RT) to the head and neck is not well characterized. We studied dose-volume metrics and clinical variables that are plausibly associated with throat or esophageal pain as measured with a weekly questionnaire during RT. MATERIALS AND METHODS: We prospectively collected weekly patient-reported outcomes from 122 head and neck cancer patients during RT. The pain score for each question consisted of a four-level scale: none (0), mild (1), moderate (2), and severe (3). Univariate and multivariate ordinal logistic regression analyses were performed to investigate associations between both esophageal and throat pain and clinical as well as dosimetric variables. RESULTS: In multivariate analysis, age was significantly associated with both types of pain, leading to odds ratio (OR) = 0.95 (p = 0.008) and OR = 0.95 (p = 0.007) for esophageal and throat pain, respectively. For throat pain, sex (OR = 4.12; p = 0.010), with females at higher risk, and fractional organ at risk (OAR) mean dose (OR = 3.30; p = 0.014) were significantly associated with throat pain. CONCLUSIONS: A fractional OAR mean dose of 1.1 Gy seems a reasonable cutoff for separating no or mild pain from moderate to severe esophageal and throat pain. Younger patients who received RT experienced more esophageal and throat pain. Females experienced more throat pain, but not esophageal pain.

Oncologic outcomes of extended neck dissections in human papillomavirus-related oropharyngeal squamous cell carcinoma.

BACKGROUND: Oncologic outcomes of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (SCC) requiring resection of major muscular or neurovascular tissue during neck dissection for invasive nodal disease remain uncertain. METHODS: Patients with HPV-related oropharyngeal SCC requiring resection of major muscular or neurovascular tissue during their neck dissections were retrospectively identified. RESULTS: Seventy-two patients were included. Regional and distant recurrences occurred in 6% and 17% of patients. Advanced T classification, pathological node number of 5 or more, and omission of adjuvant therapy were associated with decreased disease-free survival (DFS). The addition of adjuvant chemotherapy was not associated with improved survival. CONCLUSION: Patients with invasive nodal disease from HPV-related oropharyngeal SCC can be managed with up-front surgery and adjuvant therapy, as indicated with good regional control. Although distant recurrence was the primary site of failure, adjuvant chemotherapy was not associated with improved outcomes. The T classification, node number, and adjuvant radiotherapy are independent prognostic factors in this patient population.

Comparison of unilateral versus bilateral intensity-modulated radiotherapy for surgically treated squamous cell carcinoma of the palatine tonsil.

BACKGROUND: The authors hypothesized that unilateral intensity-modulated radiotherapy (IMRT) would decrease toxicity compared with bilateral IMRT for patients with lateralized palatine tonsillar cancer and a neck classification of N0 to N2b, with similar oncological outcomes. METHODS: A total of 154 patients were treated with postoperative IMRT from 1997 through 2013. Data were collected prospectively from 2005 to 2013 and retrospectively collected before 2005. Of those patients with lateralized primary and N0 to N2b disease, 48 received unilateral IMRT (group 1) and 59 received bilateral IMRT (group 2); a total of 47 patients had nonlateralized primary or N2c to N3 disease and received bilateral IMRT (group 3). RESULTS: The median follow-up was 5.5 years. The 5-year locoregional control rates were similar in group 1, group 2, and group 3 (100%, 96%, and 94%, respectively; pooled comparison: P = .39 and group 1 vs group 2 comparison: P = .19). The 5-year overall survival rates were similar in group 1, group 2, and group 3 (85%, 79%, and 76%, respectively; pooled comparison: P = .60 and group 1 vs group 2 comparison: P = .25). There were no contralateral neck recurrences noted among unilaterally treated patients. Unilateral IMRT reduced acute toxicity and improved patient-reported quality of life compared with bilateral IMRT. CONCLUSIONS: Unilateral IMRT appears to reduce acute toxicity and achieves oncological outcomes similar to those of bilateral IMRT in selected patients with lateralized palatine tonsillar cancer with a neck classification of N0 to N2b. Cancer 2017;123:4594-4607. © 2017 American Cancer Society.

Transoral Resection of Human Papillomavirus (HPV)-Positive Squamous Cell Carcinoma of the Oropharynx: Outcomes with and Without Adjuvant Therapy.

BACKGROUND: With the rise of oropharyngeal squamous cell carcinoma associated with human papillomavirus (HPV), appropriate treatment strategies continue to be tailored toward minimizing treatment while preserving oncologic outcomes. This study aimed to compare the outcomes for those undergoing transoral resection with or without adjuvant therapy for HPV-related oropharyngeal carcinoma. METHODS: A case-match cohort analysis was performed at two institutions on patients with HPV-related oropharyngeal squamous cell carcinoma. All the subjects underwent transoral surgery and neck dissection. The patients treated with surgery alone were matched 1:1 to those treated with surgery and adjuvant therapy using two groups identified as confounders: T-stage (T1/2 or T3/4) and number of pathologically positive lymph nodes (≤4 or >4). RESULTS: The study identified 105 matched pairs, with a median follow-up period of 42 months (range 3.1-102.3 months). The patients were staged as T1/T2 (86%) or T3/4 (14%). Each group had five patients with more than four positive lymph nodes. Adjuvant therapy significantly improved disease-free survival (hazard ratio [HR] 0.067; 95% confidence interval [CI] 0.01-0.62) and was associated with a lower risk of local and regional recurrence (risk ratio [RR] 0.096; 95% CI 0.02-0.47). No difference in disease-specific survival (HR 0.22; 95% CI 0.02-2.57) or overall survival (HR 0.18; 95% CI 0.01-2.4) was observed with the addition of adjuvant therapy. The risk of the gastrostomy tube was higher for those receiving adjuvant therapy (RR 7.3; 95% CI 2.6-20.6). CONCLUSIONS: Transoral surgery is an effective approach for the treatment of HPV-related oropharyngeal carcinoma. The addition of adjuvant therapy appears to decrease the risk of recurrence and improve disease-free survival but may not significantly improve overall survival.

Mandibular Lytic Lesion in Familial Paraganglioma Syndrome Type I: A Clinical Conundrum.

OBJECTIVE: The entity of primary mandibular paraganglioma (PGL) is not well accepted within the head and neck. Mandibular PGLs hitherto reported in literature are malignant metastatic lesions, mostly from a pheochromocytoma. METHODS: We report a case of mandibular lytic lesion in a young female with multifocal PGLs but no family history of PGLs. We also performed a literature search to identify published cases of mandibular PGL. RESULTS: Lack of established criteria for malignancy in a PGL made diagnosis and treatment challenging. Testing was negative for a pheochromocytoma and positive for mutation of succinate dehydrogenase gene encoding subunit D (SDHD), thus rendering a diagnosis of familial PGL syndrome type I. Due to the absence of prior published reports of nonmalignant, primary mandibular PGL, patient was treated with surgery and postoperative radiotherapy. Our literature search revealed 4 published cases of mandibular PGL, all of which had an osteoblastic appearance and were malignant. CONCLUSIONS: Isolated mandibular PGL does not always indicate a malignant metastatic lesion. Genetic testing is recommended in patients with early onset of PGL and/or multifocality even without a positive family history. Surgical resection alone with surveillance can be offered for such isolated lesions in the presence of familial PGL syndrome type I.

Retrograde Parotidectomy and facial nerve outcomes: A case series of 44 patients.

PURPOSE: The most common surgical method to remove benign parotid tumors remains the prograde approach. We examined if a retrograde surgical technique offers better outcomes than historical prograde controls. MATERIALS AND METHODS: A retrospective chart review at Stanford Hospital was conducted to identify retrograde parotidectomies between February 2012 and October 2014 that were staffed by the senior author (DS) with resident involvement. Facial nerve (FN) outcomes and other post-surgical parameters were recorded. RESULTS: We identified 44 consecutive cases and found that 18.2% (n=8) of patients experienced temporary paresis and 2.3% (n=1) experienced minor (HB 2) permanent paresis limited to one branch. The average hospital length of stay was 0.64 days and complication rate was 6.8%. CONCLUSION: The retrograde technique has complication rates comparable to historical rates for the prograde technique and is amenable to minimally invasive outpatient superficial parotidectomy.

Biomarker and Tumor Responses of Oral Cavity Squamous Cell Carcinoma to Trametinib: A Phase II Neoadjuvant Window-of-Opportunity Clinical Trial.

Purpose: Ras/MEK/ERK pathway activation is common in oral cavity squamous cell carcinoma (OCSCC). We performed a neoadjuvant (preoperative) trial to determine the biomarker and tumor response of OCSCC to MEK inhibition with trametinib.Experimental Design: Patients with stage II-IV OCSCC received trametinib (2 mg/day, minimum 7 days) prior to surgery. Primary tumor specimens were obtained before and after trametinib to evaluate immunohistochemical staining for p-ERK1/2 and CD44, the primary endpoint. Secondary endpoints included changes in clinical tumor measurements and metabolic activity [maximum standardized uptake values (SUVmax) by F-18 fluorodeoxyglucose positron emission tomography/CT), and in tumor downstaging. Drug-related adverse events (AE) and surgical/wound complications were evaluated.Results: Of 20 enrolled patients, 17 (85%) completed the study. Three patients withdrew because of either trametinib-related (n = 2: nausea, duodenal perforation) or unrelated (n = 1: constipation) AEs. The most common AE was rash (9/20 patients, 45%). Seventeen patients underwent surgery. No unexpected surgical/wound complications occurred. Evaluable matched pre- and posttrametinib specimens were available in 15 (88%) of these patients. Reduction in p-ERK1/2 and CD44 expression occurred in 5 (33%) and 2 (13%) patients, respectively. Clinical tumor response by modified World Health Organization criteria was observed in 11 of 17 (65%) evaluable patients (median 46% decrease, range 14%-74%). Partial metabolic response (≥25% reduction in SUVmax) was observed in 6 of 13 (46%) evaluable patients (median 25% decrease, range 6%-52%). Clinical-to-pathologic tumor downstaging occurred in 9 of 17 (53%) evaluable patients.Conclusions: Trametinib resulted in significant reduction in Ras/MEK/ERK pathway activation and in clinical and metabolic tumor responses in patients with OCSCC. Clin Cancer Res; 23(9); 2186-94. ©2016 AACR.

The Hybrid Transoral-Pharyngotomy Approach to Oropharyngeal Carcinoma: Technique and Outcome.

BACKGROUND: The indications, techniques, and outcomes for a minimally invasive surgical approach in oropharyngeal squamous cell carcinoma (OPSCC) unsuitable for transoral resection are not well-described. METHODS: A retrospective case series was performed using a prospectively assembled database of transoral surgery-treated OPSCC patients who also underwent a "hybrid" approach of combined transoral and limited pharyngotomy for tumor resection. Disease and functional outcomes were evaluated. RESULTS: Twenty patients underwent complete tumor resection using the hybrid approach. Median follow-up was 48 months. No postoperative pharyngocutaneous fistula occurred. One patient (5%) had a local recurrence. Kaplan-Meier estimates for disease-specific survival at 2 and 5 years were 94.4% (95% CI, 84%-100%) and 87% (95% CI, 70%-100%). All but 1 patient (due to chemoradiotherapy-related chondroradionecrosis) were decannulated, and 2 required long-term gastrostomy. CONCLUSION: In the absence of a favorable transoral access, the "hybrid" approach of combined transoral and limited pharyngotomy can accomplish margin-negative primary tumor resection, with a high degree of disease control and functional recovery in selected OPSCC patients.

Acellular dermal graft pharyngeal repair augmentation after laryngectomy.

PURPOSE: Pharyngocutaneous fistula (PCF) after laryngectomy continues to be a serious complication, especially after radiation. Recruitment of non-radiated tissue into the surgical defect may decrease the risk of fistula. These techniques however have significant morbidity and increases operative time. We hypothesized that using acellular dermal graft to reinforce the pharyngeal closure could decrease the risk of fistula, without the added morbidity of a vascularized flap. METHODS: We performed a retrospective chart review of all patients that underwent a laryngectomy between 2005 and 2015 at an acedemic tertiary referral center. Patients who underwent primary pharyngeal closure with Alloderm® reinforcement without any other flap reconstruction were identified. Basic demographics, previous treatment, operative technique and fistula were extracted from the medical records. The primary outcome was PCF rate. The time to closure, margin status and disease recurrence was also evaluated. RESULTS: Among 16 patients with AlloDerm® augmentation, eight had primary laryngectomy and eight had salvage laryngectomy. A total of three in the salvage laryngectomy with prior history of radiation developed PCF. The fistula closed in all three cases with conservative treatment. There was no PCF in the primary laryngectomy group without prior history of radiation. CONCLUSION: The rate of PCF among the salvage laryngectomy group with previous radiation did not differ from historical data. AlloDerm® can however, provide a simple alternative for repair in radiation patients where flap cannot be performed for pharyngeal reconstruction. In non-radiated patients, AlloDerm® augmentation may have a protective effect on fistula formation.