Association of Postoperative Radiotherapy With Survival in Patients With N1 Oral Cavity and Oropharyngeal Squamous Cell Carcinoma | Head and Neck Cancer | JAMA Otolaryngology–Head & Neck Surgery | JAMA Network
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Figure 1.  Temporal Trends in the Use of Postoperative Radiotherapy (PORT) for the Study Population
Temporal Trends in the Use of Postoperative Radiotherapy (PORT) for the Study Population

Study patients had pT1N1 and pT2N1 squamous cell carcinoma (SCC) of the oral cavity and oropharynx.

Figure 2.  Kaplan-Meier Survival Curves for the Study Population
Kaplan-Meier Survival Curves for the Study Population

PORT indicates postoperative radiotherapy; SCC, squamous cell carcinoma.

Table 1.  Baseline Characteristics
Baseline Characteristics
Table 2.  Cox Multivariate Regression Analysis Predicting the Hazard of Mortalitya
Cox Multivariate Regression Analysis Predicting the Hazard of Mortalitya
Table 3.  Cox Models Predicting Hazard of Mortality Stratified by Tumor Stagea
Cox Models Predicting Hazard of Mortality Stratified by Tumor Stagea
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Vokes  EE, Weichselbaum  RR, Lippman  SM, Hong  WK.  Head and neck cancer.  N Engl J Med. 1993;328(3):184-194.PubMedGoogle ScholarCrossref
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Kokal  WA, Neifeld  JP, Eisert  D,  et al.  Postoperative radiation as adjuvant treatment for carcinoma of the oral cavity, larynx, and pharynx: preliminary report of a prospective randomized trial.  J Surg Oncol. 1988;38(2):71-76.PubMedGoogle ScholarCrossref
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Mishra  RC, Singh  DN, Mishra  TK.  Post-operative radiotherapy in carcinoma of buccal mucosa: a prospective randomized trial.  Eur J Surg Oncol. 1996;22(5):502-504.PubMedGoogle ScholarCrossref
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Lundahl  RE, Foote  RL, Bonner  JA,  et al.  Combined neck dissection and postoperative radiation therapy in the management of the high-risk neck: a matched-pair analysis.  Int J Radiat Oncol Biol Phys. 1998;40(3):529-534.PubMedGoogle ScholarCrossref
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Kao  J, Lavaf  A, Teng  MS, Huang  D, Genden  EM.  Adjuvant radiotherapy and survival for patients with node-positive head and neck cancer: an analysis by primary site and nodal stage.  Int J Radiat Oncol Biol Phys. 2008;71(2):362-370.PubMedGoogle ScholarCrossref
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Lavaf  A, Genden  EM, Cesaretti  JA, Packer  S, Kao  J.  Adjuvant radiotherapy improves overall survival for patients with lymph node-positive head and neck squamous cell carcinoma.  Cancer. 2008;112(3):535-543.PubMedGoogle ScholarCrossref
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Shrime  MG, Gullane  PJ, Dawson  L,  et al.  The impact of adjuvant radiotherapy on survival in T1-2N1 squamous cell carcinoma of the oral cavity.  Arch Otolaryngol Head Neck Surg. 2010;136(3):225-228.PubMedGoogle ScholarCrossref
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Jäckel  MC, Ambrosch  P, Christiansen  H, Martin  A, Steiner  W.  Value of postoperative radiotherapy in patients with pathologic N1 neck disease.  Head Neck. 2008;30(7):875-882.PubMedGoogle ScholarCrossref
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Luryi  AL, Chen  MM, Mehra  S, Roman  SA, Sosa  JA, Judson  BL.  Treatment factors associated with survival in early-stage oral cavity cancer: analysis of 6830 cases from the national cancer data base.  JAMA Otolaryngol Head Neck Surg. 2015;141(7):593-598.PubMedGoogle ScholarCrossref
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Sanabria  A, Carvalho  AL, Vartanian  JG, Magrin  J, Ikeda  MK, Kowalski  LP.  Comorbidity is a prognostic factor in elderly patients with head and neck cancer.  Ann Surg Oncol. 2007;14(4):1449-1457.PubMedGoogle ScholarCrossref
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Huang  SH, O’Sullivan  B, Waldron  J,  et al.  Patterns of care in elderly head-and-neck cancer radiation oncology patients: a single-center cohort study.  Int J Radiat Oncol Biol Phys. 2011;79(1):46-51.PubMedGoogle ScholarCrossref
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Chen  MM, Roman  SA, Yarbrough  WG, Burtness  BA, Sosa  JA, Judson  BL.  Trends and variations in the use of adjuvant therapy for patients with head and neck cancer.  Cancer. 2014;120(21):3353-3360.PubMedGoogle ScholarCrossref
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Gillison  ML, Chaturvedi  AK, Anderson  WF, Fakhry  C.  Epidemiology of human papillomavirus-positive head and neck squamous cell carcinoma.  J Clin Oncol. 2015;33(29):3235-3242.PubMedGoogle ScholarCrossref
Original Investigation
From the American Head and Neck Society
December 2016

Association of Postoperative Radiotherapy With Survival in Patients With N1 Oral Cavity and Oropharyngeal Squamous Cell Carcinoma

Author Affiliations
  • 1Department of Otolaryngology–Head and Neck Surgery, Stanford University, Palo Alto, California
  • 2Department of Radiation Oncology, Stanford University, Palo Alto, California
  • 3Department of Otolaryngology, Palo Alto Veterans Administration, Palo Alto, California
JAMA Otolaryngol Head Neck Surg. 2016;142(12):1224-1230. doi:10.1001/jamaoto.2016.3519
Key Points

Question  Should postoperative radiotherapy (PORT) be used for pT1N1 or pT2N1 oral cavity (OC) squamous cell carcinoma (SCC) and oropharyngeal (OP) SCC?

Findings  In this retrospective national study of 1467 patients with pT1N1 or pT2N1 OC SCC and 790 patients with OP SCC without adverse pathologic features, PORT was associated with improved overall survival in patients younger than 70 years and those with pT2 disease.

Meaning  PORT should be an important consideration, even for low-risk patients with OC and OP SCC and especially for younger patients with pT2N1 disease.

Abstract

Importance  The guidelines for head and neck cancer recommend consideration of adjuvant postoperative radiotherapy (PORT) for patients with pT1N1 or pT2N1 disease in the absence of other adverse features. This recommendation was recently changed for oropharyngeal (OP) squamous cell carcinoma (SCC).

Objective  To examine the use and outcomes of PORT for N1 OP SCC and oral cavity (OC) SCC.

Design, Setting, and Participants  This retrospective cohort study identified 1467 adult patients with OC SCC and 790 patients with OP SCC with pT1N1 or pT2N1 disease in the absence of other adverse features from the National Cancer Database from January 1, 2004, to December 31, 2013. Patients who received adjuvant chemotherapy or palliative radiotherapy or who had adverse pathologic features were excluded. Statistical analysis included χ2 tests and Cox proportional hazards regression analysis. Data were analyzed from November 10, 2015, to June 30, 2016.

Main Outcomes and Measures  Overall survival.

Results  Of the 1467 patients with OC SCC (842 men [57.4%]; 625 women [42.6%]; mean [SD] age, 61.3 [13.8] years), 740 (50.4%) received PORT. Of the 790 patients with OP SCC (584 men [73.9%]; 206 women [26.1%]; mean [SD] age, 58.2 [10.3] years), 449 (56.8%) received PORT. After controlling for patient demographics, pathologic characteristics, and hospital-level variables, PORT was associated with improved overall survival for patients with OC SCC (hazard ratio [HR], 0.76; 95% CI, 0.63-0.92) and OP SCC (HR, 0.62; 95% CI, 0.41-0.92) with pN1 disease without adverse features. On stratified analysis, this association persisted for patients younger than 70 years (OC SCC HR, 0.77; 95% CI, 0.61-0.97; OP SCC HR, 0.48; 95% CI, 0.31-0.75) and those with pT2 disease (OC SCC HR, 0.64; 95% CI, 0.43-0.96; OP SCC HR, 0.56; 95% CI, 0.32-0.95), but there was no association with overall survival among patients 70 years or older (OC SCC HR, 0.78; 95% CI, 0.58-1.06; OP SCC HR, 1.55; 95% CI, 0.63-3.82) and those with pT1 disease (OC SCC HR, 0.80; 95% CI, 0.60-1.07; OP SCC HR, 0.66; 95% CI, 0.35-1.24).

Conclusions and Relevance  PORT may be associated with improved survival in patients with pN1 OC and OP SCC, especially in those younger than 70 years or those with pT2 disease.

Introduction

The involvement of the cervical lymph nodes is one of the most important prognostic factors in head and neck cancer, and locoregional failure is the most common site of recurrence.1 To reduce the risk for local and regional recurrence, postoperative radiotherapy (PORT) is added after surgical resection for select patients with high-risk features. Although limited randomized evidence of the benefits of PORT exists,2,3 retrospective reviews and comparison with historical controls have shown reductions in local and regional failure and improvement in survival.4-8

Based on this evidence, the National Comprehensive Cancer Network (NCCN) recommends PORT for patients with extracapsular spread, positive margins, lymphovascular invasion, perineural invasion, pT3 to pT4 disease, and pN2 to pN3 disease.9 However, for patients without these risk features (including those with pT1N1 or pT2N1 disease), the recommendation is for the treating physicians to consider PORT. Starting in 2014, the NCCN no longer recommended consideration of PORT for those with oropharyngeal squamous cell carcinoma (OP SCC).10,11

The benefit of PORT for pN1 disease without adverse features is unclear.8 Prior investigations have been primarily limited to single-institution studies4,7,8,12,13 with limited numbers or did not exclude patients with adverse features.5,14 The purpose of our study is to examine the use of PORT for patients with pN1 oral cavity (OC) and OP SCC without adverse features and to determine whether PORT is associated with survival. We hypothesized that PORT is associated with improved overall survival and that this benefit would be greater in patients with OC SCC than in those with OP SCC.

Methods
Data Source and Study Participants

For this study, we used patient data from the National Cancer Database (NCDB) from January 1, 2004, to December 31, 2013. The NCDB is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. The NCDB includes cancer registry data from more than 1500 Commission on Cancer–accredited programs nationwide.15 The NCDB covers more than 70% of incident cases of cancer in the United States.15 Our retrospective study was granted an exemption from the Stanford University institutional review board.

Patients with OC and OP SCC were identified using the International Classification of Diseases for Oncology, Third Edition (ICD-O-3) topography codes for OC (C00.0-C00.6, C00.8-C00.9, C02.0-C2.3, C02.8-C03.1, C03.9-C04.1, C04.8-C05.2, C05.8-C06.2, and C06.8-C06.9) and OP (C09.0-C09.1, C09.8-C09.9, C10.0, C10.2-10.4, C10.8-C10.9, C01.9, and C02.4). All adult patients (aged ≥18 years) with a pathologic diagnosis of T1N1 or T2N1 SCC were included (ICD-O-3 codes 8052, 8070-8076, 8083-8084, 8094, and 8560). Pathologic staging was based on the American Joint Committee on Cancer edition that corresponded to their year of diagnosis; therefore, the sixth16 and seventh17 editions of the American Joint Committee on Cancer staging guidelines were used. No changes were made to the classification criteria of T1 and T2 OC and OP SCC or the N classification criteria between the editions.

We excluded patients with any adverse pathologic features, including positive surgical margins, extracapsular extension, and lymphovascular invasion. We excluded all patients with unknown pathologic T and N staging data and margin status. Lymphovascular invasion data were only present from 2010 to 2013; therefore we excluded all patients with the presence of lymphovascular invasion during that period. Extracapsular extension was incompletely coded in the NCDB. We excluded all patients with known extracapsular extension. We also excluded all patients who received chemotherapy and treatment with palliative intent. Perineural invasion could not be excluded because the NCDB does not contain these data.

Demographic variables included sex, age, race, comorbidities, insurance status, socioeconomic status, and region. Age was classified into 4 groups (<50, 50-59, 60-69, and ≥70 years). Race was classified as white, black, and other. Comorbidities were grouped into 0, 1, and 2 or more based on the Charlson-Deyo comorbidity index (higher scores indicate more comorbidities).18 Insurance status was defined as not insured, private or managed care, Medicare or Medicaid, and unknown. Socioeconomic status was approximated using income and educational level data based on each patient’s home address. Income was the estimated median income for the patient’s zip code and was grouped into quartiles; we compared the highest quartile group (≥$46 000) with all other quartiles. Educational level was based on the percentage of adults in the patient’s zip code who did not graduate from high school, and the highest quartile group (<14%) was compared with all other groups. Clinical and hospital-level variables included pathologic T category, PORT, package time (calculated as the time in weeks from the day of surgery to the last day of radiotherapy), and hospital type. Hospital type was grouped into academic centers and community centers (including nonacademic cancer centers).

Our primary outcome of interest was overall survival. Survival in years was calculated from the date of diagnosis to death, and patients were censored at the last date the patient was known to be alive or December 31, 2013, whichever came first.

Statistical Analysis

Data were analyzed from November 10, 2015, to June 30, 2016. All statistical analysis was performed using SPSS software (version 23.0; SPSS Inc). Bivariate analysis using χ2 and 2-sided t tests were used to analyze our categorical and continuous variables, respectively. Kaplan-Meier survival analysis and Cox proportional hazards regression analysis were used to identify factors associated with overall survival. Our adjusted overall survival was calculated using the average covariate method. Hazard ratios (HR) and 95% CIs were calculated for the strength of association. All tests were 2-sided, and P < .05 was considered to be statistically significant.

Results
Overview

From January 1, 2004, to December 31, 2013, we identified 198 417 adult patients with OC or OP cancer. Of these, 184 145 had SCC, and 9281 patients had surgery and pN1 disease. When only patients with pT1 and pT2 disease were included, 6235 patients remained. After excluding all patients with adverse pathologic features (extracapsular extension, positive margins, lymphovascular invasion, and pT3 or pT4 disease), 3725 patients remained. Patients who received neoadjuvant radiotherapy, any chemotherapy, or any treatment with palliative intent were also excluded, resulting in 2257 patients. Of these, 1467 had OC SCC (842 men [57.4%]; 625 women [42.6%]; mean [SD] age, 61.3 [13.8] years) and 790 had OP SCC (584 men [73.9%]; 206 women [26.1%]; mean [SD] age, 58.2 [10.3] years).

From 2004 to 2013, 50.4% of patients with OC SCC and 56.8% of patients with OP SCC received PORT. The annual proportions of patients with pT1N1 and pT2N1 tumors receiving PORT fluctuated from 40.6% to 60.0% for those with OC SCC and 43.6% to 66.7% for those with OP SCC (Figure 1). We observed no significant decline in PORT use for OC SCC; however, for OP SCC, linear regression demonstrated a negative trend over time with an annual decrease in the proportion of PORT use by 2 percentage points (R2 = 0.89; P = .001).

Oral Cavity SCC

Among patients with OC SCC, those who had PORT and those who did not have adjuvant therapy had similar baseline characteristics in terms of sex, race, and socioeconomic status (Table 1). Patients with pT2 disease (55.5% vs 44.5%; P < .001) and a Charlson-Deyo comorbidity index of 0 (52.4% vs 47.6%; P = .01) were more likely to have PORT than no adjuvant therapy. In community centers, 58.1% of patients with pT1N1 and pT2N1 disease had PORT, whereas only 45.9% of similar patients treated at academic centers had PORT (P < .001). Median package time for PORT was 13.9 (interquartile range, 12.1-16.0) weeks and did not vary significantly by T stage (P = .98).

We analyzed the association between PORT and overall survival in our OC SCC cohort. On multivariate analysis, PORT was associated with improved overall survival for patients with pN1 disease without adverse features (HR, 0.76; 95% CI, 0.63-0.92) (Table 2). For patients with OC SCC, being 70 years or older, having a Charlson-Deyo comorbidity index of at least 2, and having pT2 disease were also independently associated with decreased overall survival. We found no difference in overall survival for patients with OC SCC treated at academic centers compared with those treated at community centers. Figure 2A demonstrates Kaplan-Meier survival curves for patients with and without PORT. The median follow-up was 5.2 (interquartile range, 3.2-7.2) years, and the unadjusted 5-year overall survival was 58.8% with PORT and 54.4% without PORT (P = .007). After adjusting for demographic, clinical, and pathologic variables, the 5-year overall survival was 60.8% with PORT and 52.0% without PORT for patients with OC SCC.

Oropharyngeal SCC

For patients with OP SCC, male patients were more likely to have PORT than female patients (59.1% vs 50.5%; P = .03). Patients 70 years or older (42.2%) were less likely to have PORT than patients younger than 50 years (59.7%), 50 to 59 years (57.7%), and 60 to 69 years (60.3%) (P = .01). We found no difference in race, comorbidities, insurance status, and socioeconomic markers between patients who had PORT and those who had no adjuvant therapy. In community centers, 65.0% of patients had PORT, while in academic centers, 50.2% of patients had PORT (P < .001). There was no difference in the use of PORT between patients who had transoral robotic surgery and those who did not (43.6% vs 44.4%; P = .91). Patients with tonsil cancer had similar rates of PORT as those with primary tumors on the base of the tongue (59.8% vs 53.3%; P = .10). Median package time for PORT was 13.1 (interquartile range, 11.6-15.1) weeks, and we found no difference in package time by T stage (P = .60).

PORT was independently associated with improved overall survival for patients with OP SCC (HR, 0.62; 95% CI, 0.41-0.92). A Charlson-Deyo comorbidity index of at least 2 and pT2 disease were independently associated with worse overall survival. Being 70 years or older was not significantly associated with decreased overall survival. The median follow-up was 4.8 (interquartile range, 2.8-7.1) years and the unadjusted 5-year overall survival was 85.1% for patients with PORT compared with 74.7% for those without PORT (P < .001). The 5-year adjusted overall survival was 86.3% for patients with PORT and 78.8% without PORT (Figure 2B).

Subanalysis

After stratification by pathologic T stage, patients with pT1 OC and OP SCC did not demonstrate an association between PORT and overall survival. In patients with pT2 disease, PORT was independently associated with improved survival for patients with OC SCC (HR, 0.64; 95% CI, 0.43-0.96) and OP SCC (HR, 0.56; 95% CI, 0.32-0.95) (Table 3).

We also conducted a stratified analysis by age group (<70 and ≥70 years) to assess whether or not PORT is associated with a survival benefit in older patients, given that age is an important negative prognostic factor. PORT in patients younger than 70 years was associated with improved overall survival among those with OC SCC (HR, 0.77; 95% CI, 0.61-0.97) and OP SCC (HR, 0.48; 95% CI, 0.31-0.75). For patients with OC SCC and OP SCC who were 70 years or older, PORT was not associated with improved overall survival.

We addressed the effect of immortal time bias against the patients who did not receive PORT by conducting a subset analysis limited only to patients who were alive 90 days after surgery. This analysis excluded an additional 31 patients with OC SCC and 16 with OP SCC. Akin to our results for our overall cohort, the 5-year overall survival for patients with OC SCC was 55.5% for those without PORT and 58.8% for patients with PORT (P = .03); for patients with OP SCC, the 5-year overall survival was 75.4% for patients without PORT and 85.4% for those with PORT (P < .001).

Discussion

This study is a retrospective review of a large national cancer database to evaluate the effect of PORT on patients with pT1N1 and pT2N1 disease without adverse features. Our results demonstrate that the use of PORT was associated with improved survival for patients with OC and OP SCC, especially those younger than 70 years and those with pT2 disease. To our knowledge, our study is the first national analysis of use of and outcomes after PORT in low-risk patients with pN1 OC and OP SCC without adverse pathologic features.

The study included patients treated from 2004 to 2013, during which time the NCCN guidelines considered PORT to be optional for patients with pN1 disease without adverse features. The proportion of patients who received PORT during that time frame has been relatively stable for patients with OC SCC, whereas it decreased for patients with OP SCC from 66.7% in 2004 to 43.6% in 2013. In 2014, the guidelines no longer recommended PORT for patients with N1 OC SCC without adverse features.

Prior studies investigating the benefit of PORT did not exclude patients with adverse pathologic features. For example, the study by Chen et al12 analyzed 59 patients with pT1 or pT2 and pN0 or pN1 OC SCC and found improved 5-year disease-specific survival in those who had PORT compared with those without PORT (81.2% vs 53.0%; P = .03), but no difference in overall survival (77.0% vs 70.5%; P = .36). Using the Surveillance, Epidemiology, and End Results (SEER) database, Kao et al5 demonstrated no difference in 5-year overall survival between patients with N1 OC SCC with and without PORT (38.7% vs 36.0%; P = .23). Shrime et al7 analyzed 1539 patients in the SEER database with only T1N1 and T2N1 OC SCC and found that 78.6% had PORT and that PORT was associated with improved 5-year overall survival (54.2% vs 41.4%; P < .001).

Our results corroborate prior results by Kao et al5 in patients with N1 OP SCC, including those who may have had adverse pathologic features. Kao et al5 demonstrated improved 5-year overall survival in patients with N1 OP SCC (67.9% vs 65.0%; P = .003), and the magnitude of the risk reduction for death was greater for patients with OP SCC relative to OC SCC (HR, 0.72; P < .001).5 Jäckel et al8 analyzed 118 patients with pN1 head and neck cancer without extracapsular extension, including 22 patients with OC SCC and 34 with OP SCC, and found decreased 3-year neck recurrence rates in the patients with PORT compared with those who had surgery alone (2.9% vs 11.2%; P = .09). However, no difference was found in the 5-year overall survival rates among patients with T1N1 and T2N1 disease who underwent surgery alone and those who underwent PORT (60.7% and 63.6%; P = .62).8 That study did not exclude patients with other adverse features beyond extracapsular extension.

The present study is important because patients believed to have low-risk disease, defined by pN1 involvement and lack of adverse risk factors, demonstrated an association with improved survival when treated with PORT. Although in the context of this retrospective cohort study, it is difficult to prove that PORT directly led to improved survival, the magnitude of the HRs is clinically significant. For patients with OC SCC, the current NCCN guidelines recommend consideration of PORT; and for patients with OP SCC, PORT is no longer recommended. This study suggests that we should continue to study the effect of this change in the NCCN guidelines. Avoiding the toxic effects of PORT in a low-risk human papillomavirus (HPV)–positive N1 OP SCC is important and aligns with changes toward de-escalating therapy for these patients. Our study urges caution in de-escalating off trial for patients with pT2N1 OP SCC or those who are younger than 70 years of age and suggests that further studies are needed.

Stratifying our analysis by age demonstrated no association between PORT and improved overall survival for patients 70 years or older. Limited data are available on the tolerance and benefit of PORT in elderly patients. Comorbidities are more common in the elderly population, with 1 study19 demonstrating that 75% of patients with head and neck cancer who are 70 years or older have comorbidities. Huang et al20 determined that age was associated with worse cancer-specific survival in patients with head and neck cancer, and elderly patients tended to receive lower doses of radiation, perhaps owing to their comorbidities. In elderly patients with head and neck cancer who received definitive radiotherapy, no evidence of impaired treatment tolerance was found.20

In our study population, patients treated at community hospitals were more likely to receive PORT compared with those treated at academic medical centers. However, academic centers were not independently associated with decreased survival on multivariate analysis. A national study looking at the use of adjuvant therapy for patients with head and neck cancer with adverse pathologic features21 demonstrated that patients were more likely to receive adjuvant therapy at community centers than academic centers (54.2% vs 45.9%; P < .001).

Limitations

Limitations to our study include those inherent to retrospective database research, including possible coding and abstraction errors. In addition, other high-risk features, such as smoking and HPV-negative status, may not have been captured in the NCDB but may also identify patients who may benefit from PORT. We do not have sufficient data regarding HPV status in our OP SCC group; however, studies suggest that during this time frame, more than 70% of patients with OP SCC would be positive for HPV.22,23 Among the limited group of 205 patients for whom we have information from 2010 to 2013, 169 (82.4%) of our patients were positive for HPV. We also do not have sufficient data on depth of invasion for patients with OC SCC. We were unable to exclude all patients with extracapsular extension and lymphovascular invasion because data were incompletely coded for these variables in the NCDB. We were also unable to exclude patients with perineural invasion, which is an important adverse feature, because the NCDB does not include data on perineural invasion. However, these confounders would likely worsen survival in the PORT group. We did not exclude any patients with extended package times between surgery and completion of PORT to account for how radiotherapy is delivered in practice. The NCDB also does not have data on locoregional recurrence, reoperation, or disease-specific survival.

Conclusions

PORT may be associated with improved survival in patients with N1 OC and OP SCC without adverse pathologic features. Our results suggest that PORT should be an important consideration for even low-risk patients younger than 70 years with OC and OP SCC, particularly those with T2N1 disease.

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Article Information

Corresponding Author: Vasu Divi, MD, Department of Otolaryngology–Head and Neck Surgery, Stanford University, 900 Blake Wilbur Dr, Third Floor, Stanford, CA 94305 (vdivi@stanford.edu).

Accepted for Publication: September 17, 2016.

Published Online: November 10, 2016. doi:10.1001/jamaoto.2016.3519

Author Contributions: Drs Chen and Divi had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Chen, Hara, Divi.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Chen, Divi.

Critical revision of the manuscript for important intellectual content: Chen, Harris, Hara, Sirjani, Divi.

Statistical analysis: Chen, Harris.

Administrative, technical, or material support: Divi.

Study supervision: Harris, Hara, Divi.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Disclaimer: The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical method used or the conclusions drawn from these data by the investigator.

Previous Presentation: This study was presented at the American Head & Neck Society Ninth International Conference on Head and Neck Cancer; July 19, 2016; Seattle, Washington.

References
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Vokes  EE, Weichselbaum  RR, Lippman  SM, Hong  WK.  Head and neck cancer.  N Engl J Med. 1993;328(3):184-194.PubMedGoogle ScholarCrossref
2.
Kokal  WA, Neifeld  JP, Eisert  D,  et al.  Postoperative radiation as adjuvant treatment for carcinoma of the oral cavity, larynx, and pharynx: preliminary report of a prospective randomized trial.  J Surg Oncol. 1988;38(2):71-76.PubMedGoogle ScholarCrossref
3.
Mishra  RC, Singh  DN, Mishra  TK.  Post-operative radiotherapy in carcinoma of buccal mucosa: a prospective randomized trial.  Eur J Surg Oncol. 1996;22(5):502-504.PubMedGoogle ScholarCrossref
4.
Lundahl  RE, Foote  RL, Bonner  JA,  et al.  Combined neck dissection and postoperative radiation therapy in the management of the high-risk neck: a matched-pair analysis.  Int J Radiat Oncol Biol Phys. 1998;40(3):529-534.PubMedGoogle ScholarCrossref
5.
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