Early-stage Oropharyngeal Squamous Cell Carcinoma Research Articles

Outcomes of transoral robotic surgery for early-stage oropharyngeal squamous cell carcinoma with low rates of adjuvant therapy: A consecutive single-institution study from 2013 to 2020

IntroductionThe incidence of oropharyngeal squamous cell carcinoma (OPSCC) has increased in recent decades, driven by infection with human papillomavirus (HPV). Transoral robotic surgery (TORS) and neck dissection (ND) has been employed as an alternative to radiotherapy/chemoradiotherapy. The current literature is lacking studies providing an exhaustive overview of recurrence characteristics and long-term outcomes in TORS-treated OPSCC-patients. MethodsAll patients treated for OPSCC with primary TORS + ND in Eastern Denmark between 2013 and 2020 were included in the study. The aim was to explore overall survival (OS), recurrence-free survival (RFS), recurrence patterns, and ultimate failure rate (UFR). OS and RFS were examined using the Kaplan-Meier method. Cox proportional regression analyses were employed to examine effect of different variables on risk of death and recurrence. ResultsThe study included 153 patients of which 88.9 % (n = 136) were treated with TORS alone while 11.1 % (n = 17) received adjuvant therapy. The 1-, 3-, and 5-year OS were 97.4 %, 94.1 %, and 87.6 % while 1-, 3-, and 5-year RFS were 96.6 %, 87.8 %, and 84.9 %. The UFR was 6.5 % in the cohort. Patients with HPV+/p16 + OPSCC had a significantly better 5-year OS of 92.3 % than patients with discordant or double-negative HPV/p16 status (OS = 73.3 %). No differences in outcomes between patients treated with or without adjuvant therapy were found in regression analysis. ConclusionExcellent survival and disease control was obtained with TORS + ND in this cohort, despite lesser application of adjuvant therapy than other TORS-centers, implying that TORS without adjuvant therapy can be successfully applied in treatment of early-stage OPSCC.

Geographical Disparities in the Management of Early-Stage Oropharyngeal Squamous Cell Carcinoma (OPSCC) in the United States (US)

Geographical Disparities in the Management of Early-Stage Oropharyngeal Squamous Cell Carcinoma (OPSCC) in the United States (US)

Altered microheterogeneity at several N-glycosylation sites in OPSCC in constant protein expression conditions.

Protein glycosylation responds sensitively to disease states. It is implicated in every hallmark of cancer and has recently started to be considered as a hallmark itself. Changes in N-glycosylation microheterogeneity are more dramatic than those of protein expression due to the non-template nature of protein glycosylation. This enables their potential use in serum-based diagnostics. Here, we perform glycopeptidomics on serum from patients with oropharyngeal squamous cell carcinoma (OPSCC), compared to controls and comparing between cancers based on etiology (human papilloma virus- positive or negative). Using MS2, we then targeted glycoforms, significantly different between the groups, to identify their glycopeptide compositions. Simultaneously we investigate the same serum proteins, comparing whether N-glycosylation changes reflect protein-level changes. Significant glycoforms were identified from proteins such as alpha-1-antitrypsin (SERPINA1), haptoglobin, and different immunoglobulins. SERPINA1 had glycovariance at 2 N-glycosylation sites, that were up to 35 times more abundant in even early-stage OPSCCs, despite minimal differences between SERPINA1 protein levels between groups. Some identified glycoforms' fold changes (FCs) were in line with serum protein level FCs, others were less abundant in early-stage cancers but with great variance in higher-stage cancers, such as on immunoglobulin heavy constant gamma 2, despite no change in protein levels. Such findings indicate that glycovariant analysis might be more beneficial than proteomic analysis, which is yet to be fruitful in the search for biomarkers. Highly sensitive glycopeptide changes could potentially be used in the future for cancer screening. Additionally, characterizing the glycopeptide changes in OPSCC is valuable in the search for potential therapeutic targets.

Decisional regret, symptom burden, and quality of life following transoral robotic surgery for oropharyngeal cancer

BackgroundTransoral robotic surgery (TORS) has equivalent oncologic control to radiotherapy with potential for improved quality of life (QOL) and lower patient-reported decisional regret. MethodsCross-sectional study between 2016 and 2021 of TORS patients with early-stage oropharyngeal squamous cell carcinoma who completed the Decision Regret Scale (DRS), M. D. Anderson Dysphagia Inventory (MDADI), and University of Washington Quality of Life (UW-QOL). The median time from treatment to questionnaire completion was 1.8 years (IQR 1.4–3.3, range 1.0–5.6). ResultsOf 65 patients, 84.6% expressed no or mild decisional regret. Regret was not associated with clinical parameters or adjuvant treatment but was correlated with MDADI (τavg = −0.23, p < 0.001) and UW-QOL (τavg = −0.27, p < 0.001). Worse MDADI was associated with older age and worse UW-QOL was associated with multi-site operation and shorter time to survey. ConclusionsOverall, the TORS cohort expressed very limited decisional regret. DRS scores were unaffected by clinicodemographics or additional adjuvant therapies, but decision regret was correlated with worse QOL and worse swallowing.

Presentation and outcomes of patients with clinically T1-2, N0 oropharynx squamous cell carcinoma: The interplay of primary treatment modality and human papillomavirus status.

To examine the pattern of utilization and outcomes of definitive radiotherapy (RT) versus primary robotic-assisted surgery in patients with early-stage oropharyngeal squamous cell carcinoma (OPSCC). A retrospective cohort analysis of patients with clinically T1-2, N0 OPSCC was performed using the National Cancer Database, 2010-2016. A total of 1451 patients were included. Prevalence of human papillomavirus (HPV)-positive tumors was 58.30%. Primary surgery was performed in 30.25% of the sample. Tongue base and clinically T1 tumors were each associated with a higher likelihood of undergoing surgery (p < 0.05). Histopathology of patients who underwent surgery demonstrated a prevalence of 15.95% with lymphovascular invasion, 16.67% with extranodal extension, 19.36% were T updated, and 30.00% were N upstaged. Improved survival was observed in the surgery + adjuvant RT group compared to RT alone for HPV-positive tumors (HR: 0.27; 95%CI: 0.12, 0.62; p=0.002). This study provides epidemiological perspective regarding management pattern and outcomes of patients with early-stage OPSCC.

Factors Predictive of Primary Therapeutic Modality in Early-Stage Oropharyngeal Squamous Cell Carcinoma

<h3>Purpose/Objective(s)</h3> Traditionally, definitive radiotherapy (RT) was the preferred treatment for oropharyngeal squamous cell carcinoma (OPSCC). Changes in both surgical technology (the advent of transoral robotic surgery) and the pathogenesis of the disease (increase in patients with HPV-associated disease) have altered this paradigm. We aimed to assess factors influencing the use of definitive surgery versus RT among patients with early stage OPSCC. <h3>Materials/Methods</h3> We used the Surveillance, Epidemiology, and End Results (SEER) Head and Neck with HPV Status Database along with the SEER Census Tract-level Socioeconomic Status (SES) and Rurality Database. From 40,787 patients treated from 2010 – 2016, we identified 9,292 who met inclusion criteria (T0-3, N0-2, M0 disease with known status for all variables included in our model). Patients undergoing pharyngectomy were deemed to have definitive surgery. Those receiving RT in the absence of a pharyngectomy were deemed to have definitive RT. We performed a multivariable logistic regression for factors correlated with definitive RT. Our model initially included age and year of diagnosis, gender, race, primary site, T- and N-classification, HPV status, marital status, rural/urban status, and socioeconomic status (SES) as indicated by Yost index. We used a backwards stepwise selection algorithm until no variable had a p value > 0.10; the final model included all variables except gender, race, and year of diagnosis. <h3>Results</h3> 6,008 patients (64.7%) received definitive RT and 3,284 (35.3%) received definitive surgery. Of those receiving definitive surgery, 2,510 (76.4%) also received RT. On multivariable logistic regression, higher T- or N-classification and non-tonsillar fossa primary site significantly increased the likelihood of definitive RT. Patients with HPV-positive disease were less likely to receive definitive RT (odds ratio (OR) = 0.87, 95% CI 0.77 – 0.98, p = 0.021). Patients in entirely rural census tracts were less likely to receive definitive RT (OR = 0.81, 95% CI 0.67 – 0.99, p = 0.042). Those living in census tracts in the lowest SES tertile were more likely to receive definitive RT (OR = 1.17, 95% CI 1.02 – 1.33, p = 0.014). <h3>Conclusion</h3> We identified sociodemographic and clinical factors associated with primary treatment for early stage OPSCC. Tumor size and primary site, appear to influence treatment allocation; however, non-clinical factors may also play a role. Patients living in rural areas are more likely to receive definitive surgery; patients in lower SES areas are more likely to receive definitive RT. Further investigation into these differences is warranted to ensure equal access to all therapeutic options for patients with early stage OPSCC.

Randomized Trial of Radiotherapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Long-Term Results of the ORATOR Trial.

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has risen rapidly, because of an epidemic of human papillomavirus infection. The optimal management of early-stage OPSCC with surgery or radiation continues to be a clinical controversy. Long-term randomized data comparing these paradigms are lacking. We randomly assigned patients with T1-T2, N0-2 (≤ 4 cm) OPSCC to radiotherapy (RT) (with chemotherapy if N1-2) versus transoral robotic surgery plus neck dissection (TORS + ND) (with or without adjuvant therapy). The primary end point was swallowing quality of life (QOL) at 1-year using the MD Anderson Dysphagia Inventory. Secondary end points included adverse events, other QOL outcomes, overall survival, and progression-free survival. All analyses were intention-to-treat. Herein, we present long-term outcomes from the trial. Sixty-eight patients were randomly assigned (n = 34 per arm) between August 10, 2012, and June 9, 2017. Median follow-up was 45 months. Longitudinal MD Anderson Dysphagia Inventory analyses demonstrated statistical superiority of RT arm over time (P = .049), although the differences beyond 1 year were of smaller magnitude than at the 1-year timepoint (year 2: 86.0 ± 13.5 in the RT arm v 84.8 ± 12.5 in the TORS + ND arm, P = .74; year 3: 88.9 ± 11.3 v 83.3 ± 13.9, P = .12). These differences did not meet the threshold to qualify as a clinically meaningful change at any timepoint. Certain differences in QOL concerns including more pain and dental concerns in the TORS + ND arm seen at 1 year resolved at 2 and 3 years; however, TORS patients started to use more nutritional supplements at 3 years (P = .015). Dry mouth scores were higher in RT patients over time (P = .041). On longitudinal analysis, the swallowing QOL difference between primary RT and TORS + ND approaches persists but decreases over time. Patients with OPSCC should be informed about the pros and cons of both treatment options (ClinicalTrials.gov identifier: NCT01590355).

Perioperative Mortality Risk in Patients Undergoing Transoral Robotic Surgery for T1-T2 Oropharyngeal Squamous Cell Carcinoma: A National Cancer Database Study.

The National Cancer Database is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical methods used or for the conclusions drawn from these data by the investigators.IntroductionTransoral robotic surgery (TORS) is well established as initial definitive treatment for early-stage oropharyngeal squamous cell carcinoma (OPSCC) as an alternative to radiation therapy with similar survival rates. While proponents of TORS focus on the reduced morbidity of treatment compared to open procedures, shortened hospital admissions and equivalent survival outcomes to non-surgical treatment, there remain concerns over the risk of mortality within the acute perioperative period. Therefore, we sought to determine the 30-day and 90-day perioperative mortality risk using the National Cancer Database.MethodsA retrospective cohort analysis was performed for patients diagnosed with pathologic T1/2 OPSCC between January 1, 2010, and December 31, 2016 that underwent primary surgical treatment with TORS and was not restricted by HPV status. The primary outcome was 30-day perioperative mortality. The secondary outcome was 90-day perioperative mortality. Univariable analysis was used to identify variables associated with 30-day perioperative mortality.ResultsIn total, 4,127 patients (mean [SD; range] age, 59 [9.5; 22-90] years; 3,476 [84%] men and 651 [16%] women) met inclusion criteria. The number of patients with pT1-2 OPSCC undergoing TORS increased three-fold between 2010 (279/4,127; 7%) to 2016 (852/4,127; 21%). The overall 30-day and 90-day perioperative mortality rate for TORS during the study period was 0.6% (23/4,127) and 0.9% (38/4,127), respectively. On univariable analysis (UVA), age≥65 was the only predictor of 30-day perioperative mortality (OR 3.41; 95% CI 1.49-7.81).ConclusionThe overall risk of all cause mortality following TORS for early-stage OPSCC remains low. The risk of mortality is higher in elderly patients and should be considered, in addition to previously established risk factors, during patient selection and counselling.

Evaluating contralateral neck failure in patients with lateralized OPSCC treated with transoral robotic surgery and neck management based on pre-operative SPECT-CT lymphatic mapping

BackgroundRisk of contralateral nodal metastases in oropharyngeal squamous cell carcinoma (OPSCC) is relatively low, however, many OPSCC patients receive bilateral neck treatment. This study evaluates the oncological outcomes with management of the contralateral cN0 neck based on lymphatic mapping with single photon emission computed tomography (SPECT-CT).MethodsRetrospective evaluation of patients with lateralized cT1-2 and contralateral cN0 OPSCC treated with primary surgery between December 2017 and October 2019. All patients underwent pre-operative lymphatic mapping using SPECT-CT. Clinical parameters including demographics, tumor characteristics and oncological outcomes were recorded.ResultsThirteen patients underwent primary site resection with transoral robotic surgery (TORS) and ipsilateral neck dissection with or without adjuvant therapy. Twelve patients (92.3%) had ipsilateral drainage on SPECT-CT, whereas 1 (7.7%) patient had bilateral neck lymphatic drainage. Four patients (30.8%) underwent post-operative radiation therapy (PORT). Three patients with unilateral drainage on SPECT-CT underwent PORT with unilateral neck irradiation, and 1 patient with bilateral drainage underwent PORT with bilateral neck irradiation. Seven (53.8%) patients were staged as pT1, 6 (46.2%) patients as pT2, 6 (46.2%) patients were pN0, 3 (23.1%) patients were pN1, 1 (7.7%) patient was pN2a for and 3 (23.1%) patients were N2b. The median distance of the tumor from midline was 1.05 cm (0.0–1.58). Primary sites included tonsil (n = 10, 76.9%) and tongue base (n = 3, 23.1%). The median follow-up time was 15.4 months. All patients were disease free at the latest follow-up with no contralateral neck failures.ConclusionsPre-operative mapping of lymphatic drainage in early stage OPSCC with SPECT-CT is a promising tool which can reduce treatment to the contralateral neck potentially without compromising oncological outcomes.Graphical

Long-term survival outcomes after primary transoral robotic surgery (TORS) with concurrent neck dissection for early-stage oropharyngeal squamous cell carcinoma

Background In 2013, transoral robotic surgery (TORS) was implemented as a protocolled treatment alternative to the traditional radiotherapy (RT) in Denmark for oropharyngeal squamous cell carcinoma (OPSCC). In 2017, we published our first prospective feasibility study, showing that TORS with concurrent neck dissection successfully achieved negative margins in 29 out of 30 patients (97%) with early-stage OPSCC. Aims/objectives This follow-up study aims to evaluate the five-year overall survival (OS), disease-specific survival (DSS) and recurrence-free survival (RFS). Methods Retrospective follow-up study including 30 patients treated with TORS for early-stage OPSCC (T1–T2, N0–N1, M0, UICC 7th edition) from September 2014 to January 2016 at a single head and neck cancer centre in Denmark. The five-year OS, DSS and RFS, including a detailed analysis of the recurrences, were addressed. Results The five-year OS, DSS and RFS was 90%, 93% and 87%, respectively. Median follow-up was 54.5 months. Four patients developed a recurrence, with one regional, one distant metastatic (M) and two locoregional recurrences. The median time to recurrence was 24 months (range 3–42 months). Conclusions and significance This follow-up study demonstrates good five-year OS, DSS and RFS in a prospective cohort of patients undergoing TORS and neck dissection for early-stage OPSCC.

Feeding Tube Placement Following Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma.

To identify factors that may predict the need for feeding tubes in patients undergoing transoral robotic surgery (TORS) in the perioperative setting. Retrospective chart review. Academic tertiary center. A retrospective series of patients undergoing TORS for oropharyngeal squamous cell carcinoma (OPSCC) was identified between October 2016 and November 2019 at a single tertiary academic center. Patient data were gathered, such as frailty information, tumor characteristics, and treatment, including need for adjuvant therapy. Multiple logistic regression was performed to identify factors associated with feeding tube placement following TORS. A total of 138 patients were included in the study. The mean age was 60.2 years (range, 37-88 years) and 81.9% were male. Overall 82.9% of patients had human papilloma virus-associated tumors, while 28.3% were current or former smokers with a smoking history ≥10 pack-years. Eleven patients (8.0%) had a nasogastric or gastrostomy tube placed at some point during their treatment. Five patients (3.6%) had feeding tubes placed perioperatively (<4 weeks after TORS), of which 3 were nasogastric tubes. Six patients (4.3%) had feeding tubes placed in the periadjuvant treatment setting for multifactorial reasons; 5 of which were gastrostomy tubes. Only 1 patient (0.7%) was gastrostomy dependent 1 year after surgery. Multiple logistic regression did not demonstrate any significant predictive variables affecting perioperative feeding tube placement following TORS for OPSCC. Feeding tubes are seldom required after TORS for early-stage OPSCC. With appropriate multidisciplinary planning and care, patients may reliably avoid the need for feeding tube placement following TORS for OPSCC.

Cohort profile: indigenous human papillomavirus and oropharyngeal squamous cell carcinoma study - a prospective longitudinal cohort

PurposeOur aims are to: (1) estimate prevalence, incidence, clearance and persistence of oral human papillomavirus (HPV) infection among Indigenous Australians; (2) identify risk factors associated with oropharyngeal squamous cell carcinoma...

Treatment outcomes of transoral robotic and non-robotic surgeries to treat oropharyngeal, hypopharyngeal, and supraglottic squamous cell carcinoma: A multi-center retrospective observational study in Japan

ObjectivesThe aim of this multicenter retrospective cohort study was to compare efficacy and subsequent postoperative treatment between transoral robotic surgery (TORS) and any non-robotic transoral surgery in Japanese patients with early oropharyngeal squamous cell carcinoma (OPSCC), hypopharyngeal SCC (HPSCC), or supraglottic SCC (SGSCC). Materials and methodsClinical information and surgical outcomes were compared between patients with early-stage OPSCC, HPSCC, and SGSCC who underwent TORS (TORS cohort) and those who underwent non-robotic transoral surgery, including transoral videolaryngoscopic surgery (TOVS), endoscopic laryngopharyngeal surgery (ELPS), and transoral laser microsurgery (TLM) (non-robotic cohort). The data of the Head and Neck Cancer Registry of Japan (registry cohort) were used to validate the comparison. The main outcomes were the presence of positive margins under pathology and the requirement for postoperative therapy, including radiotherapy or chemoradiotherapy. ResultsSixty-eight patients in the TORS cohort, 236 patients in the non-robotic cohort, and 1,228 patients in the registry cohort were eligible for this study. Patients in the TORS cohort were more likely to have oropharyngeal tumor disease and T2/3 disease than those in the other cohorts (P<0.001 and P=0.052, respectively). The TORS cohort had significantly fewer patients with positive surgical margins than the non-robotic cohort (P=0.018), as well as fewer patients who underwent postoperative treatment, although the difference was not significant (P=0.069). In the subgroup analysis of patients with OPSCC, a total of 57 patients in the TORS cohort, 73 in the non-robotic cohort, and 171 in the registry cohort were eligible for the present study. Patients with OPSCC who underwent TORS were more likely to have lateral wall lesions than those in the other cohorts (P=0.003). The TORS cohort also had significantly fewer patients with positive surgical margins than the non-robotic cohort (P=0.026), and no patients in the TORS cohort underwent any postoperative treatment for OPSCC, although the difference was not significant (P=0.177). ConclusionsOur results suggest that TORS leads to fewer positive surgical margins than non-robotic transoral surgeries. The clinical significance of TORS may be further validated through the results of all-case surveillance for patients who underwent TORS running in Japan in the future.

Survival Impact of Transoral Robotic Surgery in Early-Stage Oropharyngeal Cancer

Transoral robotic surgery (TORS) has multiple theoretical advantages over conventional surgery for early-stage oropharyngeal squamous cell carcinoma (OPSCC). Since FDA-approval in December 2009, TORS has become a standard of care treatment for early-stage OPSCC, but there is limited data comparing TORS to conventional surgery with respect to peri-operative mortality, surgical outcomes, and long-term oncologic outcomes. To this end, we examined the patterns of uptake of TORS and its impact on surgical outcomes and survival using real-world data from a large national cancer registry. Patients with T1-2 OPSCC undergoing definitive surgery from 2010 to 2015 were identified in the National Cancer Database. Univariate and multivariate Cox regression models were constructed to evaluate the association between TORS and survival, adjusting for patient- and disease-related covariates. Survival with robotic and non-robotic surgery was also compared in three unrelated disease sites where both approaches are widely employed: Gleason 7-10 prostate cancer, stage I endometrial cancer, and stage IA2 or IB1 cervical cancer, to assess for systemic selection bias regarding surgical approach in national registry data. Of the 9,745 patients who met inclusion criteria, 2,694 (27.6%) underwent TORS. There was a significant increase in the utilization of TORS, from 18.3% to 35.5% of all surgeries for T1-2 OPSCC from 2010 to 2015 (P = 0.003). TORS was associated with similar 90-day peri-operative mortality as conventional surgery (1.4% vs. 1.0%, P = 0.11) and length of hospital stay (4.28 days vs 4.42 days, P = 0.49). In terms of surgical outcomes, TORS was associated with lower rates of positive surgical margins (12.5% vs 20.3%, P<0.001), and accordingly lower utilization of adjuvant chemoradiation (28.6% vs. 35.7%, P<0.001). In the subset of 4,071 patients with known HPV-status, TORS was associated with improved overall survival (OS) compared to non-robotic surgery in multivariable Cox regression (hazard ratio [HR], 0.747; 95% CI, 0.612-0.913, P = 0.004), even when excluding facilities that did not offer TORS. 5-year OS was 84.8% vs. 80.3% among patients undergoing TORS versus non-robotic surgery in propensity score-matched cohorts (P<0.001). By contrast, robotic surgery was not associated with improved OS in other cancers, such as prostate (HR 0.893; 95% CI 0.772-1.032; P = 0.13), endometrial (HR 0.948; 95% CI 0.879-1.022; P = 0.16), and cervical cancer (HR 1.282; 95% CI 0.943-1.743, P = 0.11). The utilization of TORS has rapidly increased during the first 6 years of adoption. TORS was associated with higher rates of margin negative surgery and improved OS compared to non-robotic surgery in early-stage OPSCC. The association between improved OS and robotic surgery was unique to early-stage OPSCC, and was not observed in prostate, endometrial or cervical cancer. It is unclear if these results are due to technical differences, surgical acumen, or other factors.

Comparison of Survival After Transoral Robotic Surgery vs Nonrobotic Surgery in Patients With Early-Stage Oropharyngeal Squamous Cell Carcinoma

Transoral robotic surgery has been widely adopted since approval by the US Food and Drug Administration in December 2009, despite limited comparative data. To compare the long-term outcomes of transoral robotic surgery with those of nonrobotic surgery for patients with early-stage oropharyngeal cancer. 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. Overall survival. 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). 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.

Transoral robotic surgery: a 4-year learning experience in a single Danish Cancer Centre

Background: The main indication for transoral robotic surgery (TORS) has been the primary treatment of oropharyngeal squamous cell carcinoma (OPSCC). In the western world this is highly relevant due to the increasing incidence of human papillomavirus (HPV)-positive OPSCC. In Denmark, TORS was implemented in 2013 for use in the protocolled primary treatment of OPSCC.Aims/objectives: To perform a year-by-year comparative analysis of indications for TORS, hospitalization and complication rates to identify optimal future indications for TORS.Methods and materials: This is a retrospective single-centre case review from 2013-2017. Data were collected from patient files through electronic health care systems.Results: Since 2013, there has been a change of indications from performing benign and salvage surgery to mainly primary treatment of OPSCC and diagnostic use in patients with cancer of unknown primary (CUP). The overall complication rates have reduced considerably over time.Conclusions and significance: Lower complication rates may be explained by improved surgical experience, through better patient selection and changes in indications for TORS. Future applications of TORS will be in the management of CUP and as part of a Danish national randomized clinical trial aiming to compare long-term functional outcomes after treatment of early-stage OPSCC with TORS versus radiation treatment.

Quality of Life After Primary TORS vs IMRT for Patients With Early-stage Oropharyngeal Squamous Cell Carcinoma

Quality of Life After Primary TORS vs IMRT for Patients With Early-stage Oropharyngeal Squamous Cell Carcinoma

Patients with early-stage oropharyngeal cancer can be identified with label-free serum proteomics

BackgroundThe increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) is mainly related to human papillomavirus (HPV) infection. As OPSCCs are often diagnosed at an advanced stage, mortality and morbidity remain high. There are no diagnostic biomarkers for early detection of OPSCC.MethodsSerum from 25 patients with stage I–II OPSCC, and 12 healthy controls, was studied with quantitative label-free proteomics using ultra-definition MSE. Statistical analyses were performed to identify the proteins most reliably distinguishing early-stage OPSCCs from controls. P16 was used as a surrogate marker for HPV. P16-positive and P16-negative tumours were analysed separately.ResultsWith two or more unique proteins per identification, 176 proteins were quantified. A clear separation between patients with early-stage tumours and controls was seen in principal component analysis. Latent structures discriminant analysis identified 96 proteins, most reliably differentiating OPSCC patients from controls, with 13 upregulated and 83 downregulated proteins in study cases. The set of proteins was studied further with network, pathway and protein–protein interaction analyses, and found to participate in lipid metabolism, for example.ConclusionsWe found a set of serum proteins distinguishing early-stage OPSCC from healthy individuals, and suggest a protein set for further evaluation as a diagnostic biomarker panel for OPSCC.

Time course of subacute pain after transoral robotic surgery (TORS) for oropharyngeal squamous cell carcinoma versus traditional bilateral tonsillectomy in adults – a case–control study

Objective: To examine pain after Transoral Robotic Surgery (TORS) for oropharyngeal squamous cell carcinoma (OPSCC) versus traditional bilateral tonsillectomy in adults.Methods: Pain evolvement was assessed in a prospective case–control design of 16 consecutive patients treated with TORS for early stage OPSCC versus 12 patients, who underwent bilateral tonsillectomy on suspicion of malignant disease. The TORS group received an optimized analgesia regime of preoperative oral celecoxib and gabapentin, intra- and postoperative high-dose intravenous dexamethasone, and regular postoperative oral contalgin, gabapentin, celecoxib, paracetamol and rescue morphine. The tonsillectomy group received the departmental standard analgesia regime with low-dose preoperative oral dexamethasone, celecoxib and paracetamol. Postoperative regular analgesia consisted of oral NSAID and paracetamol with weak opioids prescribed as required. Pain intensity was recorded at rest and during swallowing twice a day.Results: The median pain intensity on postoperative day (POD) 1–4 was 2 in the TORS group versus 4.5 in the tonsillectomy group. From POD 5-10 median pain intensity was 3.5 and 4, respectively. The median length of stay was 5 days in the TORS group and less than 24 hours in the tonsillectomy group.Conclusion: With an optimized analgesia regime TORS for OPSCC can be performed with postoperative pain levels comparable to bilateral tonsillectomy in adults.

Comparison of clinical, radiological and morphological features including the distribution of HPV E6/E7 oncogenes in resection specimens of oropharyngeal squamous cell carcinoma

BackgroundHuman papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) represents a distinct tumour entity in comparison to HPV-negative OPSCC. The clinical, radiological, morphological features and distribution of HPV E6/E7 mRNA were investigated in resected specimens of OPSCC. MethodsWe retrieved formalin-fixed, paraffin-embedded whole section slides from 24 p16/HPV-DNA positive and 18 p16/HPV-DNA negative primary tumours and 16 corresponding metastases in patients with early-stage OPSCC who underwent planned curative or diagnostic primary transoral robotic surgery. A detailed clinicoradiological and histopathological investigation of the tumours was performed along with detection of HPV E6/E7 mRNA by in situ hybridisation. ResultsHPV-driven OPSCC was characterised by non-keratinising morphology and was dominated by a cohesive invasion pattern at the leading edge of the tumour. Dysplastic zones of the squamous epithelium were strictly located in the tonsillar crypts in contrast to HPV-negative OPSCC which predominantly arised from the dysplastic surface epithelium. Thirteen HPV-driven OPSCC invaded through the tonsillar lymphoid compartment and into soft tissue, causing a stromal desmoplastic reaction. HPV mRNA was consistently but inhomogenously expressed in the entire tumour area and in the dysplastic squamous epithelium. There was no HPV expression in the adjacent normal epithelium and in the non-neoplastic tissues. ConclusionsThis study enhances the current understanding of HPV-driven OPSCC. Only tumours that invade through the lymphoid compartment induce a stromal desmoplastic reaction. A consistent but inhomogenous expression of E6 and E7 mRNA was found in tumour and dysplastic areas, emphasizing that the E6/E7 oncogenes are the driving factors in HPV-driven OPSCC.