Abstract
Purpose:
Salvage surgical treatment of oropharyngeal cancer is associated with significant morbidity. We aim to identify predictive factors of functional outcomes to improve patient selection and counseling when contemplating salvage oropharyngectomy.
Methods:
Patients with a history of radiation requiring salvage oropharyngeal surgery were identified. Primary outcomes were determined at one year post-salvage surgery and included Gastric tube (G-tube) dependence, dietary restrictions, tracheostomy dependence, and speech intelligibility. Multivariate analyses were performed to identify predictors of the primary outcomes.
Results:
At one year, 45% (22/49) of patients had a G-tube, 68% (33/48) had dietary restrictions, 10% (5/49) remained tracheostomy dependent, and 15% (4/26) had difficulty with speech intelligibility. On univariate analysis, pre-operative G-tube (83% vs. 40%, p=0.04), reconstruction with a free flap (54% vs. 0%, p=0.005), and bony resection (69% vs. 36%, p=0.04) were significantly associated with G-tube dependence at one year. On multivariate analysis, concurrent bony resection remained a significant predictor of G-tube dependence (HR 5.4, 95% CI 1.2–24, p=0.03). Predictors of dietary restriction included free-flap reconstruction (78% vs. 25%, HR 0.13, 95% CI 0.02–0.87, p=0.04) and recurrence after two years (85% vs. 48%, HR 4.9, 95% CI 1.2–21, p=0.03). Supraglottic laryngectomy was significantly associated with tracheostomy dependence on univariate (67% vs. 7%, p=0.001) and multivariate analysis (HR 44.4, 95% CI 2.0–986, p=0.02).
Conclusion and Relevance:
Functional outcomes are suboptimal after salvage oropharyngectomy. Specific patient and disease factors are independently associated with worse speech and swallowing outcomes and may aid in pre-operative patient selection, risk stratification, and shared decision-making.
Keywords: Functional outcomes, oropharynx, salvage surgery, tracheostomy dependence
Introduction
Oropharyngeal squamous cell carcinoma (OPSCC) is the most common cancer of the head and neck reflecting the increase in incidence of HPV-mediated disease [1, 2]. In this younger population which experiences improved survival, there has been a shift towards treatment paradigms that limit long-term toxicity and functional consequences [3–10]. As such, there is a growing population of survivors who have been treated with primary radiation-based protocols.
Despite the improved survival in HPV-positive disease, up to a third of these patients will ultimately develop recurrent/persistent or second-primary disease [11–14]. In the setting of recurrent head and neck cancer after primary RT or CRT, salvage surgery is the predominant treatment. Unfortunately, prognosis for recurrent disease is poor and treatment engenders significant morbidity [15–17]. Specifically, studies focusing on speech and swallow outcomes have revealed that at best, half of patients will approach their baseline functional status [16–18]. To improve pre-treatment patient counseling and ultimately patient selection, studies have investigated factors associated with worse functional outcomes, however the majority of these are in the primary setting [19–26]. In the few studies focusing on salvage treatment, only recurrent stage and tumor site have been found to be predictive of functional outcomes [15, 16].
An improved understanding of pre-operative clinical variables associated with post-salvage functional outcomes will allow for improved patient counseling and shared decision making. Herein, we investigate a cohort of patients treated with head and neck radiation undergoing salvage surgery of the oropharynx to identify patient or disease factors associated with functional endpoints at one-year post salvage treatment.
Methods
Study Population
This study was approved by the University of Michigan Institutional Review Board (HUM00081554). Patients with a history of prior head and neck radiation who presented with persistent, recurrent or second primary disease requiring salvage surgery between 1998 and 2017 involving the oropharynx were identified (n=99). Patients who developed recurrent disease within one year of salvage surgery (n=38) and patients requiring laryngectomy (n=12) were excluded.
Demographic and disease characteristics were collected including patient age at diagnosis, sex, tobacco and alcohol use, comorbidities (diabetes, lung disease, cardiac disease, immune suppression), body mass index (BMI), HPV status (as determined by p16 expression), time to recurrence (defined as time from completion of primary RT or CRT to salvage surgery), primary and recurrent tumor site and stage (AJCC 7th edition) [27], pre-operative tracheostomy, pre-operative gastrostomy tube (G-tube), and treatment details including extent of surgical resection, bony resection, free flap reconstruction, and post-operative adjuvant radiation or chemoradiation.
Post-operative functional status at one year was collected including mode of nutrition, solid restrictions (no solids, pureed diet, soft diet, minimal limitation (i.e. bread, meat), full range of solids), and liquid restrictions (no liquids per mouth, requires thickened liquids, limits with bolus volume, full range of liquids). Primary outcomes were measured at one year post-operatively and included tracheostomy tube dependence, G-tube dependence, speech intelligibility, and dietary restrictions defined as requiring thickened liquids, soft or pureed diet, or inability to take solids or liquids by mouth.
Statistical Analysis
Univariate analysis to evaluate patient and disease characteristic associated with functional outcomes was performed using nonparametric tests (i.e. Fisher’s exact test, chi-square test with Monte Carlo estimates for error terms) and p-values less than 0.05 were considered significant. For multivariate analyses, a backward selected binary logistic regression model was performed. Clinical variables with p-values <0.1 on univariate analysis were included into the model. Statistical analysis was performed with SPSS v. 26 (IBM; Armonk, NY).
Results
Cohort Demographics
Patient and disease characteristics are described in Table 1. Patients were predominantly male (71%) with an average age of 63 years. The majority (69%) of patients received primary radiation or chemoradiation treatment for oropharyngeal disease, however a subset of patients received initial radiation for oral cavity (12%) or other primary tumors (18%) of the head and neck. The median time to recurrence was 2.7 years and 45% (22/49) of patients presented with early stage (stage I/II) recurrences, while 55% (27/49) of patients presented with advanced stage (stage III/IV) recurrences. Pre-operatively, only one patient was tracheostomy dependent, while six patients had pre-operative G-tubes.
Table 1.
Correlation of mRNA expression levels of six candidate genes in chr11p15.5 region and asthma-related phenotypes in bronchial epithelial cells in SARP.
| Variable |
Trach at 1yr n (%) |
Speech Understandability n (%) |
G-tube at 1 yr n (%) |
Dietary Restrictions n (%) |
|||||
|---|---|---|---|---|---|---|---|---|---|
| No | Yes | No/Mild Difficulty | Significant Difficulty | No | Yes | No | Yes | ||
| Sex | Male | 31 (89) | 4 (11) | 17 (85) | 3 (15) | 19 (54) | 16 (46) | 10 (29) | 25 (71) |
| Female | 13 (93) | 1 (7) | 5 (83) | 1 (17) | 8 (57) | 6 (43) | 5 (38) | 8 (62) | |
| Initial Site | Oral Cavity | 6 (100) | 0 (0) | 2 (100) | 0 (0) | 4 (67) | 2 (33) | 4 (67) | 2 (33) |
| Oropharynx | 29 (85) | 5 (15) | 18 (86) | 3 (14) | 17 (50) | 17 (50) | 9 (27) | 24 (73) | |
| Other | 9 (100) | 0 (0) | 2 (67( | 1 (33) | 6 (67) | 3 (13) | 2 (22) | 7 (78) | |
| Initial Overall Stage | Early Stage (I/II) | 8 (100) | 0 (0) | 4 (100) | 0 (0) | 4 (50) | 4 (50) | 3 (43) | 4 (57) |
| Advanced Stage (III/IV) | 29 (88) | 4 (12) | 15 (88) | 2 (12) | 19 (58) | 14 (42) | 10 (30) | 23 (70) | |
| Recurrent Overall Stage | Early (I/II) | 20 (90) | 2 (10) | 8 (89) | 1 (11) | 14 (64) | 8 (36) | 10 (48) | 11 (52) |
| Advanced (III/IV) | 24 (88) | 3 (12) | 14 (82) | 3 (18) | 13 (48) | 14 (52) | 5 (19) | 22 (81) | |
| Recurrent T Stage | Early (T1/2) | 23 (88) | 3 (12) | 10 (91) | 1 (9) | 17 (65) | 9 (35) | 12 (48) | 13 (52) |
| Advanced (T3/4) | 21 (91) | 2 (9) | 12 (80) | 3 (20) | 10 (43) | 13 (57) | 3 (13) | 20 (87) | |
| Recurrent cN Stage | cN0 | 35 (92) | 3 (8) | 16 (84) | 3 (16) | 19 (50) | 19 (50) | 11 (30) | 26 (70) |
| cN+ | 9 (82) | 2 (18) | 6 (86) | 1 (14) | 8 (73) | 3 (27) | 4 (36) | 7 (64) | |
| Recurrent Adjuvant RT | No | 38 (90) | 4 (10) | 18 (82) | 4 (18) | 25 (60) | 17 (40) | 14 (34) | 27 (66) |
| Yes | 6 (86) | 1 (14) | 4 (100) | 0 (0) | 2 (29) | 5 (71) | 1 (14) | 6 (86) | |
| Time to Recurrence | ≤ 2 yr | 20 (91) | 2 (9) | 9 (82) | 2 (18) | 15 (68) | 7 (32) | 11 (52) | 10 (48) |
| > 2 yr | 24 (89) | 3 (11) | 13 (87) | 2 (13) | 12 (44) | 15 (56) | 4 (15) | 23 (85) | |
| HPV Status | Negative | 11 (92) | 1 (8) | 5 (71) | 2 (29) | 6 (50) | 6 (50) | 3 (25) | 9 (75) |
| Positive | 8 (73) | 3 (27) | 5 (83) | 1 (17) | 5 (45) | 6 (55) | 4 (36) | 7 (64) | |
| Tobacco Use | Never | 9 (90) | 1 (10) | 3 (60) | 2 (40) | 6 (60) | 4 (40) | 5 (50) | 5 (50) |
| Former/Current | 34 (90) | 4 (10) | 19 (90) | 2 (10) | 21 (54) | 18 (46) | 10 (26) | 28 (74) | |
| BMI | ≤ 20 | 37 (88) | 5 (12) | 21 (84) | 4 (16) | 24 (57) | 18 (43) | 14 (33) | 28 (67) |
| > 20 | 4 (100) | 0 (0) | 1 (100) | 0 (0) | 2 (50) | 2 (50) | 0 (0) | 3 (100) | |
| Diabetes Mellitus | No | 42 (89) | 5 (11) | 21 (84) | 4 (16) | 25 (53) | 22 (47) | 13 (28) | 33 (72) |
| Yes | 2 (100) | 0 (0) | 1 (100) | 0 (0) | 2 (100) | 0 (0) | 2 (100) | 0 (0) | |
| Pre-Operative Trach | No | 43 (90) | 5 (10) | 22 (88) | 3 (12) | 27 (56) | 21 (44) | 15 (32) | 32 (68) |
| Yes | 1 (100) | 0 (0) | 0 (0) | 1 (100) | 0 (0) | 1 (100) | 0 (0) | 1 (1) | |
| Pre-Operative G-Tube | No | 38 (88) | 5 (12) | 21 (87.5) | 3 (12.5) | 26 (60) | 17 (40) | 14 (33) | 28 (67) |
| Yes | 6 (100) | 0 (0) | 1 (50) | 1 (50) | 1 (17) | 5 (83) | 1 (17) | 5 (83) | |
| Resection Sites | Oropharynx Only | 20 (95) | 1 (5) | 11 (85) | 2 (15) | 13 (62) | 8 (38) | 5 (25) | 15 (75) |
| Includes Oral Cavity | 23 (92) | 2 (8) | 10 (91) | 1 (9) | 13 (52) | 12 (48) | 10 (40) | 15 (60) | |
| Includes Supraglottis | 1 (33) | 2 (67) | 1 (50) | 1 (50) | 1 (33) | 2 (67) | 0 (0) | 3 (100) | |
| Bony Resection | No | 34 (94) | 2 (6) | 15 (79) | 4 (21) | 23 (64) | 13 (36) | 11 (31) | 25 (69) |
| Yes | 10 (77) | 3 (23) | 7 (100) | 0 (0) | 4 (31) | 9 (69) | 4 (33) | 8 (67) | |
| Free Flap Reconstruction | No | 8 (100) | 0 (0) | 4 (100) | 0 (0) | 8 (100) | 0 (0) | 6 (75) | 2 (25) |
| Yes | 36 (87) | 5 (13) | 18 (82) | 4 (18) | 19 (46) | 22 (54) | 9 (22.5) | 31 (77.5) | |
The extent of resection involved the oropharynx alone in 43% (21/49), the oropharynx with extension into the oral cavity in 53% (26/49), and the oropharynx with extension to the supraglottis in 6% (3/49) of patients. Twenty-seven percent (13/49) of patients required bony resection and 84% (41/49) underwent free flap reconstruction. Four patients (8%) underwent adjuvant radiation and three patients (6%) underwent chemoradiation after salvage surgery.
Functional Outcomes
At one-year post-salvage surgery, 10% (5/49) of patients had a tracheostomy while 45% (22/49) of patients remained at least partially G-tube dependent (Table 2). With regard to nutritional mode at one year, only 4% (2/49) of patients were NPO, while 41% (20/49) of patients maintained a combination of oral and G-tube feeding. Fifty-five percent of patients maintained an oral diet with no or minimal nutritional supplementation. Upon investigation of dietary restrictions, we found that solid restrictions were more common than liquid restrictions. Only 30% (14/47) of patients were able to eat a full range or solids or had minimal restrictions (i.e. bread, meat), while 34% (16/47) of patients required a soft diet, 13% (6/47) required a pureed diet, and 23% (11/47) of patients were unable to take any solids per mouth. In contrast 70% (31/45) of patients were able to take a full range of liquids, while 9% (4/45) required thickeners, and 18% (8/45) were unable to take any liquids per mouth. Finally, with regard to speech outcomes, the majority of patients (62%) had minimal to no difficulty with speech understanding, while 23% of patients required face to face communication, and only 15% of patients had significant difficulty with speech understanding. No patients required written communication.
Table 2.
Functional Outcomes
| Outcome Measured | % (n) | |
|---|---|---|
| Tracheostomy Dependence (1 yr) | 10% (5/49) | |
| Gastrostomy Tube Dependence (1 yr) | 45% (22/49) | |
| Dietary Restrictions (Solids) | No solids | 23% (11/47) |
| Pureed | 13% (6/47) | |
| Minced, moist, soft diet | 34% (16/47) | |
| Limitations with some consistencies (i.e. bread, meat) | 17% (8/47) | |
| Full range of solids | 13% (6/47) | |
| Dietary Restrictions (Liquids) | Limited to no liquids per mouth | 18% (8/45) |
| Restricted consistency (i.e. requires thickener) | 9% (4/45) | |
| Limits with bolus volume (full range of liquids) | 4% (2/45) | |
| Full range of liquids | 70% (31/45) | |
| Nutritional Mode | Nil Per Os | 4% (2/49) |
| Combined oral and G-tube nutrition | 41% (20/49) | |
| Requires dietary supplements (All oral nutrition) | 18% (9/49) | |
| Normal Diet | 37% (18/49) | |
| Speech Understandability | Never Understandable, Requires written communication | 0% (0/26) |
| Difficult to Understand | 15% (4/26) | |
| Usually Understandable (requires face to face communication) | 23% (6/26) | |
| Understandable most or all of the time with minimal repeating | 62% (16/26) | |
Predictors of Post-Operative Tracheostomy, G-tube, Dietary Restrictions, and Speech Outcomes
Univariate and multivariate analyses were subsequently performed to identify clinical predictors of tracheostomy or G-tube dependence, dietary restriction, and speech intelligibility at one year (Figure 1). On univariate analysis supraglottic resection (67% vs. 7%, p=0.001) was significantly associated with tracheostomy dependence at one year. On multivariate analysis, supraglottic resection remained a significant predictor of tracheostomy dependence (HR 44.4, 95% CI 2.0–986, p=0.02) (Figure 2a). Significant predictors of G-tube dependence at one year included pre-operative G-tube (83% vs. 40%, p=0.04), bony resection (69% vs. 36%, p=0.04), and reconstruction with free tissue (54% vs. 0%, p=0.005). On multivariate analysis bony resection was the only significant predictor of G-tube dependence, with patients undergoing bony resection having a significantly higher risk of G-tube at one year compared to those not requiring bony resection (HR 5.5, 95% CI 1.2–24, p=0.03) (Figure 2b). Further, univariate analysis identified recurrent T-stage (87% vs. 52%, p=0.009), time to recurrence greater than 2 years (85% vs. 48%, p=0.005), diabetes mellitus (0% vs. 72%, p=0.03), and reconstruction with a free flap (78% vs. 25%, p=0.003) to be significantly associated with dietary restrictions at one year. On multivariate analysis, reconstruction requiring a free flap (HR 7.5, 95% CI 1.1–48, p=0.04), and recurrence after two years continued to be predictive of worse dietary range (HR 4.9, 95% CI 1.2–21, p=0.03) (Figure 2c). For speech intelligibility, pre-operative trach was a significant predictor on univariate analysis (100% vs 12%, p=0.02), however was not significantly predictive of speech outcomes on multivariate analysis. We found no significant association between patient age, sex, tobacco use, alcohol use, BMI, HPV status, immune suppression, use of adjuvant radiation after salvage surgery, or recurrent tumor site with our primary outcomes.
Figure 1: Predictors of Functional Outcomes One-Year After Salvage Surgery.
Chi-Squared analysis was used to identify significant predictors of tracheostomy dependence, G-tube dependence, dietary restrictions, and speech intelligibility. p-values < 0.05 were considered significant. The x-axis lists the clinical variables and y-axis represents percent of patients in each group.
Figure 2: Multivariate Analysis of Predictors of Functional Outcomes.
Variables with p-values < 0.1 were included into the backward selection multivariate model. Variables included in the final model are depicted above. Significance was taken at a p-value < 0.5 and is indicated with an asterisk. (A) Tracheostomy dependence, controlling for supraglottic resection and bony resection. (B) G-tube dependence, controlling for pre-operative G-tube, bony resection, time to recurrence, and use of free flap reconstruction. (C) Dietary restriction, controlling for recurrent T stage, time to recurrence, diabetes, and free flap reconstruction.
Discussion
Here we demonstrate that multiple pre-salvage patient and disease variables are predictive of tracheostomy dependence, G-tube dependence, and dietary restrictions one year after salvage surgery. In contrast to previous studies which have demonstrated that recurrent stage predicts worse dysphagia and speech intelligibility scores [15, 16], our data demonstrate that when controlling for additional clinical factors such as comorbidities, time to recurrence, and use of free flap reconstruction, stage was not a significant predictor of dietary restriction or speech intelligibility. Our results also suggest that patients who do not require free tissue reconstruction have improved dietary outcomes likely reflecting the smaller and less extensive resections in this group. Finally, a longer time between primary treatment and salvage surgery was predictive of worse dietary restrictions which may be a function of increased stage due to later diagnosis, or may be reflective of late onset toxicities of primary radiation therapy [24, 26].
In a population already predisposed to depression and social isolation[20, 28, 29], salvage treatment incurs additional risks to patient’s quality of life. Due to often extensive surgeries and resulting speech and swallow morbidity, salvage treatment may lead to further social isolation due to effects on communication and ability to eat in public. Therefore, a focus on not only survival but quality of life outcomes becomes increasingly important in this population. In an era emphasizing shared decision making, head and neck surgeons have the responsibility to understand the variables that may give insight into realistic challenges for post-salvage quality of life [30, 31]. We provide evidence for pre-operative factors that may predispose to worse speech and swallow outcomes to aid with pre-operative discussions. It is also critical to realize that patients may have different priorities and expectations which may engender varying reflections on their treatment choice and ultimate recovery [32, 33]. These concepts and discussions are obligatory to preoperative discussions.
These results complement previously published data identifying clinical variables associated with survival in this cohort [34]. Together these data can improve selection from both a survival and quality of life standpoint. In patients with pre-operative status that predicts poor survival or functional outcomes, or for patients unwilling to accept a higher likelihood of these endpoints, alternative therapies such as immunotherapy or ongoing clinical trials might be considered.
Limitations of this study include a relatively small sample size and heterogenous population. However, given the primary outcomes of this study were functional in nature, we felt that inclusion of multiple tumor sites tumors that resulted in at least partial oropharyngeal resection would provide valuable insight into post-salvage functional outcomes. The lack of a validated and consistent set of patient-reported functional outcomes is a significant shortfall, however our reliance on objective cutoffs mitigates variability in measurement/reporting. Speech intelligibility data was only available in 26/49 patients which limited the analysis of this outcome and may explain the lack of significant predictive variables in this study. Further pre-operative radiation dosing and fields were not available and may significantly influence functional outcomes.
Overall these data provide insight into predictive factors that may help with pre-operative counseling of a vulnerable population and additional studies are warranted to further investigate these findings.
Acknowledgments:
M.E.H received funding from NIH grant T32 DC005356. J.C.B. received funding from NIH Grants P30-CA046592 and the American Cancer Society. Funding sources had no role in study design, collection/analysis/interpretation of data, writing of decision for submission of this article.
Footnotes
Conflicts of interest/Competing interests: The authors have no conflicts of interest to declare.
Code availability: Not applicable
Availability of data and material:
Data available upon request
References:
- 1.Bray F, et al. , Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018. 68(6): p. 394–424. [DOI] [PubMed] [Google Scholar]
- 2.Chaturvedi AK, et al. , Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol, 2011. 29(32): p. 4294–301. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Calais G, et al. , Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma. J Natl Cancer Inst, 1999. 91(24): p. 2081–6. [DOI] [PubMed] [Google Scholar]
- 4.Denis F, et al. , Final results of the 94–01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol, 2004. 22(1): p. 69–76. [DOI] [PubMed] [Google Scholar]
- 5.Haughey BH and Sinha P, Prognostic factors and survival unique to surgically treated p16+ oropharyngeal cancer. Laryngoscope, 2012. 122 Suppl 2: p. S13–33. [DOI] [PubMed] [Google Scholar]
- 6.Huang K, et al. , Intensity-modulated chemoradiation for treatment of stage III and IV oropharyngeal carcinoma: the University of California-San Francisco experience. Cancer, 2008. 113(3): p. 497–507. [DOI] [PubMed] [Google Scholar]
- 7.Worden FP, et al. , Chemoselection as a strategy for organ preservation in advanced oropharynx cancer: response and survival positively associated with HPV16 copy number. J Clin Oncol, 2008. 26(19): p. 3138–46. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Monnier Y and Simon C, Surgery Versus Radiotherapy for Early Oropharyngeal Tumors: a Never-Ending Debate. Curr Treat Options Oncol, 2015. 16(9): p. 42. [DOI] [PubMed] [Google Scholar]
- 9.Nichols AC, et al. , Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomised trial. Lancet Oncol, 2019. 20(10): p. 1349–1359. [DOI] [PubMed] [Google Scholar]
- 10.O’Connell D, et al. , Primary surgery versus chemoradiotherapy for advanced oropharyngeal cancers: a longitudinal population study. J Otolaryngol Head Neck Surg, 2013. 42(1): p. 31. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Faraji F, Eisele DW, and Fakhry C, Emerging insights into recurrent and metastatic human papillomavirus-related oropharyngeal squamous cell carcinoma. Laryngoscope Investig Otolaryngol, 2017. 2(1): p. 10–18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Lassen P, et al. , Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck. J Clin Oncol, 2009. 27(12): p. 1992–8. [DOI] [PubMed] [Google Scholar]
- 13.Nguyen-Tan PF, et al. , Randomized phase III trial to test accelerated versus standard fractionation in combination with concurrent cisplatin for head and neck carcinomas in the Radiation Therapy Oncology Group 0129 trial: long-term report of efficacy and toxicity. J Clin Oncol, 2014. 32(34): p. 3858–66. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Taneja C, et al. , Changing patterns of failure of head and neck cancer. Arch Otolaryngol Head Neck Surg, 2002. 128(3): p. 324–7. [DOI] [PubMed] [Google Scholar]
- 15.Culie D, et al. , Salvage surgery for recurrent oropharyngeal cancer: post-operative oncologic and functional outcomes. Acta Otolaryngol, 2015. 135(12): p. 1323–9. [DOI] [PubMed] [Google Scholar]
- 16.Goodwin WJ Jr., Salvage surgery for patients with recurrent squamous cell carcinoma of the upper aerodigestive tract: when do the ends justify the means? Laryngoscope, 2000. 110(3 Pt 2 Suppl 93): p. 1–18. [DOI] [PubMed] [Google Scholar]
- 17.Zafereo ME, et al. , The role of salvage surgery in patients with recurrent squamous cell carcinoma of the oropharynx. Cancer, 2009. 115(24): p. 5723–33. [DOI] [PubMed] [Google Scholar]
- 18.Nichols AC, et al. , Surgical salvage of the oropharynx after failure of organ-sparing therapy. Head Neck, 2011. 33(4): p. 516–24. [DOI] [PubMed] [Google Scholar]
- 19.Agra IM, et al. , Second salvage surgery for re-recurrent oral cavity and oropharynx carcinoma. Head Neck, 2010. 32(8): p. 997–1002. [DOI] [PubMed] [Google Scholar]
- 20.Bozec A, et al. , Long-term quality of life and psycho-social outcomes after oropharyngeal cancer surgery and radial forearm free-flap reconstruction: A GETTEC prospective multicentric study. Surg Oncol, 2018. 27(1): p. 23–30. [DOI] [PubMed] [Google Scholar]
- 21.Castellano A and Sharma A, Systematic Review of Validated Quality of Life and Swallow Outcomes after Transoral Robotic Surgery. Otolaryngol Head Neck Surg, 2019. 161(4): p. 561–567. [DOI] [PubMed] [Google Scholar]
- 22.Checcoli E, et al. , Reconstructive head and neck surgery: oncological and functional results. Tumori, 2013. 99(4): p. 493–9. [DOI] [PubMed] [Google Scholar]
- 23.Dzioba A, et al. , Functional and quality of life outcomes after partial glossectomy: a multi-institutional longitudinal study of the head and neck research network. J Otolaryngol Head Neck Surg, 2017. 46(1): p. 56. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Machtay M, et al. , Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol, 2008. 26(21): p. 3582–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Seikaly H, et al. , Functional outcomes after primary oropharyngeal cancer resection and reconstruction with the radial forearm free flap. Laryngoscope, 2003. 113(5): p. 897–904. [DOI] [PubMed] [Google Scholar]
- 26.Wilson JA, Carding PN, and Patterson JM, Dysphagia after nonsurgical head and neck cancer treatment: patients’ perspectives. Otolaryngol Head Neck Surg, 2011. 145(5): p. 767–71. [DOI] [PubMed] [Google Scholar]
- 27.Edge SB and Compton CC, The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol, 2010. 17(6): p. 1471–4. [DOI] [PubMed] [Google Scholar]
- 28.Alias A and Henry M, Psychosocial Effects of Head and Neck Cancer. Oral Maxillofac Surg Clin North Am, 2018. 30(4): p. 499–512. [DOI] [PubMed] [Google Scholar]
- 29.Fan CY, et al. , Risk of depressive disorder among patients with head and neck cancer: A nationwide population-based study. Head Neck, 2018. 40(2): p. 312–323. [DOI] [PubMed] [Google Scholar]
- 30.Beers E, Lee Nilsen M, and Johnson JT, The Role of Patients: Shared Decision-Making. Otolaryngol Clin North Am, 2017. 50(4): p. 689–708. [DOI] [PubMed] [Google Scholar]
- 31.Jabbour J, et al. , The relationship between role preferences in decision-making and level of psychological distress in patients with head and neck cancer. Patient Educ Couns, 2018. 101(10): p. 1736–1740. [DOI] [PubMed] [Google Scholar]
- 32.List MA, et al. , Prioritizing treatment outcomes: head and neck cancer patients versus nonpatients. Head Neck, 2004. 26(2): p. 163–70. [DOI] [PubMed] [Google Scholar]
- 33.Shuman AG, et al. , Patient Reflections on Decision Making for Laryngeal Cancer Treatment. Otolaryngol Head Neck Surg, 2017. 156(2): p. 299–304. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Heft Neal ME, et al. , Predictors of survival in patients undergoing oropharyngeal surgery for cancer recurrence after radiation therapy. Eur Arch Otorhinolaryngol, 2020. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Data available upon request