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Importance: Transoral surgery (TOS) has become the primary surgical treatment for oropharyngeal squamous cell carcinoma (OPSCC). However, despite the increasing incidence of OPSCC in older patients, data regarding the safety and postoperative outcomes of TOS in this subgroup are lacking., Objective: This study aimed to evaluate the safety and postoperative outcomes of TOS in patients with OPSCC aged 70 years or older compared with younger individuals., Design, Setting, and Participants: This retrospective cohort study included patients with microscopic diagnostic confirmation of invasive OPSCC diagnosed between 2010 and 2021. Data were obtained from the US National Cancer Database. Data were analyzed in March 2024., Exposure: Minimally invasive TOS not converted to an open approach., Main Outcomes and Measures: Multivariable logistic and linear regression models were constructed to compare postoperative outcomes, adjusting for baseline patient and tumor characteristics. The results are reported as odds ratios (ORs) or mean differences with corresponding 95% CI, as appropriate., Results: A total of 10 430 patients (mean [SD] age, 60.7 [9.6] years; 8744 [83.8%] male) were included, with 1808 patients (17.3%) aged at least 70 years. No clinically meaningful difference was observed in terms of postoperative mortality at 30 days (adjusted OR, 1.24; 95% CI, 0.65-2.33) or 90 days (adjusted OR, 1.11; 95% CI, 0.65-1.87). Patients aged 70 years or older were less likely to undergo adjuvant radiotherapy (adjusted OR, 0.69; 95% CI, 0.57-0.83) and chemotherapy (adjusted OR, 0.63; 95% CI, 0.51-0.77). In addition, the adjuvant treatment was more frequently not administered in the older population due to patient refusal or comorbidities, despite being clinically indicated (radiotherapy: adjusted OR, 1.36; 95% CI, 1.05-1.77; chemotherapy: adjusted OR, 1.70; 95% CI, 1.17-2.45). No meaningful differences were observed regarding the remaining study outcomes, apart from a slightly longer hospitalization time for older patients, with an adjusted mean difference of 0.39 (95% CI, 0.05-0.74) days., Conclusions and Relevance: Findings from this study suggest that age was not independently associated with postoperative mortality in older patients undergoing TOS for OPSCC. However, older patients less frequently received adjuvant radiotherapy and chemotherapy compared with younger patients, and future studies should be conducted to examine the impact on long-term survival.

Importance: Patients with unknown primary squamous cell carcinoma (CUP) with cervical metastases typically receive comprehensive radiotherapy (RT) of the pharynx and bilateral neck. Typically, these patients receive comprehensive RT of the pharynx and bilateral neck that may produce treatment-related toxic effects., Objective: To determine whether localization of occult oropharyngeal cancers with transoral robotic surgery (TORS) combined with reduced pharyngeal and neck RT volumes provides acceptable disease control., Design, Setting, and Participants: This phase 2, single-group nonrandomized controlled trial at a single institution accrued 32 prospective participants with p16-positive CUP without a primary squamous cell carcinoma on examination and imaging from 2017 to 2019, and 24-month follow-up. The data analysis was conducted from January 2021 to June 2022., Intervention: Diagnostic- (n = 13) or therapeutic-intent (n = 9) TORS, with pharyngeal-sparing radiotherapy (PSRT) prescribed for negative margins or pT0, and unilateral neck RT (UNRT) prescribed for unilateral lymphadenopathy with lateralized primary tumor or pT0., Main Outcomes and Measures: Out-of-radiation treatment volume failure (<15% was hypothesized to be acceptable) and reports of local and regional recurrence, overall survival, toxic effects, swallowing outcomes (per the MD Anderson Dysphagia Inventory), and videofluoroscopic swallow (per Dynamic Imaging Grade of Swallowing Toxic Effects [DIGEST]) ratings., Results: The study sample comprised 22 patients (mean [SD] age, 59.1 [5.7] years; 3 [14%] females and 19 [86%] male) with CUP. Of these, 19 patients (86%) had tumor stage cN1; 2 (9%), cN2; and 1 (5%), cN3. Five patients (23%), 14 patients (64%), and 3 patients (13%) had 0, 1, or 2 primary tumors, respectively. Twenty patients received RT; of these, 9 patients (45%) underwent PSRT and 10 patients (50%), UNRT. In the diagnostic-intent group, 8 patients (62%) and 5 patients (38%) underwent RT and RT-concurrent chemotherapy, respectively. In the therapeutic-intent group, 6 patients (67%) and 1 patient (11%) received adjuvant RT-concurrent chemotherapy, respectively; 2 patients declined RT. Two-year out-of-radiation treatment volume failure, locoregional control, distant metastasis control, and overall survival were 0%, 100%, 95%, and 100%, respectively. Grade 3 or 4 surgical, acute, and late toxic effects occurred in 2 (9%), 5 (23%), and 1 (5%) patients, respectively. PSRT was associated with lower RT dose to superior constrictors (37 vs 53 Gy; mean difference, 16 Gy; 95% CI, 6.4, 24.9), smaller decline in swallowing scores during treatment (19.3 vs 39.7; mean difference, -20.4; 95% CI, -34.1 to -6.1), and fewer patients with worsening DIGEST grade on findings of videofluoroscopic swallow studies at 2 years (0% vs 60%; difference, 60%; 95% CI, 30% to 90%)., Conclusions and Relevance: These findings indicate that TORS for p16-positive CUP allows RT volume deintensification with excellent outcomes and support future investigation in randomized clinical trials., Trial Registration: ClinicalTrials.gov Identifier: NCT03281499.

Importance: The utility of preoperative circulating tumor tissue-modified viral human papillomavirus DNA (TTMV-HPV DNA) levels in predicting human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) disease burden is unknown., Objective: To determine if preoperative circulating tumor HPV DNA (ctHPVDNA) is associated with disease burden in patients with HPV+ OPSCC who have undergone transoral robotic surgery (TORS)., Design, Setting, and Participants: This cross-sectional study comprised patients with HPV+ OPSCC who underwent primary TORS between September 2021 and April 2023 at one tertiary academic institution. Patients with treatment-naive HPV+ OPSCC (p16-positive) and preoperative ctHPVDNA levels were included, and those who underwent neck mass excision before ctHPVDNA collection were excluded., Main Outcomes and Measures: The main outcome was the association of increasing preoperative ctHPVDNA levels with tumor size and lymph node involvement in surgical pathology. The secondary outcome was the association between preoperative ctHPVDNA levels and adverse pathology, which included lymphovascular invasion, perineural invasion, or extranodal extension., Results: A total of 70 patients were included in the study (65 men [93%]; mean [SD] age, 61 [8] years). Baseline ctHPVDNA levels ranged from 0 fragments/milliliter of plasma (frag/mL) to 49 452 frag/mL (median [IQR], 272 [30-811] frag/mL). Overall, 58 patients (83%) had positive results for ctHPVDNA, 1 (1.4%) had indeterminate results, and 11 (15.6%) had negative results. The sensitivity of detectable ctHPVDNA for identifying patients with pathology-confirmed HPV+ OPSCC was 84%. Twenty-seven patients (39%) had pathologic tumor (pT) staging of pT0 or pT1, 34 (49%) had pT2 staging, and 9 patients (13%) had pT3 or pT4 staging. No clinically meaningful difference between detectable and undetectable preoperative ctHPVDNA cohorts was found for tumor size or adverse pathology. Although the median preoperative ctHPVDNA appeared to be higher in pT2 through pT4 stages and pN1 or pN2 stages, effect sizes were small (pT stage: η2, 0.002 [95% CI, -1.188 to 0.827]; pN stage: η2, 0.043 [95% CI, -0.188 to 2.600]). Median preoperative log(TTMV-HPV DNA) was higher in active smokers (8.79 [95% CI, 3.55-5.76]), compared with never smokers (5.92 [95% CI, -0.97 to 1.81]) and former smokers (4.99 [95% CI, 0.92-6.23]). Regression analysis did not show an association between tumor dimension or metastatic lymph node deposit size and preoperative log(TTMV-HPV DNA). After univariate analysis, no association was found between higher log(TTMV-HPV DNA) levels and adverse pathology., Conclusions and Relevance: In this cross-sectional study, preoperative ctHPVDNA levels were not associated with disease burden in patients with HPV+ OPSCC who underwent TORS.

Importance: Transoral robot-assisted surgery (TORS) continues to have a major role in the treatment of oropharyngeal cancer. As new iterations of robotic technology are increasingly utilized, it is important to share learning experiences and clinical outcomes data, to optimize technical efficiency and clinical care., Observations: This was a retrospective review of a large academic institution's initial clinical use of the da Vinci Single Port (SP) compared with the da Vinci Si (Si) system. A total of 205 TORS cases were reviewed: 109 in the SP group (November 22, 2018, through September 30, 2020), and 96 in the Si group (January 1, 2016, through November 12, 2018). Both groups had comparable operative times, rates of postoperative pharyngeal hemorrhage, length of hospital stay, and duration of nasogastric feeding tube use. There was no difference in pathological characteristics, rates of positive margins, or indications for or time to initiation of adjuvant therapy between the groups. The collective experience of 6 faculty members-who have trained 139 TORS surgeons for the SP system rollout-was compiled to provide a summary of learning experiences and technical notes on safe and efficient operation of the SP system., Conclusions and Relevance: This Review found that the functional and oncologic outcomes were comparable between TORS cases performed with the Si and SP systems, and they had similar complication rates. Recognized advantages of the SP over the Si system include the availability of bipolar-energized instruments, a usable third surgical arm, and improved camera image quality.

Importance: Efforts are underway to deintensified treatment protocols for patients with human papillomavirus virus-associated oropharyngeal squamous cell carcinoma (HPV-OPSCC) to achieve similar excellent oncologic outcomes while reducing treatment-related adverse effects. Transoral robotic surgery (TORS) as primary treatment often requires adjuvant therapy due to the high incidence of nodal metastasis. Treatment with neoadjuvant chemotherapy followed by TORS and neck dissection (NECTORS), reserving radiation therapy for salvage, yields excellent oncologic outcomes., Objective: To assess patient-reported quality of life (QOL) and functional outcomes among patients with HPV-OPSCC who undergo NECTORS., Design, Settings, and Participants: This was a multicenter prospective cohort study of patients with HPV-OPSCC treated with the NECTORS protocol in 2017 to 2022. Consecutive patients with stage III or IVa HPV-OPSCC treated with NECTORS in 2017 to 2022 who had completed the primary QOL questionnaire at baseline and at least once during the 24-month follow-up period were included. Ninety-four patients were eligible, and 67 were included in the analyses., Outcome Measures: QOL questionnaires at baseline, and at month 1, 3, 6, 12, 18, and 24 posttreatment. Global score on the 30-item European Organization for Research and Treatment of Cancer Core quality of life questionnaire (EORTC QLQ-C30) was the primary outcome; the head and neck extension module (EORTC QLQ-HN35); the MD Anderson Dysphagia Inventory for dysphagia-related QOL; and the Decision Regret Scale were also used. Paired t tests assessed change between the baseline and 12- or 24-month patient-reported outcomes., Results: Among the study population of 67 patients (median [range] age, 63 [58-67] years; 54 [80.6%] male) with HPV-OPSCC, the most frequent cancer subsites were palatine tonsil (41 [61%]) and base of tongue (26 [39%]); none required adjuvant RT. Global QOL at 24 months improved compared with baseline (mean difference, 9.49; 95% CI, 2.45 to 16.53). All EORTC QLQ-C30 functional scores returned to baseline or improved within 3 to 6 months posttreatment and remained stable at 24 months. EORTC QLQ-HN35 symptom scale scores improved or were stable at 24 months. The MD Anderson Dysphagia Inventory scores demonstrated no significant difference between baseline and month 12 for global scores (mean difference, 6.15; 95% CI, -4.18 to 16.49) and composite scores (mean difference, 2.73; 95% CI, -1.62 to 7.09). Median (range) score on the Decision Regret Scale was 5 of 100 (0-30), representing mild overall regret., Conclusion and Relevance: The findings of this multicenter cohort study indicate that use of the NECTORS protocol is associated with excellent QOL outcomes. QOL measures returned to baseline levels or were better than baseline, which represents positive outcomes for patients with HPV-OPSCC who undergo this treatment regimen.

Importance: Oncologic outcomes are similar for patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with primary surgery or radiotherapy. However, comparative differences in long-term patient-reported outcomes (PROs) between modalities are less well established., Objective: To determine the association between primary surgery or radiotherapy and long-term PROs., Design, Setting, and Participants: This cross-sectional study used the Texas Cancer Registry to identify survivors of OPSCC treated definitively with primary radiotherapy or surgery between January 1, 2006, and December 31, 2016. Patients were surveyed in October 2020 and April 2021., Exposures: Primary radiotherapy and surgery for OPSCC., Main Outcomes and Measures: Patients completed a questionnaire that included demographic and treatment information, the MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) module, the Neck Dissection Impairment Index (NDII), and the Effectiveness of Auditory Rehabilitation (EAR) scale. Multivariable linear regression models were performed to evaluate the association of treatment (surgery vs radiotherapy) with PROs while controlling for additional variables., Results: Questionnaires were mailed to 1600 survivors of OPSCC identified from the Texas Cancer Registry, with 400 responding (25% response rate), of whom 183 (46.2%) were 8 to 15 years from their initial diagnosis. The final analysis included 396 patients (aged ≤57 years, 190 [48.0%]; aged >57 years, 206 [52.0%]; female, 72 [18.2%]; male, 324 [81.8%]). After multivariable adjustment, no significant differences were found between surgery and radiotherapy outcomes as measured by the MDASI-HN (β, -0.1; 95% CI, -0.7 to 0.6), NDII (β, -1.7; 95% CI, -6.7 to 3.4), and EAR (β, -0.9; 95% CI -7.7 to 5.8). In contrast, less education, lower household income, and feeding tube use were associated with significantly worse MDASI-HN, NDII, and EAR scores, while concurrent chemotherapy with radiotherapy was associated with worse MDASI-HN and EAR scores., Conclusions and Relevance: This population-based cohort study found no associations between long-term PROs and primary radiotherapy or surgery for OPSCC. Lower socioeconomic status, feeding tube use, and concurrent chemotherapy were associated with worse long-term PROs. Further efforts should focus on the mechanism, prevention, and rehabilitation of these long-term treatment toxicities. The long-term outcomes of concurrent chemotherapy should be validated and may inform treatment decision making.

Importance: Previously published work reported independent benefit of maintenance of oral intake (eat) and swallowing exercise adherence (exercise) during radiotherapy (RT) on diet and functional outcomes. The current study seeks to validate the authors' previously published findings in a large contemporary cohort of patients with oropharynx cancer (OPC) and address limitations of the prior retrospective study using prospective, validated outcome measures., Objective: To examine the longitudinal association of oral intake and swallowing exercise using validated, clinician-graded and patient-reported outcomes., Design, Setting, and Participants: Secondary analysis of a prospective OPC registry including patients who underwent primary RT/chemoradiotherapy (CRT) or primary transoral robotic surgery plus RT/CRT for OPC at a single-institution comprehensive cancer center., Exposures: Adherence to speech pathology swallowing intervention during RT coded as (1) eat: oral intake at end of RT (nothing by mouth [NPO]; partial oral intake [PO], with feeding tube [FT] supplement; full PO); and (2) exercise: swallowing exercise adherence (nonadherent vs partial/full adherence)., Main Outcomes and Measures: Feeding tube and diet (Performance Status Scale for Head and Neck Cancer) patient-reported swallowing-related quality of life (MD Anderson Dysphagia Inventory; MDADI) and clinician-graded dysphagia severity grade (videofluoroscopic Dynamic Imaging Grade of Swallowing Toxicity; DIGEST) were collected at baseline, 3 to 6 months, and 18 to 24 months post-RT., Results: A total of 595 patients (mean [SD] age, 65 [10] years; 532 [89%] male) who underwent primary RT (111 of 595 [19%]), CRT (434 of 595 [73%]), or primary transoral robotic surgery plus RT/CRT (50 of 595 [8%]) were included in this cohort study. At the end of RT, 55 (9%) patients were NPO, 115 (19%) were partial PO, 425 (71%) were full PO, and 340 (57%) reported exercise adherence. After multivariate adjustment, subacute return to solid diet and FT were independently associated with oral intake (odds ratio [OR], 2.0; 95% CI, 1.0-4.1; OR, 0.1; 95% CI, 0.0-0.2, respectively) and exercise (OR, 2.9; 95% CI, 1.9-4.5; OR, 0.3; 95% CI, 0.1-0.5, respectively). Subacute MDADI (β = 6.5; 95% CI, 1.8-11.2), FT duration (days; β = -123.4; 95% CI, -148.5 to -98.4), and less severe dysphagia per DIGEST (OR, 0.6; 95% CI, 0.3-1.0) were independently associated with oral intake, while exercise was independently associated with less severe laryngeal penetration/aspiration per DIGEST-safety (OR, 0.7; 95% CI, 0.4-1.0). DIGEST grade associations with oral intake were not preserved long-term; however, exercise was associated with a higher likelihood of solid diet intake and better swallow safety per DIGEST., Conclusions and Relevance: The findings of this cohort study extend the authors' previously published findings that oral intake and swallowing exercise during RT are associated with favorable functional outcomes, now demonstrated with broader domains of function using validated measures. Patterns of benefit differed in this study. Specifically, better subacute recovery of swallow-related quality of life and less severe dysphagia were found among patients who maintained oral intake independent of exercise adherence, and shorter FT utilization and better long-term diet and swallowing safety were found among those who exercised independent of oral intake.

Importance: The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown., Objective: To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC., Design, Setting, and Participants: This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16-positive OPSCC between February 13, 2018, and November 17, 2020. Patients had up to 3 years of follow-up., Interventions: Primary RT (consisting of 60 Gy of RT with concurrent weekly cisplatin in node-positive patients) vs TOS and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings)., Main Outcomes and Measures: The primary end point was overall survival (OS) compared with a historical control. Secondary end points included progression-free survival (PFS), quality of life, and toxic effects., Results: Overall, 61 patients were randomized (30 [49.2%] in the RT arm and 31 [50.8%] in the TOS and ND arm; median [IQR] age, 61.9 [57.2-67.9] years; 8 women [13.6%] and 51 men [86.4%]; 31 [50.8%] never smoked). The trial began in February 2018, and accrual was halted in November 2020 because of excessive toxic effects in the TOS and ND arm. Median follow-up was 17 months (IQR, 15-20 months). For the OS end point, there were 3 death events, all in the TOS and ND arm, including the 2 treatment-related deaths (0.7 and 4.3 months after randomization, respectively) and 1 of myocardial infarction at 8.5 months. There were 4 events for the PFS end point, also all in the TOS and ND arm, which included the 3 mortality events and 1 local recurrence. Thus, the OS and PFS data remained immature. Grade 2 to 5 toxic effects occurred in 20 patients (67%) in the RT arm and 22 (71%) in the TOS and ND arm. Mean (SD) MD Anderson Dysphagia Inventory scores at 1 year were similar between arms (85.7 [15.6] and 84.7 [14.5], respectively)., Conclusions and Relevance: In this randomized clinical trial, TOS was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year. Long-term follow-up is required to assess OS and PFS outcomes., Trial Registration: Clinicaltrials.gov Identifier: NCT03210103.

Importance: Understanding patient-specific risk of adverse histopathologic findings after primary surgery for human papillomavirus (HPV)-positive oropharynx squamous cell carcinoma (OPSCC) may help guide patient consultations., Objective: To determine the likelihood of adverse histopathologic features that may indicate adjuvant radiotherapy or chemoradiotherapy after primary surgery for HPV-positive OPSCC according to 2021 National Comprehensive Cancer Network guidelines., Design, Setting, and Participants: This retrospective cohort study was performed at a single academic tertiary care center. Of 258 patients who underwent transoral robotic surgery (TORS) from March 1, 2012, to March 1, 2021, 136 consecutive, treatment-naive patients with HPV-positive OPSCC without obvious clinical extranodal extension (ENE) who underwent definitive TORS and neck dissection were included in the analysis. Indications for surgical treatment included non-deeply infiltrative oropharynx tumors, minimal soft palate involvement, and low suspicion for pathologic ENE., Exposures: Primary site TORS with neck dissection., Main Outcomes and Measures: The primary outcomes were the adverse histopathologic features of pathologic ENE and positive surgical margins (PSM) that are indications for possible adjuvant chemoradiotherapy. Outcomes were compared among varying American Joint Committee on Cancer 7th edition (AJCC-7) T and N categories and patient clinical characteristics., Results: Of the 136 patients included in the analysis (113 men [83.1%]; median age, 63 [interquartile range, 55-70] years), 109 (80.1%) had at least 1 indication for possible adjuvant radiotherapy. Twenty-seven patients (19.9%) had pathologic ENE and 10 (7.3%) had PSM. Thirty-four patients (25.0%) had pathologic ENE and/or PSM, whereas 3 (2.2%) had both. Age, smoking history, history of alcohol consumption, and clinical T category were not associated with pathologic ENE, PSM, lymphovascular invasion, perineural invasion, or pN2 category or greater. The proportion of pathologic ENE varied by clinical N category: 0 of 16 for cN0, 8 of 48 (16.7%) for cN1, 3 of 23 (13.0%) for cN2a, and 16 of 45 (35.6%) for cN2b. Compared with patients with cN1-cN2a disease, patients with cN2b disease had higher odds of pathologic ENE (odds ratio, 3.01; 95% CI, 1.14-8.10). Clinical and pathologic N category were concordant in 77 patients (56.6%), whereas 42 (30.9%) were upstaged and 17 (12.5%) were downstaged., Conclusions and Relevance: In this cohort study, approximately one-quarter of carefully selected patients with HPV-positive OPSCC without obvious clinical ENE undergoing primary surgery had pathologic ENE and/or PSM. Patients with AJCC-7 cT0-cT2 cN0-cN2b disease, especially cN0-cN2a, without signs of clinical ENE may represent appropriate candidates for primary surgery when avoidance of adjuvant chemotherapy and/or reduction of adjuvant radiotherapy dose/extent are the goals.

Importance: Regional lymph node metastasis remains an important prognostic factor in patients with oropharyngeal squamous cell carcinoma (OPSCC). Although survival among patients with regional metastasis in human papillomavirus (HPV)-related OPSCC is more favorable compared with patients who are HPV negative, prognostic variables associated with failure in patients with single-node metastasis are not known., Objective: To evaluate recurrence and survival in patients with HPV-related OPSCC with single-lymph node metastasis treated with transoral surgery., Design, Setting, and Participants: A retrospective cohort study was conducted of 207 adults with newly diagnosed p16-positive OPSCC and pathology-confirmed single-node disease who underwent surgical resection with or without adjuvant therapy at 2 tertiary academic medical centers from January 1, 2007, to December 31, 2016. Statistical analysis was performed from September 1, 2018, to September 1, 2020., Interventions: Surgery alone (n = 59), surgery with adjuvant radiation (n = 75), or surgery with adjuvant chemoradiation (n = 73)., Main Outcomes and Measures: The primary outcome was regional recurrence. Secondary outcomes included overall survival, any recurrence, and identification of factors associated with regional recurrence and overall survival., Results: Among 207 patients, 178 (86%) were men, with a median age of 57 years (range, 35-82 years) at the time of surgery. Median follow-up was 36.2 months (range, 7-127 months). Regional recurrence occurred in 11 patients (5%). Of these, 1 patient (9%) was lost to follow-up after diagnosis, 1 (9%) was treated with palliative chemotherapy, and 9 (82%) were treated with curative intent. Ultimately, 7 patients received successful salvage treatment, and 3 died with disease. Overall, there were 21 patients (10%) with any recurrence, with 4 patients (19%) experiencing local recurrence, 11 (52%) experiencing regional recurrence, and 6 (29%) experiencing distant metastasis. The 5-year overall survival was 95% (95% CI, 89%-98%) for all patients. Older age (odds ratio [OR], 1.2; 95% CI, 1.1-1.2), advanced T stage (OR, 3.5; 95% CI, 0.9-14.0), and positive margins (OR, 10.9; 95% CI, 1.8-67.5) were associated with increased regional recurrence. Extranodal extension (OR, 0.2; 95% CI, 0.04-0.8), lymph node size greater than 3 cm (OR, 0.2; 95% CI, 0.1-0.7), and adjuvant therapy (OR, 0.08; 95% CI, 0.02-0.4) were associated with decreased regional recurrence. Advanced comorbidities (hazard ratio, 6.20; 95% CI, 1.4-27.7), lymphovascular invasion (hazard ratio, 4.7; 95% CI, 1.0-21.2), and regional recurrence (hazard ratio, 16.0; 95% CI, 3.1-82.0) were associated with worse overall survival., Conclusions and Relevance: The findings of this cohort study suggest that patients with HPV-related OPSCC and single-node disease undergoing surgical resection with or without adjuvant treatment have excellent survival. Adjuvant therapy appears to improve regional control. Among patients with regional recurrence of OPSCC, there is a high rate of successful salvage treatment.

Importance: While early epidemiologic studies ascribed increases in the incidence of human papillomavirus-associated oropharyngeal cancers to middle-aged patients, recent analyses have demonstrated an increasing median age of diagnosis. Treatment of patients older than 70 years is controversial as their inclusion in the practice-defining clinical trials has been limited and the survival benefit conferred by chemotherapy may be outweighed by treatment toxic effects., Objective: To assess the oncologic outcomes of older adults with human papillomavirus-associated oropharyngeal cancer who underwent upfront transoral robotic surgery and pathologic characteristics-guided adjuvant therapy in a large cohort of patients with close follow-up., Design, Setting, and Participants: A retrospective cohort analysis was conducted in a tertiary care academic medical center between January 1, 2010, and December 30, 2017. Patients aged 70 years or older at time of diagnosis with biopsy-proven and surgically resectable p16-positive oropharyngeal cancers were included. Data analysis was conducted from March 1 to June 1, 2020., Exposures: Transoral robotic surgery oropharyngeal resection and neck dissection with pathologic characteristic-guided adjuvant therapy., Main Outcomes and Measures: Three-year estimates of disease-specific survival, overall survival, and disease-free survival, as well as rates of adjuvant therapy (radiotherapy and chemoradiotherapy) and perioperative complications., Results: Seventy-seven patients were included (median age, 73.0; interquartile range, 71.0-76.0; range, 70-89 years); of these, 58 were men (75.3%). Perioperative mortality was 1.3% and the rate of oropharyngeal hemorrhage was 2.6%. Twenty-seven patients (35.1%) underwent postoperative radiotherapy and 20 patients (26.0%) underwent postoperative chemoradiotherapy. The median length of follow-up was 39.6 (range, 0.1-96.2) months, and the 3-year estimates of survival were 92.4% (95% CI, 82.4%-96.9%) for disease-specific survival, 90.0% (95% CI, 79.4%-95.0%) for overall survival, and 84.3% (95% CI, 73.4%-91.0%) for disease-free survival., Conclusions and Relevance: The findings of this cohort study suggest that transoral robotic surgery and pathologic characteristic-guided adjuvant therapy can provide beneficial survival outcomes, infrequent perioperative mortality, and, for most carefully selected older adults, obviate the need for chemotherapy.

Importance: Transoral robotic surgery has been widely adopted since approval by the US Food and Drug Administration in December 2009, despite limited comparative data., Objective: To compare the long-term outcomes of transoral robotic surgery with those of nonrobotic surgery for patients with early-stage oropharyngeal cancer., Design, Setting, and Participants: A retrospective cohort comparative effectiveness analysis was performed of patients in the National Cancer Database with clinical T1 and T2 oropharyngeal squamous cell carcinoma diagnosed between January 1, 2010, and December 31, 2015, who underwent definitive robotic and nonrobotic surgery. Multivariable Cox proportional hazards regression analysis and propensity score matching were performed in patients with known human papillomavirus status to adjust for patient- and disease-related covariates. Survival after robotic and nonrobotic surgery was also compared in 3 unrelated cancers: prostate, endometrial, and cervical cancer. Statistical analysis was performed from April 10, 2019, to May 21, 2020., Main Outcomes and Measures: Overall survival., Results: Of 9745 patients (7652 men [78.5%]; mean [SD] age, 58.8 [9.6] years) who met inclusion criteria, 2694 (27.6%) underwent transoral robotic surgery. There was a significant increase in the use of robotic surgery from 18.3% (240 of 1309) to 35.5% (654 of 1841) of all surgical procedures for T1 and T2 oropharyngeal cancers from 2010 to 2015 (P = .003). Robotic surgery was associated with lower rates of positive surgical margins (12.5% [218 of 1746] vs 20.3% [471 of 2325]; P < .001) and lower use of adjuvant chemoradiotherapy (28.6% [500 of 1746] vs 35.7% [831 of 2325]; P < .001). Among 4071 patients with known human papillomavirus status, robotic surgery was associated with improved overall survival compared with nonrobotic surgery in multivariable Cox proportional hazards regression (hazard ratio [HR], 0.74; 95 CI, 0.61-0.90; P = .002). Similar results were seen when analyzing only the subset of facilities offering both robotic and nonrobotic surgery. The 5-year overall survival was 84.8% vs 80.3% among patients undergoing robotic vs nonrobotic surgery in propensity score-matched cohorts (P = .001). By contrast, there was no evidence that robotic surgery was associated with improved survival in other cancers, such as prostate cancer (HR, 0.92; 95% CI, 0.79-1.07; P = .26), endometrial cancer (HR, 0.97; 95% CI, 0.90-1.04; P = .36), and cervical cancer (HR, 1.27; 95% CI, 0.96-1.69; P = .10)., Conclusions and Relevance: This study suggests that transoral robotic surgery was associated with improved surgical outcomes and survival compared with nonrobotic surgery in patients with early-stage oropharyngeal cancer. Evaluation in comparative randomized trials is warranted.

Importance: Human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) is a distinct form of head and neck squamous cell carcinoma (HNSCC) with its own American Joint Committee on Cancer staging system. However, pathologic risk stratification for HPV+ OPSCC largely remains based on the experience with HPV-unassociated HNSCC., Objective: To compare the survival discrimination of traditional pathologic risk stratification for both HPV+ OPSCC and HPV-unassociated HNSCC and derive a novel pathologic risk stratification system for HPV+ OPSCC with improved survival discrimination., Design, Setting, and Participants: In this retrospective cohort study, we used the National Cancer Database to identify 15 324 patients diagnosed with nonmetastatic HNSCC between January 1, 2010, and December 31, 2013, who were treated with upfront surgery and neck dissection. We compared traditional pathologic risk stratification for HPV+ OPSCC and HPV-unassociated HNSCC and then derived a novel pathologic risk stratification system. Analyses were performed from July 1, 2018, to January 31, 2019., Exposures: Definitive primary surgical resection and neck dissection., Main Outcomes and Measures: Survival discrimination of pathologic risk stratification systems measured with concordance indices., Results: This retrospective cohort study included 15 324 patients (10 779 men and 4545 women; mean [SD] age, 59.9 [11.8] years) with surgically treated nonmetastatic HNSCC. Separation of survival curves for HPV-unassociated HNSCC using traditional pathologic risk stratification (5-year overall survival for the low-, intermediate-, and high-risk groups) were 76.2%, 54.5%, and 40.9%, respectively. Separation curves for HPV+ OPSCC were 93.2%, 88.9%, and 83.7%, respectively. Human papillomavirus-unassociated HNSCC had a concordance index of 0.68, whereas HPV+ OPSCC had a concordance index of 0.58. A novel risk stratification system for HPV+ OPSCC that more closely fits actual survival rates for HPV+ OPSCC was derived. The system incorporated the composite number of pathologic adverse features. This composite risk stratification system was associated with an improved concordance index of 0.67 for HPV+ OPSCC. Adjuvant treatment with radiation was not associated with improved survival for patients categorized as low risk according to the new risk stratification system, but this treatment was associated with improved survival for patients in the intermediate- and high-risk groups., Conclusions and Relevance: Traditional pathologic risk stratification shows poor survival discrimination for HPV+ OPSCC and classifies many patients with an excellent prognosis as high risk. We derived a novel composite pathologic risk stratification system for HPV+ OPSCC that may be associated with improved survival discrimination.

Importance: Human papillomavirus (HPV)-negative oropharyngeal squamous cell carcinoma (OPSCC) has shown resistance to conventional concurrent chemoradiation (CRT) therapy and carries a relatively poor prognosis in comparison with HPV-positive disease, with decreased locoregional control and overall survival (OS). In the present analysis, we examine whether upfront surgical resection improves overall survival in a large national sample., Objective: To compare survival outcomes among patients with newly diagnosed cT1-2 N1-2b HPV-negative OPSCC when treated with primary surgical resection vs CRT., Design, Setting, and Participants: This was an observational study of factors associated with primary treatment modality were identified using multivariable logistic regression. Overall survival was compared using Kaplan-Meier analysis with log-rank tests, multivariable Cox regression, and propensity score matching. Statistical tests were 2-sided. Patients newly diagnosed as having cT1-2 N1-2b pathologically confirmed HPV-negative OPSCC in 2010 to 2012 were identified using the National Cancer Data Base, which includes more than 70% of patients newly diagnosed as having cancer in the United States., Exposures: Primary surgical resection vs definitive CRT., Main Outcomes and Measures: Overall survival., Results: We identified 1044 patients, among whom 460 (44.1%) received upfront surgery and 584 (55.9%) received CRT. Median age was 59 years (range, 25-90 years); 812 patients were male (77.8%), 232 were female (22.2%). Median follow-up was 30 months. Approximately 59% of surgical patients received adjuvant CRT. On multivariable Cox regression, upfront surgery was not associated with increased OS when compared with CRT (adjusted hazard ratio [HR], 1.01; 95% CI, 0.74-1.39; P = .93). Propensity score-matching identified a cohort of 822 patients and redemonstrated equivalent OS (HR, 1.14; 95% CI, 0.81-1.62; P = .46). Lack of OS benefit with upfront surgery persisted in a subset analysis of patients with margin-negative resection (HR, 0.97; 95% CI, 0.66-1.45; P = .88)., Conclusions and Relevance: In this observational study, OS was similar for patients with HPV-negative OPSCC when treated with primary surgery vs CRT. Most surgical patients received trimodal therapy with adjuvant CRT. Our data may have implications for future research focusing on optimal patient selection for surgery.

Importance: Survival rates for head and neck cancer have been relatively stable for several decades. Individualized prognostic indicators are needed to identify patients at risk for poorer outcomes., Objective: To determine whether biomarker levels in surgical drain fluid of patients with head and neck cancer are associated with poor cancer outcomes., Design, Setting, and Participants: This prospective cohort study enrolled patients with squamous cell carcinoma (SCC) of the oral cavity and oropharynx who required surgical treatment from April 1, 2011, to February 1, 2016, at a tertiary or academic care center. Twenty patients, including 14 with stage IV disease, had complete specimen collection. Differences in cytokine and MMP levels by disease outcomes were evaluated., Interventions: Patients underwent surgical treatment with drain placement as dictated by the standard of care. Drain fluid samples were collected every 8 hours postoperatively until drains were removed because of clinical criteria. Levels of cytokines and matrix metalloproteinases (MMPs) were measured using electrochemiluminescent, patterned array, multiplex technology., Main Outcomes and Measures: The primary clinical outcome measures were survival outcome and recurrence. The biomarkers measured included the cytokines basic fibroblastic growth factor, vascular endothelial growth factor isoform A, soluble fms-like tyrosine kinase-1 (sFlt-1), and placental growth factor (PIGF) and MMP-1, MMP-3, and MMP-9. Other clinical and pathologic cancer characteristics were recorded., Results: In this cohort of 20 patients with SCC (15 men and 5 women; mean [SD] age, 63.5 [9.9] years), a significant association with recurrence was found for levels of MMP-1 (relative difference between groups, 2.78; 95% CI, 1.23-6.29), MMP-3 (relative difference between groups, 5.29; 95% CI, 2.14-13.05), and sFlt-1 (relative difference between groups, 3.75; 95% CI, 1.84-7.65). No biomarkers were associated with disease outcome. Vascular endothelial growth factor isoform A was associated with nodal metastasis (relative difference between groups, 1.98; 95% CI, 1.12-3.51), and basic fibroblastic growth factor was associated with lymphovascular invasion (relative difference between groups, 1.74; 95% CI, 1.02-2.97)., Conclusions and Relevance: In this pilot sample of patients with SCC of the oral cavity and oropharynx, MMP-1, MMP-3, and sFlt-1 levels in wound fluid were associated with poor clinical cancer outcomes in the form of recurrence. This finding is consistent with the literature of tumor microenvironment in saliva, serum, and tumor tissue biomarkers. To our knowledge, this report is the first of such findings in surgical drain fluid, an easily accessible means of cytokine measurement. Measurement of these biomarkers in surgical fluid potentially represents a novel means of assessing cancer prognosis in this population.

Importance: The treatment of oropharyngeal cancer has undergone a paradigm shift in the past 2 decades, with an increase in the use of nonoperative treatment owing to poor functional outcomes associated with traditional surgical approaches. Transoral robotic surgery (TORS) allows surgical resection of oropharyngeal cancer (OPC) with less morbidity through a minimally invasive approach., Objective: To investigate the relationship among TORS and short- and long-term outcomes and costs in surgically treated patients with OPC., Design, Setting, and Participants: Retrospective cross-sectional analysis of 3573 patients who underwent an ablative procedure for OPC in 2010 to 2012 using the MarketScan Commercial Claim and Encounters database., Main Outcomes and Measures: The association between TORS and short- and long-term outcomes, length of hospitalization, and treatment-related costs was analyzed using descriptive statistics and multivariate regression modeling., Results: Transoral robotic surgery was performed in 304 surgical cases (8.5%); 94.7% of patients were 40 to 64 years old, and 70.7% were male. The use of TORS increased from 4.1% of surgical cases in 2010 to 13.2% of surgical cases in 2012. Patients who underwent TORS had a lower rate of tracheotomy during treatment (3.9% vs 11.4%), and posttreatment gastrostomy tube use (21.9% vs 34.2%), compared with patients undergoing non-TORS procedures. On multivariate analysis, TORS was not associated with significant differences in postoperative complications or length of hospitalization. There was no significant difference in the odds of receiving postoperative radiation therapy between patients who underwent TORS and those who did not; however, among patients receiving radiation therapy, chemoradiation was significantly less likely following TORS (odds ratio [OR], 0.52; 95% CI, 0.29-0.90). TORS was associated with significantly decreased odds of posttreatment gastrostomy (OR, 0.54; 95% CI. 0.30-0.95) and tracheostomy during treatment (OR, 0.17; 95% CI, 0.06-0.55) at 1 year, and was associated with significantly decreased overall treatment-related costs of care (mean incremental cost, -$22 724)., Conclusions and Relevance: The use of TORS for surgical resection of OPC is increasing in the United States and is associated with significantly lower use of adjuvant chemoradiation, late gastrostomy and tracheostomy dependence, and lower overall treatment-related costs of care. These data have implications for discussions of value in OPC care at a time of health care reform.

Importance: Transoral robotic surgery (TORS) is increasingly employed as a treatment option for squamous cell carcinoma of the oropharynx (OPSCC). Measures of surgical learning curves are needed particularly as clinical trials using this technology continue to evolve., Objective: To assess learning curves for the oncologic TORS surgeon and to identify the number of cases needed to identify the learning phase., Design, Setting, and Participants: A retrospective review of all patients who underwent TORS for OPSCC at the University of Pittsburgh Medical Center between March 2010 and March 2016. Cases were excluded for involvement of a subsite outside of the oropharynx, for nonmalignant abnormality or nonsquamous histology, unknown primary, no tumor in the main specimen, free flap reconstruction, and for an inability to define margin status., Exposures: Transoral robotic surgery for OPSCC., Main Outcomes and Measures: Primary learning measures defined by the authors include the initial and final margin status and time to resection of main surgical specimen. A cumulative sum learning curve was developed for each surgeon for each of the study variables. The inflection point of each surgeon's curve was considered to be the point signaling the completion of the learning phase., Results: There were 382 transoral robotic procedures identified. Of 382 cases, 160 met our inclusion criteria: 68 for surgeon A, 37 for surgeon B, and 55 for surgeon C. Of the 160 included patients, 125 were men and 35 were women. The mean (SD) age of participants was 59.4 (9.5) years. Mean (SD) time to resection including robot set-up was 79 (36) minutes. The inflection points for the final margin status learning curves were 27 cases (surgeon A) and 25 cases (surgeon C). There was no inflection point for surgeon B for final margin status. Inflection points for mean time to resection were: 39 cases (surgeon A), 30 cases (surgeon B), and 27 cases (surgeon C)., Conclusions and Relevance: Using metrics of positive margin rate and time to resection of the main surgical specimen, the learning curve for TORS for OPSCC is surgeon-specific. Inflection points for most learning curves peak between 20 and 30 cases.

Importance: Management of cervical lymph node metastasis without a known primary tumor is a diagnostic and treatment challenge for head and neck oncologists. Identification of the occult mucosal primary tumor minimizes the morbidity of treatment., Objective: To analyze the role of transoral robotic surgery (TORS) in facilitating the identification of a primary tumor site for patients presenting with squamous cell carcinoma of unknown primary (CUP). In addition, we assessed treatment deintensification by determining the number of patients who did not undergo definitive radiation therapy and chemotherapy., Design, Setting, and Participants: In this retrospective case series from January 2011 to September 2015, 60 consecutive patients with squamous cell CUP who underwent TORS-assisted endoscopy and ipsilateral neck dissection were included from an academic medical center and studied to study the rate success rate of TORS identifying occult mucosal malignancy., Main Outcomes and Measures: Success rate of identifying occult mucosal malignancy; usage of radiation therapy and chemotherapy., Results: Overall, 60 patients (mean [SD] age, 55.5 [8.9] years) were identified; 48 of the 60 patients (80.0%) had a mucosal primary identified during their TORS-assisted endoscopic procedure. The mean (SD) size of the identified mucosal primary lesions was 1.3 (0.1) cm. All mucosal primaries, when found, originated in the oropharynx including the base of tongue in 28 patients (58%), palatine tonsil in 18 patients (38%), and glossotonsillar sulcus in 2 patients (4%). Among patients in this study, 40 (67%) did not receive chemotherapy, and 15 (25%) did not receive radiation therapy., Conclusions and Relevance: Advances in transoral surgical techniques have helped identify occult oropharyngeal malignancies that traditionally have been treated with comprehensive radiation to the entire pharyngeal axis. We demonstrate the efficacy of a TORS-assisted approach to identify and surgically treat the primary tumor in patients presenting with CUP. In addition, patients managed with the TORS-assisted endoscopic approach benefit from surgical and pathological triage, which in turn results in deintensification of treatment by eliminating the need for chemotherapy in the majority of patients, as well as avoiding radiation therapy in select patients.

Importance: Hospital readmissions are a marker of surgical care delivery and quality that are progressively more scrutinized., Objective: To provide a comprehensive analysis of 30-day readmissions for patients with head and neck cancer who underwent free flap reconstruction to highlight the rate, causes, and associated patient risk factors., Design, Setting, and Participants: Retrospective cohort study at a single tertiary care academic institution. The study consisted of 249 patients who underwent microvascular reconstruction of a presumed head and neck oncologic defect from January 1, 2000, through June 30, 2014. Follow-up continued through July 30, 2014., Interventions: Microvascular reconstruction of an oncologic head and neck defect., Main Outcomes and Measures: Incidence of 30-day all-cause readmissions, patient risk factors, and readmission indications. Regression analyses were conducted to discern patient-level risk factors related to 30-day readmissions., Results: Among the 249 patients, the 30-day all-cause readmission rate was 14.5%, while the unplanned readmission rate was 11.6%. The most common reason for readmission was neck wound complications. Predictors of readmission following multivariable analysis were T4 pathologic stage (odds ratio [OR], 11.68; 95% CI, 1.37-99.81; P = .02) and having a tumor located in the oropharynx (OR, 4.64; 95% CI, 1.89-11.38; P = .001), hypopharynx (OR, 8.30; 95% CI, 1.52-45.24; P = .01), or larynx (OR, 10.97; 95% CI, 2.27-52.98; P = .003). Patients who were readmitted were more likely to experience neck wound complications (OR, 5.07; 95% CI, 1.31-19.57; P = .02) and undergo reoperation (OR, 47.20; 95% CI, 8.33-267.33; P < .001)., Conclusions and Relevance: In this study, advanced pathologic tumor staging and tumor location were associated with 30-day readmissions in patients with head and neck cancer who receive free flaps. Our results provide a benchmark for risk stratification that can be used in system-based practice improvements, health care cost savings, and postoperative patient counseling.

Importance: Few studies have examined quality-of-life (QOL) outcomes in patients who undergo transoral robotic surgery (TORS) alone (ie, without adjuvant radiotherapy or chemoradiotherapy)., Objective: To report QOL outcomes of patients with oropharyngeal squamous cell carcinoma who receive only TORS., Design, Setting, and Participants: Medical records for all patients undergoing TORS for treatment of primary oropharyngeal squamous cell carcinoma from May 1, 2010, to March 31, 2014, at a tertiary care academic cancer center were examined from June through September 2014. Thirty-four patients who did not receive adjuvant therapy after TORS were included in the study., Intervention: Primary surgical resection via TORS., Main Outcomes and Measures: The University of Washington Quality of Life, version 4, questionnaire was completed by patients preoperatively and at 1-, 6-, 12-, and 24-month intervals after TORS. Demographic, clinicopathologic, and follow-up data were collected., Results: Mean follow-up time was 14 months (May 1, 2010, to April 30, 2014). Most patients had T1 (20 [59%]) or T2 (13 [38%]) and N0 (13 [38%]) or N1 (16 [47%]) disease. Statistically significant improvement in QOL outcomes was noted in the following postoperative domains: chewing from 1 month (median, 50 [IQR, 50-100]) to 12 months (100 [IQR, 100-100]; P = .048), swallowing from 1 month (70 [IQR, 30-85]) to 6 months (100 [IQR, 70-100]; P = .047) and 1 to 24 months (100 [IQR, 70-100]; P = .048), pain from 1 month (38 [IQR, 25-75]) to 6 months (88 [IQR, 75-100]; P = .006) and 1 to 12 months after surgery (100 [IQR, 75-100]; P = .01), and activity from 1 month (63 [IQR, 50-88]) to 24 months (100 [IQR, 75-100]; P = .03). Two participants (6%) died during the follow-up period: 1 because of disease and 1 because of a myocardial infarction. Two patients (6%) required temporary gastrostomy tube placement, but none required tracheostomy., Conclusions and Relevance: Appropriately selected patients who undergo TORS alone for oropharyngeal squamous cell carcinoma experience acceptable short- and long-term QOL outcomes.

Importance: With an increasing incidence of oropharyngeal carcinoma and prevalence of transoral surgical techniques, postoperative bleeding, with its associated risk factors, deserves evaluation., Objective: To classify and review postoropharyngectomy hemorrhage rates and associated risk factors., Design, Setting, and Participants: Single-institution, multicenter retrospective medical chart review analyzing surgical procedures in 906 patients treated with transoral surgery for oropharyngeal carcinoma at a tertiary care, academic referral center from 1994 to 2012. Tumor stage, previous treatment, resection method, and transcervical external carotid branch ligation were analyzed in relationship to postoperative hemorrhage rate, and severity. A novel classification system was created, grading bleeding episodes as minor, intermediate, major, or severe based on management method and related sequelae., Results: Postoperative bleeding occurred in 5.4% of patients (49 of 906) with 67.3% of these (33 of 49) requiring operative intervention. Severe bleeding episodes were very rare (1.1% of patients). Transcervical external carotid system vessel ligation was performed with the primary resection in 15.6% of patients with no overall difference in bleeding rate or severity of bleeding in patients who underwent ligation vs those who did not (P = .21 and P = .66, respectively). Vessel ligation was performed more frequently in patients with a higher T stage (P = .002). In previously treated patients, severity of bleeding was decreased if vessels were ligated (P > .05). Higher T-stage tumors had a higher bleeding rate (P = .02). Bleeding rates were similar between those treated with laser (5.6%) and robotic (5.9%) oropharyngectomy (P = .80); however, patients with significantly higher T-stage tumors were treated with laser vs robot techniques (P < .001)., Conclusions and Relevance: Transoral resection of oropharyngeal carcinoma is safe, and severe life-threatening hemorrhage is rare. Although transcervical vessel ligation did not result in an overall decrease in bleeding rate, there is a trend toward reduced postoropharyngectomy bleeding severity with ligation. We recommend ligation for higher T-stage tumors, primary tonsil tumors, and patients undergoing revision surgery.

Importance: Traditional prognostic models for squamous cell carcinoma of the head and neck are based on the TNM staging system. However, there is growing evidence that tumor volume (TV) may be a more accurate predictor of outcome., Objective: To determine whether pathologic TV (pTV) in patients with oropharyngeal squamous cell carcinoma treated surgically is a more significant predictor of outcome compared with pathologic tumor (pT) stage., Design, Setting, and Participants: Review of patients whose treatment was managed between January 1, 1985, and December 2005 at a US tertiary referral cancer center. The participants included 159 patients who had undergone primary surgery for oropharyngeal squamous cell carcinoma and had 3 dimensions reported on histopathologic testing., Main Outcomes and Measures: The pTV was calculated as the product of the 3 dimensions expressed in cubic centimeters. For comparison of pT stage with pTV in outcome prediction, concordance indexes were generated using the bootstrap method (n = 1000) to quantify the predictive accuracy of recurrence and survival outcomes. Concordance indexes were then compared and a significant difference was considered when P < .05., Results: The median age of the patients was 59 years (range, 22-84 years) and 106 were male (67%). Sites of the tumors were base of the tongue (86 patients [54%]), tonsil (48 [30%]), soft palate (24 [15%]), and posterior pharyngeal wall (1 [1%]). The median follow-up time was 64 months (range, 1-272 months). The median tumor volume was 6.8 cm3 (range, 0.1-162.5 cm³). Pathologic TV was a significant predictor of disease-specific mortality. Unlike pT stage, pTV was a significant predictor of local recurrence, regional recurrence, and distant recurrence. Comparison of concordance indexes showed that pTV was a significantly better predictor of disease-specific mortality, local recurrence, and distant recurrence (all P < .05)., Conclusions and Relevance: Pathologic TV outperforms pT stage in the prediction of outcome following surgical treatment of oropharyngeal cancer. Tumor volume should be considered in the design of prospective surgical trials.

Importance: Because treatment for oropharyngeal squamous cell carcinoma (OPSCC), especially in patients of older age, is associated with decreased patient quality of life (QOL) after surgery, demonstration of a less QOL-impairing treatment technique would improve patient satisfaction substantially., Objective: To determine swallowing, speech, and QOL outcomes following transoral robotic surgery (TORS) for OPSCC., Design, Participants, and Setting: This prospective cohort study of 81 patients with previously untreated OPSCC was conducted at a tertiary care academic comprehensive cancer center., Interventions: Primary surgical resection via TORS and neck dissection as indicated., Main Outcomes and Measures: Patients were asked to complete the Head and Neck Cancer Inventory (HNCI) preoperatively and at 3 weeks as well as 3, 6, and 12 months postoperatively. Swallowing ability was assessed by independence from a gastrostomy tube (G-tube). Clinicopathologic and follow-up data were also collected., Results: Mean follow-up time was 22.7 months. The HNCI response rates at 3 weeks and 3, 6, and 12 months were 79%, 60%, 63%, and 67% respectively. There were overall declines in speech, eating, aesthetic, social, and overall QOL domains in the early postoperative periods. However, at 1 year post TORS, scores for aesthetic, social, and overall QOL remained high. Radiation therapy was negatively correlated with multiple QOL domains (P < .05 for all comparisons), while age older than 55 years correlated with lower speech and aesthetic scores (P < .05 for both). Human papillomavirus status did not correlate with any QOL domain. G-tube rates at 6 and 12 months were 24% and 9%, respectively. Greater extent of TORS (>1 oropharyngeal site resected) and age older than 55 years predicted the need for a G-tube at any point after TORS (P < .05 for both)., Conclusions and Relevance: Patients with OPSCC treated with TORS maintain a high QOL at 1 year after surgery. Adjuvant treatment and older age tend to decrease QOL. Patients meeting these criteria should be counseled appropriately.

Importance: Simulation-based standardized training is important for the clinical training of physicians practicing robotic surgery., Objective: To train robotic surgery-naïve student volunteers using the da Vinci Skills Simulator (dVSS) for transoral robotic surgery (TORS)., Design: Prospective inception cohort in 2012., Setting: Academic referral center., Participants: Sixteen medical student volunteers lacking experience in robotic surgery., Interventions: Participants trained with the dVSS in 12 exercises until competent, defined as an overall score of at least 91%. After a 1-, 3-, 5-, or 7-week postinitial training hiatus (n = 4 per group), participants reachieved competence on follow-up., Main Outcomes and Measures: Total training time (TTT) to achieve competency, total follow-up time (TFT) to reachieve competency, and performance metrics., Results: All participants became competent. The TTT distribution was normal based on the Anderson-Darling normality test (P > .50), but our sample was divided into a short training time (STT) group (n = 10 [63%]) and long training time (LTT) group (n = 6 [37%]). The mean (SD) TTT was 2.4 (0.6) hours for the STT group and 4.7 (0.5) hours for the LTT group. All participants reachieved competence with a mean TFT that was significantly shorter than TTT. There was no significant difference between STT and LTT in mean TFT at 1 and 3 weeks (P = .79), but the LTT group had a longer TFT at 5 and 7 weeks (P = .04) but with no difference in final follow-up scores (P = .12)., Conclusions and Relevance: Physicians in training can acquire robotic surgery competency. Participants who acquire skills faster regain robotic skills faster after a training hiatus, but, on retraining, all participants can regain equivalent competence. This information provides a benchmark for a simulator training program.

Importance: Surgical salvage may be the only viable treatment option for recurrent tumors of the oropharynx. To our knowledge, there have been no published reports directly comparing the oncologic and functional outcomes of patients with recurrent oropharyngeal squamous cell carcinoma (SCC) treated with transoral robotic-assisted surgery (TORS) with those treated with traditional open surgical approaches., Objective: To compare the oncologic and functional outcomes of patients with recurrent oropharyngeal SCC treated with TORS with those treated with traditional open surgical approaches., Design: Retrospective multi-institutional case-control study; study dates, March 2003 through October 2011., Setting: Four tertiary care institutions (University of Alabama at Birmingham; M. D. Anderson Cancer Center, Houston, Texas; Mayo Clinic, Rochester, Minnesota; and Henry Ford Hospital, Detroit, Michigan). PARTICIPANTS Sixty-four patients who underwent salvage TORS for recurrent oropharyngeal SCC were matched by TNM stage to 64 patients who underwent open salvage resection. INTERVENTION OR EXPOSURE: Salvage TORS for recurrent SCC of the oropharynx., Main Outcome and Measures: Patient demographics, operative data, functional, and oncologic outcomes were recorded and compared with a similarly TNM-matched patient group that underwent salvage surgical resection by traditional open surgical approaches. RESULTS Patients treated with TORS were found to have a significantly lower incidence of tracheostomy use (n = 14 vs n = 50; P < .001), feeding tube use (n = 23 vs n = 48; P < .001), shorter overall hospital stays (3.8 days vs 8.0 days; P < .001), decreased operative time (111 minutes vs 350 minutes; P < .001), less blood loss (49 mL vs 331 mL; P < .001), and significantly decreased incidence of positive margins (n = 6 vs n = 19; P = .007). The 2-year recurrence-free survival rate was significantly higher in the TORS group than in the open approach group (74% and 43%, respectively) (P = .01)., Conclusions and Relevance: This study demonstrates that TORS offers an alternative surgical approach to recurrent tumors of the oropharynx with acceptable oncologic outcomes and better functional outcomes than traditional open surgical approaches. This adds to the growing amount of clinical evidence to support the use of TORS in selected patients with recurrent oropharyngeal SCC as a feasible and oncologically sound method of treatment.

Objective: To determine the value of positron emission tomography (PET) with contrast-enhanced computed tomography (CT) in assessing the need for neck dissection by retrospectively reviewing the pathology reports of patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (SCC)., Design: Retrospective cohort study., Setting: Tertiary medical center., Patients: Seventy-seven patients with HPV-related SCC., Main Outcome Measures: Seventy-seven consecutive patients with a diagnosis of HPV-related SCC who were treated with radiotherapy as the primary treatment between August 2007 and October 2010 were retrospectively evaluated for radiologic and pathologic rate of persistence of nodal metastasis after completion of definitive radiotherapy. Pretreatment and posttreatment imaging included contrast-enhanced CT and PET. Response to treatment was measured on CT, PET at standardized uptake value (SUV) thresholds of 2 and 2.5, and PET/CT by a neuroradiologist in a blinded fashion. Then, the pathology report of the patients who underwent neck dissections was reviewed for nodal status after resection and correlated with the imaging findings., Results: Of the 77 patients, 67 met the study criteria, with an average follow-up PET/CT scan at 90.5 days after completion of radiotherapy. Ten patients did not undergo follow-up PET/CT imaging. Twenty patients underwent neck dissections after completion of radiation therapy. Of these 20 patients, 4 had persistent tumor and 16 did not have viable tumor. Using the final pathology report to correlate with imaging responses, CT had a negative predictive value (NPV) of 85.7% (95% CI, 48.7%-97.4%), PET with SUV thresholds of 2 had an NPV of 91.7% (95% CI, 64.6%-98.5%), PET with a cutoff SUV of 2.5 had an NPV of 85.7% (95% CI, 60.1%-96.0%), PET/CT with an SUV of 2 had an NPV of 100% (95% CI, 59.8%-100.0%), and PET/CT with an SUV of 2.5 had an NPV of 85.7% (95% CI, 48.7%-97.4%). The 47 patients who did not undergo neck dissection had a median follow-up of 26 months without an isolated neck failure. Analysis of all 67 patients in the cohort revealed the following values: CT had an NPV of 95.7% (95% CI, 85.8%-98.8%), PET with an SUV of 2 had an NPV of 98.2% (95% CI, 90.4%-99.7%), PET with an SUV of 2.5 had an NPV of 95.0% (95% CI, 86.3%-98.3%), PET/CT with an SUV of 2 had an NPV of 100.0% (95% CI, 92.0%-100.0%), and PET/CT with an SUV of 2.5 had an NPV of 95.7% (95% CI, 85.8%-98.8%)., Conclusions: Positron emission tomography combined with contrast-enhanced CT has a better NPV than either imaging modality alone in patients with HPV-associated oropharyngeal SCC. Furthermore, PET/CT with an SUV threshold of 2 used in patients with HPV-related SCC offers an imaging modality with a high NPV that may obviate the need for unnecessary neck dissections.

Objective: To evaluate local control following transoral robotic surgery (TORS) with the da Vinci Surgical System (Intuitive Surgical Inc) as a single treatment modality for oropharyngeal squamous cell carcinoma (OSCC)., Design: Prospective, single-center, observational study., Setting: Academic university health system and tertiary referral center., Patients: Thirty adults with previously untreated OSCC., Intervention: Transoral robotic surgery with staged neck dissection as indicated., Main Outcome Measures: Local control and margin status., Results: Thirty patients were enrolled with previously untreated OSCC and no prior head and neck radiation therapy. Follow-up duration was at least 18 months. At the time of diagnosis, 9 tumors were T1 (30%); 16 were T2 (53%); 4 were T3 (13%); and 1 was T4a (3%). The anatomic sites of these primary tumors were tonsil in 14 (47%), tongue base in 9 (30%), glossotonsillar sulcus in 3 (10%), soft palate in 3 (10%), and oropharyngeal wall in 1 (3%). There was only 1 patient (3%) who had a positive margin after primary resection; further resection achieved a final negative margin. Perineural invasion was noted in 3 tumors (10%). No patient received postoperative adjuvant therapy. At a mean follow-up of 2.7 years (range, 1.5-5.1 years), there was 1 patient with local failure (3%)., Conclusion: As the only modality used for treatment of pathologically low-risk OSCCs, TORS provides high local control and is associated with low surgical morbidity.

Objective: To evaluate changes in patient-perceived swallowing function over time following transoral robotic surgery (TORS) for primary T1 and T2 oropharyngeal squamous cell carcinomas., Design: Prospective case series., Setting: Academic tertiary referral center., Patients: Forty-two patients with T1 or T2 oropharyngeal squamous cell carcinomas., Intervention: TORS-assisted resection of indicated tumors., Main Outcome Measures: Changes in patient-perceived swallowing function over time (using the M. D. Anderson Dysphagia Inventory) and gastrostomy tube dependence., Results: Between March 19, 2007, and April 21, 2010, forty-two patients with primary T1 or T2 oropharyngeal squamous cell carcinomas underwent TORS-assisted resection. Most (76% [32 of 42]) patients had stage III disease; 93% (39 of 42) of patients underwent staged neck dissection. The median postoperative follow-up time was 17 months (range, 4-40 months). There were no complications or tumor recurrences. Postoperative chemotherapy use predicted gastrostomy tube retention for longer than 3 months (P = .01). Immediate mean postoperative M. D. Anderson Dysphagia Inventory scores in each assessed domain (global, emotional, physical, and functional) decreased compared with preoperative baseline scores; however, ongoing improvement in all domains was observed over time. Nodal status (P = .049), follow-up time of less than 12 months (P = .03), and preoperative physical scores of less than 100 (P = .01) predicted poorer physical M. D. Anderson Dysphagia Inventory outcomes. Positive pathological margins predicted poorer functional scores (P = .03)., Conclusions: After TORS-assisted resection of T1 and T2 oropharyngeal squamous cell carcinomas, approximately one-third of patients will experience a sustained decrease in perceived swallowing function. However, ongoing improvement of swallowing function over time is likely even after 12 months. Patients receiving adjuvant chemotherapy after TORS should be counseled about the possibility of prolonged gastrostomy tube dependence.

Background: Oropharyngeal squamous cell carcinomas (OSCCs) are associated with high-grade human papillomavirus (HPV) infection in 20% to 30% of cases. HPV-16 DNA has been detected in cervical lymph node metastases of HPV-16(+) OSCC. However, the meaning of HPV-16 DNA detection in lymph nodes remains controversial. Does the presence of HPV-16 DNA in lymph nodes correlate with their metastatic involvement, or is it just a consequence of the filter function of lymph nodes?, Methods: Viral load quantification using reverse transcriptase-polymerase chain reaction was retrospectively performed in primary tumors and in cervical lymph nodes, originating from levels IIa, IIb, and III, in 11 patients with HPV-16(+) OSCC and in 3 control patients with HPV-16(-) OSCC., Results: A total of 45 lymph node levels were analyzed. HPV-16 DNA was not detected in HPV-16(-) OSCC lymph nodes. No statistically significant difference was found between primary tumors and metastatic lymph nodes viral load (P > .01). The viral load value was significantly higher in metastatic lymph nodes than in tumor-free lymph nodes (P < .01). Among 27 tumor-free lymph node levels, the viral load value was undetectable in 16, low or medium (<10(5) copies per million cells) in 8, and high (>10(5) copies per million cells) in 3., Conclusions: HPV-16 DNA detection in lymph nodes of patients affected with HPV-16(+) oropharyngeal cancer is indicative of metastatic involvement. Tumor-free lymph nodes with a high viral load value would suggest the presence of occult lymph nodes metastasis and the opportunity to use HPV-16 DNA as a metastatic marker. Further investigations are needed.

Objectives: To determine the oncologic and functional outcomes in patients undergoing primary transoral robotic surgery followed by adjuvant therapy as indicated with a minimum of 18-month follow-up for advanced oropharyngeal carcinoma., Design: Prospective single-center cohort study., Setting: Academic university health system and tertiary referral center., Patients: Forty-seven adults with newly diagnosed and previously untreated advanced oropharyngeal carcinoma., Intervention: Transoral robotic surgery with staged neck dissection and adjuvant therapy as indicated., Main Outcome Measures: Margin status, recurrence, disease-specific and disease-free survival, gastrostomy tube dependence, and safety and efficacy end points., Results: In the 47 patients enrolled with stages III and IV advanced oropharyngeal carcinoma, mean follow-up was 26.6 months. There was no intraoperative or postoperative mortality. Resection margins were positive in 1 patient (2%). At last follow-up, local recurrence was identified in 1 patient (2%), regional recurrence in 2 (4%), and distant recurrence in 4 (9%). Disease-specific survival was 98% (45 of 46 patients) at 1 year and 90% (27 of 30 patients) at 2 years. Based on pathologic risk stratification, 18 of 47 patients (38%) avoided chemotherapy, and 5 patients (11%) did not receive adjuvant radiotherapy and concurrent chemotherapy in their treatment regimen. At minimum follow-up of 1 year, only 1 patient required a gastrostomy tube., Conclusions: This novel transoral robotic surgery treatment regimen offers disease control, survival, and safety commensurate with standard treatments and an unexpected beneficial outcome of gastrostomy dependency rates that are markedly lower than those reported with standard nonsurgical therapies.

Objective: To determine the feasibility of robotic-assisted salvage surgery for oropharyngeal cancer., Design: Retrospective case-controlled study., Setting: Academic, tertiary referral center., Patients: Patients who underwent surgical resection for T1 and T2 oropharyngeal cancer between 2001 and 2008 were classified into the following 3 groups based on type of resection: (1) robotic-assisted surgery for primary neoplasms (robotic primary) (n = 15), (2) robotic-assisted salvage surgery for recurrent disease (robotic salvage) (n = 7), and (3) open salvage resection for recurrent disease (n = 14)., Main Outcome Measures: Data regarding tumor subsite, stage, and prior treatment were evaluated as well as margin status, nodal disease, length of hospital stay, diet, and tracheotomy tube dependence., Results: The median length of stay in the open salvage group was longer (8.2 days) than robotic salvage (5.0 days) (P = .14) and robotic primary (1.5 days) resection groups (P < .001). There was no difference in postoperative diet between robotic primary and robotic salvage surgery groups. However, a greater proportion of patients who underwent open salvage procedures were gastrostomy tube dependent 6 months following treatment (43%) compared with robotic salvage resection (0%) (P = .06). A greater proportion of patients who underwent open salvage procedures also remained tracheotomy tube dependent after 6 months (7%) compared with robotic salvage or robotic primary patients (0%) (P = .48). No complications were reported in the robotic salvage group. Two patients who underwent open salvage resection developed postoperative hematomas and 2 developed wound infections., Conclusion: When feasible, robotic-assisted surgery is an acceptable procedure for resection of both primary and recurrent oropharyngeal tumors. Trial Registration clinicaltrials.gov Identifier: NCT00473564.

Objective: To demonstrate the role of transoral laser microsurgery (TLM) in the treatment of oropharyngeal cancer., Design: A 2-center retrospective case series analysis., Setting: Two tertiary care medical centers., Patients: The study population comprised 69 patients with previously untreated select T1 to T3, N0 to N2 squamous cell carcinoma of the oropharynx, of whom 44 (74%) had no indication for adjuvant RT and 25 (36%) had an indication for adjuvant RT to the neck alone but declined radiotherapy. The primary tumor sites were the tonsil (n = 28 [41%]), tongue base (n = 28 [41%]), pharyngeal wall (n = 8 [12%]), soft palate (n = 4 [6%]), and vallecula (n = 1 [1%])., Interventions: Transoral laser microsurgery in 69 patients, with neck dissection in 59 patients (83%)., Main Outcome Measures: Complications, local and regional control, overall and disease-specific survival, swallow function, and feeding tube dependence., Results: Over the mean follow-up period of 44 months, 66 of 69 patients had no disease recurrence at the primary site. The 5-year local control estimate was 94%. The mean duration of hospitalization was 3 days. There were no major complications relating to TLM. No patient required a permanent feeding or tracheostomy tube. For stage I, II, and III disease, the 5-year Kaplan-Meier estimates of locoregional control were 90%, 73%, and 70%, respectively. The 5-year overall survival estimate was 86%., Conclusions: Transoral laser microsurgery alone with or without neck dissection is an effective approach for select T1 to T3, N0, or N1 oropharyngeal cancer. Low levels of morbidity, short treatment duration, and excellent disease control make it an attractive therapeutic strategy. The treatment option of endoscopic-assisted laser microsurgery should be discussed by the multidisciplinary team for patients presenting with tumors suitable for this approach.

Objective: To determine if oropharyngoplasty using a Gehanno technique of superior constrictor velopharyngoplasty, base of tongue mounding, and primary hypopharyngeal closure in combination with template-based revascularized free tissue transfer is effective for reconstruction of the oropharyngeal defect., Design: Prospective case series., Setting: Tertiary care academic medical center., Patients: The study population comprised 25 patients (21 men and 4 women; mean age, 55.3 years) presenting from January 1998 to January 2001 with oropharyngeal squamous cell carcinoma. A comparison was performed based on the percentage of resection of the soft palate (group 1, < or =50% palate; group 2, >50% palate)., Interventions: Of the 25 patients, 24 (96%) received radiotherapy. The donor sites were radial forearm for 23 of 25 patients (92%) and lateral arm for 2 of 25 patients (8%). The mean area was 92 cm(2) (range, 25-150 cm(2)), and the mean length of the velopharyngoplasty component of the oropharyngoplasty was 2.15 cm (range, 1-3 cm)., Main Outcome Measures: Gastrostomy tube dependence, major and minor complications, time to oral intake, speech and swallowing assessment, and quality-of-life assessment., Results: Of the 25 patients, 2 (8%) remain gastrostomy dependent; 6 (24%) developed major complications; and 7 (28%) developed minor complications. Speech in both groups 1 and 2 was considered understandable most of the time, with occasional repetition. The group 1 patient with a median assessment score could eat a solid diet without restriction of place or person, whereas the group 2 patient with a median assessment score could eat a soft, moist diet with selected persons in selected places., Conclusion: Integration of oropharyngoplasty with template-based revascularized free tissue transfer produced speech results that were independent of palate defect size, and swallow function test results were similar to other published reconstructive techniques.

Objectives: To assess the prevalence of speech and swallowing impairment after radical surgery for oral and oropharyngeal cancer from the patient's viewpoint and to examine the association of these functional alterations with selected clinical characteristics regarding patients, tumors, and oncologic treatment., Design: Cross-sectional, multicenter study using a self-administered questionnaire., Setting: Forty-three hospitals in Germany, Switzerland, and Austria., Patients: A total of 3894 questionnaires about rehabilitation problems after treatment for oral and oropharyngeal squamous cell carcinoma were sent to patients. Of these, 1652 were filled out and returned, and 1334 (80.8%) met the inclusion criteria., Main Outcome Measures: Morbidity associated with treatment of oral and oropharyngeal cancer., Results: Speech problems were reported by 851 patients (63.8%), and swallowing problems were reported by 1006 patients (75.4%). The variables that presented a significant association with speech and swallowing impairment were sex, tumor location, pTNM stages, stage of tumor, treatment modality, and reconstruction type., Conclusions: This survey, based on patient perception, suggests that those who undergo radiotherapy associated with the surgical removal of a tumor, have late-stage tumors (III-IV), or have tumors located in the floor of the mouth should be informed of the greater risk of persistent severe speech and swallowing problems.

Objective: To determine risk factors predicting early postoperative aspiration in patients after microvascular free flap reconstruction of oral cavity and oropharyngeal defects., Design: Retrospective analysis., Setting: Academic tertiary care referral medical center., Patients: The study included 100 patients who underwent resection of oral cavity or oropharyngeal tumors with immediate free flap reconstruction of the defect., Main Outcome Measures: Dysphagia severity was assessed by modified barium swallow study performed within 90 days after surgery to determine the presence or absence of tracheal aspiration. Aspiration risk factors analyzed included age; sex; tumor T and N stage; comorbidity level (American Society of Anesthesiologists classification); preoperative swallowing function; history of tobacco use; surgical approach used for tumor resection; defect classification; type of free flap; history of radiation therapy, surgery, and/or chemotherapy; and surgical defect classification., Results: The following risk factors were significant predictors of postoperative aspiration on univariate analysis: prior radiation therapy (P < .001), tongue base resection classification (P = .001), tumor N stage (P < .001), hypoglossal nerve sacrifice (P = .004), and presence of a mandibular osteotomy (P = .01). On multivariate analysis, only a history of radiation therapy (P = .002) and tongue base resection (P = .008) remained statistically significant predictors of aspiration., Conclusion: Patients with resection of more than half of the tongue base and patients with a history of radiation therapy are at high risk of having early postoperative aspiration after free flap reconstruction.

Objective: To analyze the prognostic effect of epidermal growth factor receptor (EGFR), matrix metalloproteinases 2 and 9, and vascular endothelial growth factor expression in patients with locally recurrent oral carcinoma after salvage surgery., Design: Retrospective cohort study. Settings Tertiary center cancer hospital., Patients: The charts of 111 patients with local recurrence of oral carcinomas were retrospectively analyzed. The previous treatment consisted of surgery in 33 patients (30.0%), radiotherapy with or without chemotherapy in 46 patients (41.0%), and surgery with adjuvant radiotherapy in 32 patients (29.0%). The expression of EGFR, matrix metalloproteinases 2 and 9, and vascular endothelial growth factor was analyzed with a tissue microarray immunohistochemical technique., Main Outcome Measures: Overall survival and cancer-specific survival (CSS)., Results: The recurrences were diagnosed in less than 1 year in 69 patients (62.2%) and in more than 1 year in 42 patients (37.8%). The prognosis was worse in the group with the disease-free interval of less than 1 year (P = .01). Patients with more advanced disease (clinical stage of recurrence, III/IV) had worse rates of CSS (P = .04). Cases that were positive for EGFR had a 3-year CSS of 27.2%, while EGFR-negative cases had a 3-year CSS of 64.3% (P = .001). The expression of matrix metalloproteinases 2 (P = .83) and 9 (P = .15) and vascular endothelial growth factor (P = .86) was not significant in this group. In multivariate analysis, only the disease-free interval and the overexpression of EGFR were associated with a higher risk of cancer death., Conclusions: Local recurrence in oral carcinomas carries a poor prognosis. A disease-free interval of more than 1 year and a EGFR-negative expression are the main prognostic factors related to better CSS in patients treated with salvage surgery.

Objectives: To assess the feasibility of sentinel lymph node (SLN) localization and to determine the predictive value of SLN biopsy for occult neck metastases in patients previously treated with surgery or radiation therapy and with N0 squamous cell carcinoma of the oral cavity or oropharynx., Design: Prospective case series., Setting: Tertiary academic hospital., Patients: Eleven patients with T1 to T4 N0 squamous cell carcinoma of the oral cavity or oropharynx., Interventions: Patients underwent preoperative peritumoral injection of technetium Tc 99m sulfur colloid followed by dynamic lymphoscintigraphy and operative localization of the SLN(s) with the use of a handheld gamma probe., Main Outcome Measures: The presence or absence of metastatic disease in N0 squamous cell carcinoma of the oral cavity and oropharynx in patients previously treated with surgery or radiation therapy as identified by SLN biopsy findings., Results: In each of the 11 patients, 1 to 3 SLNs were identified by lymphoscintigraphy. All SLNs identified by lymphoscintigraphy were successfully identified and removed with the use of an intraoperative gamma probe. In 10 of the 11 patients, the biopsy findings from the SLN(s) accurately predicted the presence or absence of occult neck metastasis. There was 1 instance of a negative SLN with a positive neck dissection. The overall negative predictive value of the study was 91%. No aberrant lymphatic drainage patterns were observed in this study., Conclusion: In patients previously treated with surgery or radiation therapy, SLN biopsy was as effective as in previously untreated patients according to published reports and warrants inclusion of this patient group into larger studies.