2017 Section 7 Green Book

S URGICAL MANAGEMENT OF OROPHARYNGEAL SCC

TABLE 4. Percentage of patients with gastrostomy tube present at 12 months postsurgery.

gastrostomy tube dependence compared with patients undergoing a transoral approach. Patients with T1 and T2 tumors who underwent a transoral resection had a gastros- tomy tube present at 1 year in 7.84% of the cases, regard- less of HPV status. These numbers are remarkably similar to other surgical trials and reinforce that higher rates of gastrostomy tube presence are primarily seen with T3 and T4 tumors (9.52% for the transoral approach and 33.33% for the open approach). This number compares favorably to gastrostomy tube and dysphagia rates in chemoradia- tion trials. Best et al 23 reported a 19% rate of stricture and Shiley et al 26 reported that 47% of patients continue to require gastrostomy tube feedings even 1 year after chemoradiotherapy. Even in studies evaluating the use of intensity-modulated radiotherapy, sparing pharyngeal con- strictors, 4 of 73 patients (5.6%) report significant change in diet and 1 of 73 patients (1.3%) was exclusively gas- trostomy tube dependent. In quality of life surveys, a sharp deterioration of swallowing is seen postchemoradio- therapy treatment and this improves slightly between 3 and 12 months posttherapy. Only 15.6% of patients reported a normal diet at 1 year postchemoradiotherapy, 57% have objective swallowing impairment, and 23% exhibit silent aspiration on modified barium swallowing studies. 22 In this patient cohort, postoperative concurrent chemo- radiotherapy was delivered for “high-risk patients” as defined by the paired New England Journal of Medicine manuscripts published in 2004. 34,41 Based on our analysis, when controlling for other variables, there was no signifi- cant difference in survival between patients treated with postoperative radiation versus those treated with concur- rent chemoradiation. With the recent emphasis on treat- ment deintensification for HPV-positive patients, transoral surgery with postoperative radiotherapy alone may be an effective strategy to pursue based on these results. On the other hand, patients with HPV-negative tumors, T3/T4 primary, and ECS have unusually poor outcomes from both a survival and functional perspective. Intensification of nonsurgical therapy may be the best treatment options to consider in this group of patients. The retrospective nature of this study could lend to selection biases, such as changing treatment patterns and techniques. Another weakness of this study was the lack of data on disease-specific, progression-free, and disease- free survival. However, this study is the largest analysis of primary surgical therapy for oropharyngeal SCC. We were able to control for many factors to arrive at the sig- nificant results of this study, demonstrating excellent sur- vival and functional outcomes for selected populations and treatment modalities of oropharyngeal SCC. This analysis further supports the future use and study of pri- mary surgical therapy for certain cohorts of oropharyngeal SCC, particularly in our attempts at deintensifying ther- apy for HPV-positive patients. REFERENCES 1. Chaturvedi AK, Anderson WF, Lortet–Tieulent J, et al. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol 2013;31:4550–4559. 2. Gillison ML, D’Souza G, Westra W, et al. Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16- negative head and neck cancers. J Natl Cancer Inst 2008;100:407–420.

Surgical approach

T1/T2

T3/T4

Transoral

7.84%

9.52% 33.33%

Open

34.0%

HPV-negative and HPV-positive patients had distinct independent predictors of survival. The most important predictor of survival in HPV-negative patients was the presence of ECS. On the other hand, survival in HPV- positive patients was associated with the surgical approach (transoral vs open), and whether or not negative margins were achieved. Specifically, in the HPV-positive cohort, those with transoral resection tended to have more favorable outcomes; patients resected via the open approach were over 3 times more likely to die than those treated transorally. When controlling for all factors, including T classification, smoking status, etc., patients who underwent transoral resection had improved survival. Our multivariable analysis confirmed that the surgical approach was a significant independent predictor of over- all survival and not simply a surrogate marker for advanced disease. This finding may reflect the greater morbidity and swallowing dysfunction associated with open approaches, placing these patients at greater risk of postoperative aspiration pneumonia. Without randomiza- tion to surgical approach, however, potential unidentified confounders cannot be ruled out. RPA of the entire patient population revealed that HPV status was the major determinant of overall survival. In HPV-positive patients, the next most important determi- nant of survival was the surgical approach utilized fol- lowed by the pathologic factors of margin status and perineural invasion. In the HPV-negative patient popula- tion, the surgical approach was not a significant predictor of outcome, but rather the presence of ECS, followed by the T classification of the primary tumor. If the RPA trees are pruned further, 3 survival outcome groups emerge that may be deemed: low-, intermediate-, and high-risk (see Figure 2). HPV-positive patients who are resected transorally have the lowest risk of death (15 deaths out of 124 patients; 87.9% survival). For HPV-positive patients undergoing transoral resection, the presence of perineural invasion was a significant prognostic factor, as shown in Figure 2A, which is contrary to the study by Haughey and Sinha, 27 who did not find perineural invasion to be a significant prognostic factor in surgically treated p16- positive patients. The intermediate-risk group consists of those patients who are HPV-positive and resected with an open approach and negative margins (60.3% survival), HPV-negative patients with no ECS (58.2% survival), or HPV-negative T1/T2 tumors with ECS (45.5% survival). Finally, the high-risk group consists of HPV-positive tumors resected with an open approach and positive mar- gins (25.0% survival) and HPV-negative T3/T4 tumors with ECS (13.8% survival). To complement the survival data, functional outcomes were also investigated. As shown in Table 4, patients undergoing an open approach had much higher rates of

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