2017 Section 7 Green Book

S URGICAL MANAGEMENT OF OROPHARYNGEAL SCC

tion (ie, mandibulectomy with pharyngectomy and/or base of tongue removal). For analysis purposes, this was con- densed into groups of transoral (a or b) and open (c, d, or e) surgical approaches. All patients underwent neck dis- sections at the time of their primary resections, according to therapeutic guidelines. 33 Most patients were treated with adjuvant radiotherapy or adjuvant chemoradiotherapy based on standard National Comprehensive Cancer Net- work guidelines, which notably changed over time. After the publication by Bernier et al, 34 most high-risk patients were treated with postoperative concurrent chemoradio- therapy, whereas patients before 2004 were treated with radiation alone. Multiple studies have shown gastrostomy tube depend- ence to be a major negative predictor of quality of life in the head and neck cancer population. 35–37 In this study, gastrostomy tube presence was assessed and defined as the presence of a gastrostomy tube that was used for at least a portion of the diet. Gastrostomy tube presence was assessed at 0, 6, and 12 months postsurgery, and at last follow-up visit. A high density tissue microarray was created with rep- resentative samples from patients in the study. 38 Tumor p16 expression was evaluated by means of immunohisto- chemical staining using a mouse monoclonal antibody (MTM Laboratories CINTEC, Westborough, MA) and visualized with a Ventana XT autostainer (Ventana Medi- cal Systems, Tucson, AZ). Positive p16 expression was defined as diffuse nuclear and cytoplasmic staining in 50% or more of the tumor cells. All samples were further evaluated for HPV positivity via in situ hybridization for HPV16 (GenPoint HPV DNA Probe) or for high-risk HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 66 (INFORM HPV III Family 16 Probe (B); Ventana Medical Systems). Any definitive nuclear staining in the tumor cells was considered positive. Low-, intermediate-, and high-risk patients were defined as in the article by Ang et al. 15 Statistical methods Overall survival was defined as the time from the date of surgery to the date of death, with patients alive at the date of the last observation censored. Cox proportional hazards models were used to assess univariate associa- tions of biomarkers as predictors for death. Unadjusted hazard ratios (HRs) and 95% confidence intervals (CIs) are reported. Predictors of both clinical and statistical sig- nificance were evaluated in multivariable models for the entire cohort and within the HPV-negative and HPV- positive subgroups. These predictors included: surgical approach (transoral vs open), HPV status (positive vs neg- ative), extranodal extension (no vs yes), mucosal margins (free of carcinoma vs positive), perineural invasion (no vs yes), smoking status ( 10 pack-years vs > 10 pack-years), and tumor classification (T1/T2 vs T3/T4). To profile the risk of death, a recursive partitioning analysis (RPA) was used as an exploratory analysis. The “rpart” library in the R package was used to fit a regres- sion tree with the overall survival data. 39,40 In evaluating prognostic factors for overall survival, the predictors used in the multivariable Cox proportional hazards model were included in the building of the tree. All analyses were

standard fraction or accelerated fraction radiotherapy. The authors provided strong evidence that HPV-related oro- pharyngeal SCC is a unique disease entity with improved survival outcomes. They also classified patients with oro- pharyngeal SCC as having either a low, intermediate, or high-risk of death dependent upon HPV status, smoking history, neck disease, and primary tumor classification (all of which were independent predictors of survival). The 3-year survival rates were 93.0%, 70.8%, and 46.2%, respectively. The data from RTOG 0129 suggests that less intense therapy may be warranted for the low-risk group of patients and more intense therapy may be needed for the high-risk group. The intermediate group of patients, which includes 36% of all HPV-positive patients, should not be deintensified but clearly have poorer overall survival outcomes than the low-risk group because of their smoking status and extensive neck disease. Nonsurgically treated patient survival and functional outcomes for oropharyngeal SCC have been well- documented; however, outcomes data for patients treated with primary surgery is sparse. Since the reports by Par- sons et al, 5,6 surgical and reconstructive technology has dramatically advanced and improved functional outcomes. The use of transoral laser microsurgery and transoral robotic surgery (TORS) have allowed surgeons to access tumors without disrupting normal anatomy, while provid- ing superior visualization of tumor margins. 27–32 Further- more, when open procedures are necessary, free flap surgeons are able to provide superior cosmetic and func- tional outcomes. In addition, surgical resection may be a way to deintensify therapy for patients in the lowest or intermediate risk categories by obviating the need for concurrent chemoradiotherapy. The purpose of this study was to determine the impact of primary surgery in the treatment of oropharyngeal SCC. Predictors of survival will be determined and func- tional outcomes will be reported. In addition, survival and functional outcomes will be compared between open sur- gery and transoral surgical approaches for tumor extirpation. MATERIALS AND METHODS After institutional review board approval, a prospective database of patients with head and neck cancer treated with primary surgery was assembled and continually maintained. This study was retrospective in nature and exempt from consent. The database was searched for patients with oropharyngeal SCC treated from January 1, 2002, to August 31, 2012. Patients who were treated with primary surgery for histologically confirmed SCC were assessed for eligibility. Patients who were previously untreated, had tissue available for analysis, and had avail- able clinical follow-up data were included in the study. For each patient, demographic data, complete medical history, pathology, and follow-up were recorded and veri- fied in real time. Survival data was ascertained through medical record review and confirmed through tumor registry files and the Social Security Death Index data. The type of surgery performed was recorded and classi- fied as: (a) TORS; (b) transoral nonrobotic; (c) open transcervical (ie, suprahyoid pharyngotomy, lateral phar- yngotomy); (d) mandibulotomy; or (e) composite resec-

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