Background: New therapies have changed melanoma treatment after 2011; however, these changes have not been studied well, especially in BRAFMut melanomas. Methods: We studied 4197 melanoma patients who received systemic therapy in 2011-17 in the US electronic medical record database OSCER. Among these, 1687 (40%) were studied for treatments by line of therapy (LOT) and biomarkers from 2011-16. Results: Therapies included: 64% checkpoint inhibitors (CPI), 19% BRAF/MEK inhibitors (BRAF/MEKi), 17% chemotherapy, 16% cytokines, and 1% oncolytic viral therapy. In 2011-17, overall CPI use increased from 23% to 81% (pembrolizumab 32%, nivolumab 23%, ipilimumab/nivolumab 21%) but ipilimumab use decreased to 13%. BRAF/MEKi use did not change (20-21%) but vemurafenib (2% in 2017) was replaced by dabrafenib/trametinib and cobimetinib/vemurafenib (14% and 4%). Cytokine and chemotherapy use declined (43% to 3% and 35% to 7%, respectively). During 2011-17, CPI and BRAF/MEKi were used more in LOT 1-4 (60% and 25%) than as adjuvant (30% and 2%), whereas cytokines were used as adjuvant only (64%). CPI were used most in NRASMut (85%) and less in BRAFMut, BRAFwt, or NRASwt (57-66%). In BRAFMut, CPI use was higher in stage III (62%) than IV (52%) unlike in BRAFwt (52% stage III vs. 90% stage IV). BRAFi were used in 65% of BRAFMut, more in stage IV than III (79% vs. 34%). BRAFMut and NRASMut received less adjuvant therapy than wild-type (20-22% vs. 28-31%) but more LOT (BRAFMut had 89% LOT 1, 37% LOT 2, 13% LOT 3, 5% LOT 4+). The table compares treatment changes in BRAFMut melanoma between 2011-14 and 2015-16.Table: 1280PTreatment changes in BRAFmut melanoma between 2011-14 and 2015-16Therapy2011-142015-16AdjuvantLOT 1LOT 2AdjuvantLOT 1LOT 2BRAF/MEKiVemurafenib12%28%12%05%5%Dabrafenib/Trametinib4%21%26%9%43%38%Cobimetinib/Vemurafenib0<1%2%04%10%Dabrafenib04%8%04%2%Trametinib02%4%01%2%CPIIpilimumab14%23%20%35%8%5%Pembrolizumab1%7%11%7%13%21%Nivolumab07%12%9%10%21%Ipilimumab/Nivolumab1%6%7%7%15%12%Cytokines60%7%1%33%3%0Chemotherapy2%4%7%03%0 Open table in a new tab Conclusions: Checkpoint inhibitors have replaced other advanced melanoma therapies, providing more treatment options to patients with BRAFMut melanoma. Legal entity responsible for the study: Amgen Inc. Funding: Amgen Inc. Disclosure: L. Raskin: Employee, Stock ownership: Amgen Inc. S. Shah, J. Buchanan, D. Cohan: Employee, Stockholder: Amgen Inc. All other authors have declared no conflicts of interest.

Objectives/HypothesisTo evaluate subsite-specific differences in survival between squamous cell carcinomas of the base of tongue and tonsillar fossa in a modern cohort likely to have been treated with intensity-modulated radiation therapy, chemotherapy for stage III and IV, and have had a high incidence of human papillomavirus-associated tumors.Study DesignRetrospective cohort analysis utilizing data from the Surveillance, Epidemiology, and End Results program of patients with base of tongue and tonsillar fossa squamous cell carcinoma from 2004 to 2011.MethodsThe cohort included 15,299 primary base of tongue and tonsillar fossa squamous cell carcinoma patients without distant metastases treated between 2004 and 2011. Subsite differences in overall survival and disease-specific survival were examined with Kaplan-Meier curves. Multivariate cox proportional hazard ratios were estimated for overall and disease-specific survival.ResultsThe cohort included 7,220 (47.2%) base of tongue and 8,079 (52.8%) tonsillar fossa squamous cell carcinoma patients. Overall survival with all stages combined favored tonsillar fossa (P < .001) and remained superior when stratified by stage. In multivariate analyses adjusted for age, gender, race, and treatment, the hazard ratio for overall survival was superior for tonsillar fossa tumors compared to base of tongue tumors for all stages (stage 1, P = .041; stage 2, P = .006; stages 3 and 4, P < .001). Disease-specific survival also favored improved outcomes for tonsillar fossa.ConclusionsIn this large modern cohort, overall and disease-specific survival favored outcomes in tonsillar fossa compared with base of tongue. Further study is required to evaluate factors that influence survival differences between tonsillar fossa and base of tongue despite modern therapy.Level of Evidence4 Laryngoscope, 127:1087-1092, 2017

Objective The study evaluated the addition of surgery (S) to radiation (RT) on survival of squamous cell carcinomas (SCC) of tonsillar-fossa (TF) in a modern cohort with similar epidemiology and treatment as current patients. Study Design Retrospective analysis utilizing Surveillance, Epidemiology, and End Results (SEER) Program data. Results For all stages combined TF patients who received S+RT had superior OS (p < 0.01) and DSS (p < 0.01). For each stage OS and DSS was superior for S+RT (p < 0.05). In multivariate analysis, HRs for OS were statistically significantly higher for TF patients (stage 2, 3, and 4) receiving RT alone (p < 0.001). Materials and Methods TF SCC patients treated with either S+RT or RT alone between 2004 and 2011 were examined (n = 6,476). Primary outcome measures included overall survival (OS) and disease specific survival (DSS). Cox proportional hazard ratios (HR) were estimated for patients treated with S+RT compared to RT alone. Conclusions OS and DSS were superior for all stages combined and for stages 2, 3, and 4 in TF patients who received S+RT compared to RT alone.

Treatment for head and neck cancer involves a combination of therapies that are highly toxic impacting both quality of life (QOL) and overall recovery period. The purpose of this project is to prospectively monitor QOL in a cohort of head and neck cancer patients while integrating QOL findings into patient care. QOL is currently being tracked in a head and neck radiation medicine clinic using the European Organization for Research and Treatment of Cancer (EORTC) Quality of life (QLQ)-30 and EORTC head and neck module (H&N)-35 questionnaires which was translated into a digital platform using a Research Electronic Data Capture (REDCap) survey format. Patients complete the survey at the beginning of treatment, end of treatment, and at each follow-up appointment (3 months, 6 months, 1 year). The REDCap survey program build enables automatic computation of scores upon patient completion. Results are therefore available for immediate review by the clinician. A total of 561 QOL surveys have been completed by 200 patients to date. Patients have completed surveys up to a period of 20 months following treatment.Abstract 211; Table 1Date8/19/1310/14/13*11/13/131/29/144/23/14**7/22/1410/15/144/15/15Global Health Status (QOL)5041.6616.6610083.3366.6691.6650Physical Functioning93.3393.3373.3310010073.3393.3386.66Emotional Functioning66.66752510066.665091.6650Cognitive Functioning10050501001005010066.66*Parkinson disease diagnosis suspected and referral made. **Parkinson disease medication adjustment needed and referral made. Open table in a new tab *Parkinson disease diagnosis suspected and referral made. **Parkinson disease medication adjustment needed and referral made. In this example the physician was able to diagnose a worsening of the patient’s Parkinson disease based on the results of the QOL, physical functioning, emotional functioning, and cognitive functioning scores. The physician was then able to refer her for immediate and appropriate therapy. Prospectively tracking QOL before, during, and after treatment provides clinicians with a more comprehensive understanding of factors related to changes in their patients’ QOL scores, allowing them to provide immediate treatment or appropriate referrals. Using a digital platform (REDCap Surveys) is a novel method for tracking and managing QOL factors in real time in a head and neck cancer population.

There is increasing interest in the use of robotic surgery in carcinoma of the oropharynx. The purpose of this study was to examine survival outcomes among 2 oropharyngeal subsites (tonsillar-fossa [TF] and base of tongue [BOT]). We conducted a retrospective cohort analysis utilizing data from the Surveillance, Epidemiology, and End Results (SEER) Program. The SEER cohort included 8073 primary BOT and TF SCC patients without distant metastases treated between 2004 and 2011. Primary outcome measures were subsite-based differences in overall survival (OS) and disease-specific survival (DSS) for TF and BOT patients stratified by overall stage and comparing treatment method for each subsite. Cox proportional hazard ratios were estimated for each group. For all stages combined, both BOT and TF patients who received surgery with radiation had superior OS (P<.01). The same was true when analyses were stratified by stage within each subsite. Multivariate hazard ratios adjusted for age, gender, race, and tumor grade for OS were statistically significantly higher for both BOT and TF patients who did not receive surgery compared to those who did receive surgery for each stage. In this SEER cohort, OS was superior in both BOT and TF patients who received surgery with adjuvant radiation. OPSCC survival may be improved by treating more BOT and TF patients with surgery and adjuvant radiation. As modern, less invasive surgical techniques such as transoral robotic surgery gain wider acceptance, approaches that combine surgery and radiation (with or without chemotherapy) while minimizing morbidity and lack of function should be attempted.

OBJECTIVES/HYPOTHESIS:The effect of smoking and human papillomavirus (HPV) on overall survival (OS) of oropharyngeal squamous cell carcinoma (OPSCC) patients undergoing concurrent chemotherapy (CCRT) remains unclear. STUDY DESIGN:Retrospective review. METHODS:Clinical characteristics of OPSCC patients treated between 2008 and 2015 with CCRT were abstracted from medical records. OS curves and multivariate cox proportional hazard ratios (HRs) were examined. RESULTS:Of 120 evaluable patients, 71% had HPV+ tumors. Median follow-up duration for the entire cohort was 41.5 months (range = 6-88 months). HPV+ current smokers experienced significantly worse 5-year OS (73% alive vs. 36% alive, P = .01) and there was a similar trend in HPV- current smokers (66% alive vs. 31% alive, P = .28) compared to former/never smokers undergoing CCRT. In a multivariate cox proportional hazard model adjusted for age, gender, and overall tumor stage, HPV+ current smokers experienced nearly a fourfold increase in overall mortality in comparison to HPV+ never/former smokers (HR = 3.68, 95% CI = 1.35-10.0). Similarly, current smokers with HPV- tumors (HR = 6.80, 95% CI = 1.11-41.67) had increased mortality compared to never/former smokers. CONCLUSIONS:Current smoking is associated with poor prognosis, independent of HPV status, in CCRT-treated OPSCC patients. Current smoking produced an approximately four- to sevenfold increase in risk of mortality for HPV+ and HPV- patients, respectively. Regardless of pack years and HPV status, efforts should be made to achieve smoking cessation before CCRT. LEVEL OF EVIDENCE:4. Laryngoscope, 126:2733-2738, 2016.

The effect of smoking and human papillomavirus (HPV) status on the survival of oropharyngeal squamous cell carcinoma (OPSCC) undergoing definitive concurrent chemoradiation (CCRT) remains unclear. The purpose of this review was to examine these effects on survival outcomes among a single institute population. This retrospective review of OPSCC patients treated with CCRT between 2008 and 2015 was conducted. All tumors were examined for HPV 16/18 status (+/). Smoking status and other clinical characteristics were abstracted from the electronic medical record. Former smokers are patients who quit within a month of diagnosis or treatment. Descriptive summaries, overall survival (OS), and multivariate cox proportional hazard ratios (HR) were completed. Out of 134 patients, 94 patients (71%) had HPV-positive (HPV+) tumors. Age, gender, and overall stage were not statistically different between patients with HPV+ or HPV-negative (HPV-) tumors. HPV+ patients had higher tumor grade (P<.01). Patients with HPV+ tumors had a higher percentage of never smokers than patients with HPV- tumors (10.3% vs 26.6%). Median pack-years were 18 for the HPV+ group versus 30 for the HPV- group. OS did not differ for HPV+ versus HPV- patients. Within HPV+ patients, current and former smokers had significantly worse OS than never smokers (P<.01). The same was true for HPV- patients, but the log-rank test for this group did not reach statistical significance (P=.06). The 3-year survival rate for former smokers in each group was similar (HPV+: 0.77 (0.60, 0.88) and HPV-: 0.75 (0.52, 0.88). Hazard ratios for OS among current smokers compared to never/former smokers in each patient group were statistically significantly higher. Current smoking is associated with poor prognosis, independent of HPV status in OPSCC patients treated with CCRT. Former smokers have similar outcomes irrespective of HPV tumor status. The amount of tobacco a patient is exposed to before diagnosis cannot be altered, but every effort should be made to get patients to quit smoking as soon as possible before CCRT regardless of HPV status.

Previous studies on treatment outcomes of patients with advanced oropharyngeal squamous cell carcinomas (OPSCC) have rarely analyzed subsite differences in detail in the era of human papillomavirus (HPV). The purpose of this study was to evaluate subsite-specific differences in survival between squamous cell carcinomas (SCC) of the base of tongue (BOT) and the tonsillar fossa (TF) in a cohort likely to have a high incidence of HPV-associated tumors. Retrospective cohort analysis utilizing data from the Surveillance, Epidemiology, and End Results (SEER) Program. The SEER cohort included 8073 primary BOT and TF SCC patients without distant metastases treated between 2004 and 2011. Primary outcome measures were subsite-based differences in overall survival (OS) and disease-specific survival (DSS). Cox proportional hazard ratios were estimated. Among the 8073 primary BOT and TF SCC patients, 3705 (46%) were BOT and 4368 (54%) were TF. Median age for BOT and TF patients was 62 and 58 years, respectively. Other clinical characteristics were similar between groups, but more TF patients had poorly differentiated tumors. Overall survival with all stages combined favored TF (P<.01) and remained superior when stratified by stage. In multivariate analyses adjusted for age, gender, race, and treatment, the hazard ratio (HR) for OS was superior for TF tumors in comparison to BOT tumors across all disease stages (stage I HR 1.28, 95% confidence interval [CI] 1.01-1.64; stage II HR 1.30, 95% CI 1.08-1.59; stage III HR 1.30, 95% CI 1.14-1.49; stage IV HR 1.14, 95% CI 1.00-1.30). Similar advantages were noted for DSS favoring improved outcomes for TF. In this large, modern cohort, OS and DSS favored outcomes in TF as compared with BOT. Further study is required to evaluate factors that influence subsite-based survival differences in TF and BOT patients in the era of HPV.

Subjects and Methods A total of 79 patients who underwent surgery for carotid artery dissection and/or resection were retrospectively analyzed in this study. Thirty-two patients (40.5%) received surgery as initial treatment, and 47 patients (59.5%) had surgical treatment for recurrences. Forty-four patients (55.7%) were treated with surgery alone, while surgical treatment was followed by postoperative radiotherapy in 15 patients (19%) and chemoradiation in 20 patients (25.3%). Intraoperative dissection and preservation of the carotid artery was achieved in 69 patients (87.3%). Ten patients underwent carotid resection with/ without reconstruction (12.7%). The carotid resections were reconstructed using the greater saphenous vein (n=7) or Expanded Polytetrafluoroethylene (ePTFE, n=2).

ASSOCIATED WITH HUMAN PAPILLOMA VIRUS (HPV) POSITIVE SQUAMOUS CELL CARCINOMA OF THE OROPHARYNX Vijayvel Jayaprakash, MBBS, PhD, Mihai Merzianu, MD, David M Cohan, MD, Sathiya P Marinuthu, MBBS, Ryan A Rimmer, MD, Hassan Arshad, MD, Mukund Seshadri, DDS, PhD, Moni A Kuriakose, MD, Wesley L Hicks Jr., MD, Graham W Warren, MD, PhD, Anurag K Singh, MD; Roswell Park Cancer Institute, Medical University of South Carolina

OBJECTIVE:Single-modality treatment, either with organ preservation surgery (OPS) or definitive radiation (RT), is the treatment of choice for patients with early supraglottic squamous cell carcinoma (SGC). However, studies comparing the effectiveness of these 2 techniques are lacking. This study compares the survival outcomes in early SGC patients treated with OPS versus RT.STUDY DESIGN:Secondary data analysis.SETTING:Surveillance, Epidemiology and End Results database.SUBJECTS AND METHODS:This study included adult patients with early-stage (T1N0, T2N0) SGC undergoing single-modality treatment with either OPS (with or without neck dissection [ND]) or RT between 1988 and 2008. Survival analysis was used to compare the overall survival (OS) and disease-specific survival (DSS) between patients treated with OPS+ND, OPS alone, and RT.RESULTS:A total of 2631 T1/T2 N0 SGC patients were identified, of whom 167 (6%) were treated with OPS+ND, 186 (7%) with OPS only, and 2278 patients (87%) with definitive RT only. In stage I (T1N0) SGC patients, a significantly better 5-year DSS was noted for both OPS+ND (81% vs 68%, hazard ratio [HR] = 0.61, P = .03) and OPS only (82% vs 68%, HR = 0.70, P = .05) when compared with definitive RT. For stage II (T2N0) patients, only OPS+ND resulted in a significantly better 5-year DSS (86% vs 60%, HR = 0.31, P < .001) when compared with patients treated with RT.CONCLUSIONS:Patients with early SGC who underwent OPS+ND had better OS and DSS than patients undergoing RT alone. OPS+ND may be considered a viable and preferred treatment option in these patients.

In Head and Neck Squamous Cell Carcinoma, nodal metastasis generally has a negative impact on prognosis. Human Papilloma Virus (HPV)-associated oropharyngeal SCC (OPSCC) has been shown repeatedly to confer better prognoses than HPV-negative oropharyngeal SCC, despite a high frequency of nodal metastases. We hypothesized that nodal metastasis has a reduced impact on survival in HPVpositive OPSCC than it does in HPV-negative OPSCC.

The survival rates and prognostic factors for salivary duct carcinoma (SDC) are not clear.

IMPORTANCE:Neck dissection is the standard staging procedure to ascertain the pathologic status of cervical lymph nodes in patients with oral cavity squamous cell carcinoma (OSCC), but it results in multiple morbidities.OBJECTIVE:To examine outcomes of patients with OSCC who underwent sentinel node biopsy (SNB) as the sole neck staging procedure.DESIGN:Retrospective review of patients who underwent SNB during the period 2005 through 2011.SETTING:National Cancer Institute–designated comprehensive cancer center.PARTICIPANTS:Thirty-eight patients with clinically T1 or T2N0 OSCC.INTERVENTIONS:Preoperative lymphoscintigraphy with intraoperative gamma probe localization was used. Sentinel lymph nodes were serially sectioned, formalin fixed, and examined at 3 levels. All patients with positive SNB results underwent neck dissection, and the patients with negative SNB results were observed clinically.MAIN OUTCOMES AND MEASURES:Sensitivity and predictive value of SNB, recurrence rates, and disease-specific survival rates.RESULTS:There were 18 T1 and 20 T2 tumors. Five patients had positive SNB results, of whom 3 had additional positive nodes on subsequent neck dissection. Two of 33 patients with negative SNB results developed a regional recurrence. The sensitivity and negative predictive value for staging the neck with SNB alone were 71% (5 of 7) and 94% (31 of 33), respectively. Mean follow-up was 31 months. The mean disease-free survival duration for patients with positive and negative SNB results was 30 and 65 months, respectively (P = .08). The disease-specific survival rate for patients with positive and negative SNB results was 80% and 91%, respectively. There was no significant difference in disease-specific survival between patients with true-negative and false-negative SNB results (34 vs 44 months; P = .38).CONCLUSIONS AND RELEVANCE:The majority of patients with positive results on SNB had additional positive nodes on neck dissection. A low rate of isolated neck recurrence was found in patients with negative results on SNB. Individuals with negative results on SNB exhibited better overall and disease-specific survival than those with positive results.

The purpose was to examine the effect of pretreatment weight status on loco-regional progression for patients with squamous cell carcinoma of the head and neck (SCCHN) after receiving definitive concurrent chemoradiation therapy (CCRT).In an expanded cohort of 140 patients, we retrospectively reviewed weight status and loco-regional progression of SCCHN patients treated with CCRT between 2004 and 2010.Pretreatment ideal body weight percentage (IBW%) was statistically significantly different for patients with disease progression than for those without progression (p = 0.02) but was not an independent predictor of progression. Median pretreatment IBW% was 118 (72-193) for the progression-free group and was 101.5 (73-163) for the group with progression. Both groups suffered clinically severe weight loss of approximately 9 % from baseline to end treatment.Pretreatment weight status, a very crude indicator of nutrition status, may have prognostic value in patients with SCCHN undergoing definitive CCRT. Inadequate nutritional status in these patients has been associated with poor clinical outcomes and decreased quality of life. Based on this report and others, the best next steps include routine validated malnutrition screening and the testing of evidence-based nutrition care protocols with the goals of minimizing weight loss and improvement of quality of life.

The palate is a critical structure, playing pivotal roles in speech, swallowing, and mastication. Reconstruction of the palate is among the most difficult challenges faced by head and neck reconstructive surgeons. The primary aims of this review are to catalog the evolution of the classification systems for palatal defects, discuss decision making surrounding the various options for hard palate reconstruction, and address the special challenges and techniques involved in soft palate reconstruction.The Okay Classification System has become the standard by which most hard palatal defects are assessed. Free tissue transfer seems to be becoming an increasingly important therapeutic modality for many hard and soft palate defects.Success in the management of palatal defects depends on accurate appreciation of the size and functional extent of each defect, careful patient selection, and specific attention to each patient's goals.

The palate is a critical structure, playing pivotal roles in speech, swallowing, and mastication. Reconstruction of the palate is among the most difficult challenges faced by head and neck reconstructive surgeons. The primary aims of this review are to catalog the evolution of the classification systems for palatal defects, discuss decision making surrounding the various options for hard palate reconstruction, and address the special challenges and techniques involved in soft palate reconstruction.The Okay Classification System has become the standard by which most hard palatal defects are assessed. Free tissue transfer seems to be becoming an increasingly important therapeutic modality for many hard and soft palate defects.Success in the management of palatal defects depends on accurate appreciation of the size and functional extent of each defect, careful patient selection, and specific attention to each patient's goals.

Biodegradable polymers are of interest for developing controlled protein drug delivery platforms. In this study, two poly (alpha-hydroxy) esters were formulated with Aerosol-OT, a surfactant stabilizer, to encapsulate the protein keratinocyte growth factor (KGF) for controlled release KGF is involved in a number of crucial biologic processes, most notably epithelial growth and repair. The concentration of KGF that caused a biological response in vitro was determined (optimally 10 ng/mL) and compared with the release of KGF from the two biodegradable polymer membrane formulations. Each polymer formulation released biologically relevant levels, 10 ng/mL of active KGF, although with different times release kinetics. The membrane composed of PLGA/AOT/KGF exhibited a faster release rate of KGF into solution after 120 h of degradation time than the release rate of the PLLA/AOT/KGF matrices. Cell seeding assays showed that both polymer matrices, when formulated with AOT, sustained cell growth. Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS) was used to characterize the distribution of AOT and KGF through the polymer membrane. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

Purpose of reviewThe goals of this article are: to briefly review oropharyngeal anatomy; to provide a review of the epidemiology of oropharyngeal cancer in the Western Hemisphere; to review the literature on the association of human papilloma virus with oropharyngeal cancer; to review the recent literature on evolving diagnostic techniques for oropharyngeal cancer; and to summarize accepted management strategies for oropharyngeal cancer by subsite.Recent findingsThe incidence of oropharyngeal cancer may be increasing among younger age groups in the Western Hemisphere, and this may be related to an increased association with human papillomavirus 16. The implications of this viral association with regard to outcomes and management strategies remain under investigation. Screening with toluidine blue, autofluorescence, or both may be useful adjuncts to physical examination and panendoscopy in assessing potentially invasive or dysplastic lesions of the oropharynx. These techniques remain under study. MRI and PET scan are proving to be useful techniques for assessing local extension, regional metastases, and recurrences of squamous cell carcinoma (SCC) of the oropharynx in selected cases. However, serial computed tomography scanning remains the imaging modality of choice in the United States. Early SCCs of the oropharynx (T1-2), in general, may be managed effectively with either surgery or primary irradiation, though, with either technique, clinicians must have a management plan for the neck. Advanced SCCs of the oropharynx (T3-4, nodally aggressive, or both) require multimodal approaches consisting of either surgery along with adjuvant irradiation or concurrent chemoradiation along with salvage surgery (as necessary).SummaryManagement of SCC of the oropharynx is in a period of transition because of evolving changes in our understanding of the oncogenic process; evolving diagnostic techniques; and evolving combinations of therapies, both surgical and nonsurgical. For the time being, we propose using local subsite and disease stage to guide therapeutic decision-making.