Analysis of Process-Related Quality Metrics and Survival of Patients with Oral Cavity Squamous Cell Carcinoma

Abstract

Objective

To analyze the association of prior reported key quality metrics—neck dissection ≥18 nodes, radiation oncology referral for stage III/IV disease, unplanned surgery ≤14 days, and unplanned readmission ≤30 days—with disease-free survival (DFS) and overall survival (OS) in oral cavity cancer (OCC).

Study Design

A retrospective chart review.

Setting

A tertiary care center from 1995 to 2016.

Subjects and Methods

Data from patients with OCC who underwent primary surgery were studied. The association of quality metrics and pathology with DFS/OS was determined by Cox proportional hazards regression analysis.

Results

A total of 514 patients were included, and 398 (77.4%) underwent elective neck dissection. Key metrics were not associated with DFS on analysis, but higher pathologic stage and extracapsular extension (ECE) were. When stratified by stage, unplanned readmission within 30 days was associated with decreased survival on multivariate analysis (HR = 0.40; 95% CI, 0.20-0.85; P = .02) for patients with clinical stage III or IV disease. ECE was associated with decreased survival among these patients as well. Neck dissection with ≤18 nodes (HR = 0.62; 95% CI, 0.44-0.86; P = .004) and unplanned surgery within 14 days (HR = 0.56; 95% CI, 0.32-0.96; P = .03) were associated with decreased survival on univariate analysis but not on multivariate analysis. ECE and higher-stage disease were associated with decreased OS on multivariate analysis.

Conclusion

In this study, aggressive pathology, rather than adherence to key quality metrics, was associated with lower DFS and OS among patients with OCC. More studies are needed to elucidate the association of quality metrics with survival.

Keywords

oral cavity squamous cell carcinoma quality metrics compliance survival

Quality measures have generated increased attention due to the connection to physician and hospital reimbursements in addition to being central to hospital ratings. Process-related quality metrics are those associated with the care that the patient actually receives and are measures that the health care provider can potentially target and have the most impact.^1,2 However, there remains only modest evidence that these quality metrics are actually associated with improved patient outcomes.³ In fact, adherence to these metrics can sometimes have unintended consequences that can be expensive or detrimental to the patient. For example, for patients with suspected community-acquired pneumonia, national treatment guidelines endorsed by the Centers for Medicare and Medicaid Services led to unnecessary prescribing of antibiotics and were not associated with decreased mortality.⁴

Consequently, there is a drive to determine patient-centered, evidence-based quality metrics for individual specialties.³ Nationally endorsed quality metrics exist in other areas of health care, such as trauma surgery, surgical infection prevention, and breast cancer treatment.^5,6 An effort is being made to define similar metrics for head and neck cancer surgery,⁷ but difficulty in showing an association between these metrics and improved patient outcomes still exists. For example, a study examining patients with laryngeal squamous cell carcinoma did not show any association between National Comprehensive Cancer Network guidelines and survival.⁸ In 2007, the American Head and Neck Society proposed process-related quality metrics for the treatment of oral cavity squamous cell carcinoma (OCSCC), as this particular subsite is often treated primarily with surgery.⁹ However, it is still unknown if compliance with these metrics is actually associated with improved patient outcomes.

In an effort to answer this question, Graboyes et al demonstrated that compliance with 4 key process-related quality metrics was associated with improved survival for patients with OCSCC who were treated definitively with surgery at a single institution.¹⁰ These metrics included lymph node dissection with yield ≥18 nodes, referral to radiation oncology for stage III or IV disease, unplanned surgery within 14 days of the index surgery, and unplanned readmission within 30 days. The authors called for validation of their results in an independent population to determine if they could become the basis for nationally endorsed quality metrics for head and neck surgery. The objective of this study was to examine this “clinical care signature” and to determine if compliance with key process-related quality metrics is associated with improved disease-free survival (DFS) and overall survival (OS) among patients with surgically treated OCSCC at a tertiary care institution.

Methods

Patient Data

The Cleveland Clinic Institutional Review Board approved this study, and patient data were de-identified after chart review was completed and data extracted. A retrospective chart review was performed of all patients with OCSCC treated at the Cleveland Clinic who underwent definitive surgery with or without adjuvant treatment from January 1995 to October 2016. Patients with previously treated head and neck cancer were excluded, and 514 patients met inclusion criteria. Data regarding demographics, treatment, pathologic characteristics, surveillance, and mortality were extracted. Selection of quality metrics was based on the previous study by Graboyes et al,¹⁰ which was in turn based on recommendations made by the American Head and Neck Society and the National Comprehensive Cancer Network. Data regarding adherence to the clinical care signature as well as other quality metrics were extracted. Data regarding tobacco cessation counseling and dental referral could not be extracted due to insufficient documentation in the electronic medical record.

Outcomes and Survival Analysis

Outcomes examined included DFS and OS. DFS was calculated from the day of surgery until the date of first recurrence or death. OS was calculated from the day of surgery until the date of death by any cause. Patients who were lost to follow-up were censored at the date when they were last known to be alive. Kaplan-Meier analysis was done to calculate survival curves and median survival times for DFS and OS. The log rank test was used to determine if there were significant differences between survival curves. Cox proportional hazards regression was used to identify factors predictive of the 2 endpoints. Multivariate analysis was done with the forward stepwise procedure, with variables that were significant on univariate analysis (P < .05) included in the multivariate model. After the initial analysis, patients were then stratified by clinical and pathologic stage, and survival analysis was repeated. All analyses were done with SAS 9.4 (SAS Institute, Cary, North Carolina).

Results

Patient Demographics

A total of 514 patients met inclusion criteria. Demographics, pathologic stage, and treatment details are noted in Table 1 . Among the patients, 317 (61.7%) were male, and 459 (89.3%) were Caucasian. In terms of disease, 261 (50.8%) had oral tongue cancer; 398 (77.4%) underwent neck dissection; and 198 (38.5%) had nodal disease. Of the patients who did not undergo neck dissection (22.6%, 116 of 514), 84 (72.4%, 84 of 116) had stage I disease. In addition, numerous patients had primary squamous cell carcinoma of the hard palate and maxillary alveolus and were clinically observed and did not undergo neck dissection. Several others were recommended to undergo neck dissection but did not due to patient preference. Regarding the clinical care signature defined by Graboyes et al,¹⁰ 361 of 398 patients (90.7%) had a lymph node dissection with ≥18 nodes; 238 of 269 patients (88.5%) with stage III and IV disease were referred to radiation oncology; 32 (6.2%) underwent unplanned surgery within 14 days of the index surgery; and 25 (4.9%) had an unplanned readmission within 30 days of the index surgery. In total, 179 (34.8%) had disease recurrence, and 192 (37.4%) died by the end of data accrual.

Table 1.

Patient Characteristics and Adherence to Quality Metrics.^a

Characteristic	n	%
Race
Caucasian	459	89.3
Not Caucasian	55	10.7
Sex
Male	317	61.7
Female	197	38.3
Smoking status
Current	151	29.4
Former	227	44.2
Never	136	26.5
History of alcohol abuse	146	28.4
Immunocompromised	23	4.5
Oral cavity subsite
Tongue	261	50.8
Floor of mouth	89	17.3
Buccal	42	8.2
Alveolar ridge/gingiva	84	16.3
Retromolar trigone	28	5.4
Palate	7	1.3
Lip	3	0.6
Documented clinical stage
I	145	28.2
II	134	26.1
III	71	13.8
IV	163	31.7
Surgery within 21 d of initial evaluation	244	47.5
Elective neck dissection	398	77.4
Nodal disease	198	38.5
Lymph node dissection with ≥18 nodes (n = 398)	361	90.7
Intraoperative margin status
Negative	448	87.2
Positive	60	11.7
Unknown	6	1.2
Lymphovascular invasion
Yes	132	25.7
No	320	62.3
Unknown	62	12.1
Perineural invasion
Yes	164	31.9
No	289	56.2
Unknown	61	11.9
Extracapsular extension (n = 205)
Yes	107	52.2
No	90	43.9
Unknown	8	3.9
Documented pathologic stage
I	153	29.8
II	89	17.3
III	70	13.6
IV	199	38.7
Unknown	3	0.6
Unplanned surgery within 14 d	32	6.2
Unplanned readmission within 30 d	25	4.9
Referral to radiation therapy if stage III or IV disease (n = 269)	238	88.5
Start of adjuvant treatment within 6 wk of surgery (n = 273)
Yes	93	34.1
No	147	53.8
Unknown	33	12.1
Thyroid function testing within 12 mo of radiation (n = 259)
Yes	120	46.3
No	125	48.3
Unknown	14	5.4
Surveillance imaging within 6 mo of completing treatment
Yes	313	60.9
No	189	36.8
Unknown	12	2.3
Multidisciplinary follow-up (n = 269)
Yes	217	80.7
No	28	10.4
Unknown	24	8.9
Disease recurrence	179	34.8
Death	192	37.4

Bold indicates the four key quality metrics associated with improved survival in previous studies.

Survival Analysis

Median recurrence-free survival time was 9.9 years. On univariate analysis, adherence to each quality metric that was part of the clinical care signature was not associated with DFS. The only quality metric associated with increased DFS was surveillance imaging within 6 months of surgery (hazard ratio [HR] = 0.69; 95% CI, 0.5-0.96; P = .02; Table 2 ). More severe pathologic characteristics—higher tumor stage, higher nodal stage, and extracapsular extension (ECE)—were associated with decreased DFS. On multivariate analysis, no quality metrics were associated with decreased DFS; only higher tumor stage and ECE were associated. The decision was made not to look at the association between the collective clinical care signature and DFS, as no individual quality metric was associated with survival on multivariate analysis.

Table 2.

Univariate and Multivariate Analysis of Quality Metrics and Disease-Free Survival.

Quality Metric	Hazard Ratio (95% CI)	P Value^a
Univariate analysis
Surgery within 21 d of initial evaluation (no vs yes)	0.99 (0.74-1.32)	.93
Neck dissection with ≥18 nodes (no vs yes)	0.98 (0.71-1.34)	.90
Unplanned surgery within 14 d (no vs yes)	1.02 (0.52-1.99)	.96
Unplanned readmission within 30 d (no vs yes)	0.68 (0.35-1.27)	.22
Referral to radiation therapy if stage III or IV disease (no vs yes)	1.02 (0.56-1.85)	.96
Start of adjuvant treatment within 6 wk of surgery (no vs yes)	1.33 (0.87-2.05)	.19
Thyroid function testing within 12 mo of radiation (no vs yes)	0.93 (0.62-1.41)	.74
Surveillance imaging within 6 mo of treatment (yes vs no)	0.69 (0.50-0.96)	.02
Multidisciplinary follow-up (no vs yes)	0.99 (0.51-1.91)	.96
Pathologic T stage
T2 vs T1	1.18 (0.81-1.72)	.39
T3 vs T1	1.31 (0.74-2.33)	.35
T4 vs T1	2.08 (1.43-3.03)	.0001
Pathologic N stage
N1N2a vs N0	1.81 (1.14-2.87)	.01
N2b vs N0	2.34 (1.60-3.41)	<.0001
N2cN3 vs N0	2.13 (1.14-3.98)	.02
Margins (negative vs positive)	0.72 (0.48-1.09)	.12
Extracapsular extension (no vs yes)	0.39 (0.28-0.54)	<.0001
Multivariate analysis
Surveillance imaging within 6 mo of treatment (no vs yes)	0.95 (0.63-1.43)	.82
Pathologic T4 vs T1	2.09 (1.33-3.30)	.001
Pathologic N stage
N1N2a vs N0	1.37 (0.81-2.33)	.24
N2b vs N0	1.41 (0.81-2.43)	.22
N2cN3 vs N0	1.12 (0.49-2.55)	.79
Extracapsular extension (yes vs no)	0.48 (0.29-0.79)	.004

All those metrics that are significantly associated with disease-free survival are bolded (P < .05).

When stratified by clinical stage, no quality metrics were significantly associated with DFS on univariate analysis for patients with clinical stage I or II disease. For patients with clinical stage III or IV disease, unplanned readmission within 30 days was associated with decreased survival (HR = 0.45; 95% CI, 0.21-0.93; P = .03). ECE was also associated with decreased DFS ( Table 3 ). On multivariate analysis, unplanned readmission within 30 days was again associated with decreased survival (HR = 0.40; 95% CI, 0.20-0.85; P = .02), as was ECE. When stratified by pathologic stage, neck dissection with <18 nodes was associated with decreased survival for those patients with pathologic stage I or II disease (HR = 2.04; 95% CI, 1.23-3.36; P = .005). For pathologic stage III or IV disease, no quality metrics were associated with decreased survival, although ECE was.

Table 3.

Univariate and Multivariate Analysis of Quality Metrics and Disease-Free Survival Stratified by Clinical and Pathologic Stage.

Quality Metric	Hazard Ratio (95% CI)	P Value^a	Hazard Ratio (95% CI)	P Value^a
Univariate analysis
	Clinical stage I and II		Pathologic state I and II
Surgery within 21 d of initial evaluation (no vs yes)	0.86 (0.56-1.32)	.50	0.76 (0.48-1.23)	.28
Neck dissection with ≥18 nodes (no vs yes)	1.36 (0.89-2.08)	.16	2.04 (1.23-3.36)	.005
Unplanned surgery within 14 d (no vs yes)	0.60 (0.19-1.92)	.39	0.98 (0.14-7.09)	.98
Unplanned readmission within 30 d (no vs yes)	1.76 (0.43-7.16)	.43	1.31 (0.32-5.36)	.71
Start of adjuvant treatment within 6 wk of surgery (no vs yes)	1.22 (0.51-2.90)	.66	0.67 (0.14-3.25)	.62
Thyroid function testing within 12 mo of radiation (no vs yes)	0.73 (0.32-1.67)	.46	1.44 (0.35-5.87)	.61
Surveillance imaging within 6 mo of treatment (yes vs no)	0.68 (0.44-1.06)	.09	0.76 (0.48-1.23)	.27
Multidisciplinary follow-up (no vs yes)	0.47 (0.13-1.62)	.23	1.07 (0.29-3.94)	.92
Margins (negative vs positive)	0.56 (0.31-1.01)	.06	0.74 (0.37-1.50)	.41
	Clinical stage III and IV		Pathologic state III and IV
Surgery within 21 d of initial evaluation (no vs yes)	0.98 (0.65-1.47)	.91	1.07 (0.73-1.56)	.74
Neck dissection with ≥18 nodes (no vs yes)	0.93 (0.49-1.74)	.81	0.70 (0.36-1.40)	.31
Unplanned surgery within 14 d (no vs yes)	1.45 (0.63-3.32)	.38	1.22 (0.60-2.52)	.58
Unplanned readmission within 30 d (no vs yes)	0.45 (0.22-0.93)	.03	0.58 (0.28-1.20)	.14
Referral to radiation therapy if stage III or IV disease (no vs yes)	0.69 (0.32-1.51)	.36	1.02 (0.56-1.85)	.96
Start of adjuvant treatment within 6 wk of surgery (no vs yes)	1.45 (0.88-2.40)	.15	1.54 (0.97-2.45)	.06
Thyroid function testing within 12 mo of radiation (no vs yes)	1.05 (0.65-1.70)	.84	0.92 (0.59-1.42)	.70
Surveillance imaging within 6 mo of treatment (yes vs no)	0.80 (0.49-1.30)	.37	0.89 (0.55-1.45)	.64
Multidisciplinary follow-up (no vs yes)	1.78 (0.81-3.88)	.15	1.24 (0.54-2.86)	.61
Margins (negative vs positive)	0.92 (0.52-1.62)	.77	0.76 (0.45-1.28)	.31
Extracapsular extension (no vs yes)	0.39 (0.26-0.59)	<.0001	0.45 (0.31-0.67)	<.0001
Multivariate analysis for clinical stage III and IV
Unplanned readmission within 30 d (no vs yes)	0.40 (0.19-0.85)	.02
Extracapsular extension (no vs yes)	0.41 (0.23-0.74)	.003

All those metrics that are significantly associated with disease-free survival are bolded (P < .05).

Regarding OS, median survival time from death of all causes was 11.1 years. Of the 4 key quality metrics in the clinical care signature, neck dissection with ≤18 nodes (HR = 0.62; 95% CI, 0.44-0.86; P = .004) and unplanned surgery within 14 days were associated with decreased survival (HR = 0.56; 95% CI, 0.32-0.96; P = .03; Table 4 ). More aggressive pathologic characteristics—higher tumor stage, higher nodal stage, and ECE—were also associated with decreased OS. On multivariate analysis, no quality metrics were associated with OS; only higher tumor stage, higher nodal stage, and ECE were associated with decreased OS.

Table 4.

Univariate and Multivariate Analysis of Quality Metrics and Overall Survival.

Quality Metric	Hazard Ratio (95% CI)	P Value^a
Univariate analysis
Surgery within 21 d of initial evaluation (no vs yes)	1.16 (0.87-1.54)	.30
Neck dissection with ≥18 nodes (no vs yes)	0.62 (0.44-0.86)	.002
Unplanned surgery within 14 d (no vs yes)	0.56 (0.32-0.96)	.03
Unplanned readmission within 30 d (no vs yes)	0.76 (0.39-1.48)	.42
Referral to radiation therapy if stage III or IV disease (no vs yes)	0.9 (0.53-1.52)	.69
Start of adjuvant treatment within 6 wk of surgery (no vs yes)	0.95 (0.65-1.38)	.77
Thyroid function testing within 12 mo of radiation (no vs yes)	1.18 (0.81-1.72)	.39
Surveillance imaging within 6 mo of treatment (no vs yes)	0.91 (0.68-1.23)	.54
Multidisciplinary follow-up (no vs yes)	0.96 (0.54-1.67)	.88
Pathologic T stage
T2 vs T1	1.99 (1.36-2.91)	.0004
T3 vs T1	2.38 (1.39-4.09)	.002
T4 vs T1	3.53 (2.39-5.19)	<.0001
Pathologic N stage
N1N2a vs N0	2.65 (1.74-4.05)	<.0001
N2b vs N0	3.27 (2.26-4.73)	<.0001
N2cN3 vs N0	3.28 (1.82-5.91)	<.0001
Margins (negative vs positive)	0.90 (0.60-1.37)	.63
Extracapsular extension (yes vs no)	0.28 (0.20-0.38)	<.0001
Multivariate analysis
Unplanned surgery within 14 d (no vs yes)	0.65 (0.37-1.15)	.14
Pathologic T stage
T2 vs T1	1.46 (0.92-2.33)	.11
T3 vs T1	1.57 (0.84-2.93)	.16
T4 vs T1	2.78 (1.75-4.42)	<.0001
Pathologic N stage
N1N2a vs N0	1.73 (1.06-2.80)	.03
N2b vs N0	1.69 (1.04-2.73)	.03
N2cN3 vs N0	1.918 (0.93-3.96)	.08
Extracapsular extension (yes vs no)	0.46 (0.30-0.71)	.001

All those metrics that are significantly associated with overall survival are bolded (P < .05).

Discussion

Quality metrics for this study were chosen on the basis of previous studies, American Head and Neck Society guidelines, and National Comprehensive Cancer Network guidelines ( Table 1 ).^9,10 Adherence to the quality metrics examined in this study was mixed. For example, adherence to the clinical care signature defined by Graboyes et al was high and comparable to previously reported rates.¹⁰ However, 52.5% of patients did not undergo surgery within 21 days of their initial assessment, and only 34.1% who underwent radiation did so within 6 weeks of their index surgery. These rates are also comparable to those reported in the literature,^10-12 suggesting that across institutions, improved compliance with these suggested measures should be targeted. Unfortunately, while adherence to some quality metrics evaluated in other studies—such as tobacco cessation counseling, dental evaluation, and human papilloma virus status—could not be ascertained in our patient population (as this information was not recorded in many patient charts), a concerted effort has since been made to better document these metrics.

In this study, more aggressive pathologic characteristics, rather than adherence to process-related quality metrics, were consistently associated with decreased DFS and OS among patients with OCSCC who underwent primary surgical therapy. For example, regardless of clinical or pathologic stage, ECE was associated with decreased DFS and OS on all analyses. In an effort to mitigate potential confounding by severity of disease, patients were then stratified by clinical and pathologic stages; despite this, quality metrics were not associated with improved survival, differing from what was reported in previous studies.^8,10,13,14 Nevertheless, adherence to some quality metrics were associated with improved survival on univariate analysis in this study and may warrant further examination.

When all patients in this study were examined, the only quality metric associated with DFS on univariate analysis was surveillance imaging within 6 months of surgery. As early detection of recurrence at a lower stage is assumed to correlate with improved survival, typical practice for head and neck cancer includes imaging with positron emission tomography–computed tomography of the neck within 6 months of treatment, per the National Comprehensive Cancer Network guidelines.^15-17 Thus, it stands to reason that adherence to early surveillance would be associated with increased DFS. This association, however, was not seen on multivariate analysis, suggesting that more investigation is required to determine if this quality metric has strong clinical significance.

When stratified by disease stage, an unplanned readmission within 30 days of the index surgery was associated with decreased DFS on univariate and multivariate analysis for those patients with clinical stage III or IV disease. This quality metric was the only 1 of the 4 key quality metrics associated with DFS in the Graboyes et al study.¹⁰ Following head and neck surgery, unplanned readmissions are usually the result of cardiac or respiratory comorbidities, surgical site infections, or difficulty with transitions of care.^18,19 In our cohort, similar reasons for readmission were seen, including postoperative pneumonia, concerns regarding care of the patient at a skilled nursing facility, and wound breakdown. Given that higher-stage disease is often treated with more extensive surgery, such as a free tissue transfer with microvascular anastomosis, it stands to reason that to prevent readmissions, early mobilization of the patient and detailed communication regarding postoperative care during transitions of care are paramount.^18,20 Furthermore, this is a metric often evaluated by the Centers for Medicare and Medicaid Services in determining hospital reimbursement; thus, this finding underscores the importance of attempting to reduce readmissions. However, it is not clear why readmissions are associated with DFS, and this relationship requires further investigation to improve care for these patients.

Two of the metrics in the clinical care signature described by Graboyes et al—unplanned surgery within 14 days and lymph node dissection with yield ≥18 nodes—were associated with OS on univariate analysis. In our cohort, unplanned surgery within 14 days of the index surgery was usually due to exploration of the postoperative neck for free flap compromise or hematoma. Underlying patient comorbidities, especially cardiovascular conditions, predispose patients to these postoperative complications.²¹ Previously published data at our institution did support this association as well.²² The potential link among postoperative complications, patient comorbidities, and OS warrants further investigation. Overall, careful multidisciplinary preoperative evaluation and postoperative management for patients with significant medical comorbidities are likely necessary in improving adherence to this quality metric.

In addition to being associated with improved OS on univariate analysis, neck dissection with yield ≥18 nodes was associated with improved DFS with pathologic stage I or II disease in our cohort. Lymph node dissection with yield ≥18 nodes was shown in multiple studies to be associated with improved survival.^13,18,23-26 Thus, even though the association between this quality metric and OS was not maintained on multivariate analysis, this is likely an important quality metric for patients with OCSCC who are treated with primary surgery. As a complete, thorough neck dissection is associated with lower rates of locoregional recurrence and OS²⁶ and identification of positive lymph node disease leads to adjuvant treatment, it stands to reason that this quality metric is associated with an advantage in survival seen for these patients. Thus, this is a metric for which the head and neck surgeon should strive for high compliance.

The association between the clinical care signature with DFS and OS seen in the Graboyes et al study were not consistently seen in our cohort.¹⁰ However, there are many limitations to our study. First, this was a retrospective study dating back to 1995. Practices and level of focus on many of the quality metrics examined have likely changed over this period. Additionally, given the retrospective nature, data accrual was limited by the accuracy of the medical record. There were many gaps in our electronic medical record given the lack of standardization in documentation, and this has been seen at other institutions as well.²⁷ Moving forward, a standardized protocol for documentation with a special focus on proposed quality metrics would greatly help future investigations, and a concerted effort has been made to do so at our institution. This study was limited to a single institution, thus limiting its generalizability. Specifically, since our institution is a tertiary care academic center, baseline compliance with quality metrics is likely higher than in the general community due to greater resources and infrastructure. Moreover, given the overall high level of favorable oncologic outcomes seen in our cohort, analyses determining predictors of survival outcomes are possibly underpowered. Thus, a prospective multi-institutional study with multiple surgeons is likely necessary to further determine process-related quality metrics that have clinical significance for patients with OCSCC.

Conclusions

In this study, among patients with stage III and IV OCSCC treated with definitive surgery, only unplanned readmission within 30 days of the index surgery was associated with decreased DFS on multivariate analysis. These results differ from similar studies performed at other tertiary care centers. Thus, although there has been a call for nationally endorsed process-related quality metrics in head and neck cancer surgery, further investigation is necessary to elucidate those that have a meaningful impact on patient survival.

Author Contributions

Swathi Appachi, acquisition, analysis and interpretation of data, drafting and revision of manuscript, approval of version to be published, agreement to be accountable for all aspects; Janki Shah, acquisition and analysis of data, revision of manuscript, approval of version to be published, agreement to be accountable for all aspects; Chandana Reddy, analysis and interpretation of the data, drafting of manuscript, approval of the manuscript, agreement to be accountable for all aspects; Andrew Bowen, acquisition and analysis of data, revision of manuscript, approval of version to be published, agreement to be accountable for all aspects; Shlomo Koyfman, interpretation of the data, drafting of the manuscript, approval of the manuscript, agreement to be accountable for all aspects; Eric Lamarre, interpretation of the data, revision and approval of the manuscript, agreement to be accountable for all aspects

Disclosures

Competing interests: Shlomo Koyfman, Merck—research funding; Varian—educational consultant.

Sponsorships: None.

Funding source: None.

Footnotes

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

This article was presented at the AAO-HNSF 2018 Annual Meeting & OTO Experience; October 7-10, 2018; Atlanta, Georgia.

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