Consensuses, controversies, and future directions in treatment deintensification for human papillomavirus-associated oropharyngeal cancer.

The most common cancer caused by human papillomavirus (HPV) infection in the United States is oropharyngeal cancer (OPC), and its incidence has been rising since the turn of the century. Because of substantial long-term morbidities with chemoradiation and the favorable prognosis of HPV-positive OPC, identifying the optimal deintensification strategy for this group has been a keystone of academic head-and-neck surgery, radiation oncology, and medical oncology for over the past decade. However, the first generation of randomized chemotherapy deintensification trials failed to change the standard of care, triggering concern over the feasibility of de-escalation. National database studies estimate that up to one third of patients receive nonstandard de-escalated treatments, which have subspecialty-specific nuances. A synthesis of the multidisciplinary deintensification data and current treatment standards is important for the oncology community to reinforce best practices and ensure optimal patient outcomes. In this review, the authors present a summary and comparison of prospective HPV-positive OPC de-escalation trials. Chemotherapy attenuation compromises outcomes without reducing toxicity. Limited data comparing transoral robotic surgery (TORS) with radiation raise concern over toxicity and outcomes with TORS. There are promising data to support de-escalating adjuvant therapy after TORS, but consensus on treatment indications is needed. Encouraging radiation deintensification strategies have been reported (upfront dose reduction and induction chemotherapy-based patient selection), but level I evidence is years away. Ultimately, stage and HPV status may be insufficient to guide de-escalation. The future of deintensification may lie in incorporating intratreatment response assessments to harness the powers of personalized medicine and integrate real-time surveillance.

Preoperative sleep-disordered breathing and craniofacial abnormalities are risk factors for postoperative sleep-disordered breathing in patients undergoing skin-flap oropharyngeal reconstruction surgery for oral cavity cancer: a prospective case-control study.

PURPOSE: After oropharyngeal reconstruction surgery, excessive flap volume within the oral cavity may increase the risk of pharyngeal obstruction during sleep. This prospective observational study aimed to test a hypothesis that the skin-flap oropharyngeal reconstructive surgery increases nocturnal apnea-hypopnea index (nAHI, primary variable) after surgery. METHODS: Adult patients undergoing oropharyngeal reconstruction surgery participated in this study. The hypothesis was tested by comparing the results of portable type 4 sleep study and craniofacial assessments with lateral head and neck computed tomography scout image before and after surgery. Multiple linear regression analyses were performed to identify predictors for nAHI increase after the surgery. RESULTS: In 15 patients, a postoperative sleep study was performed at 41 (27, 59) (median (IQR)) days after the surgery. nAHI did not increase after the surgery (mean (95% CI), 13.0 (7.2 to 18.7) to 18.4 (10.2 to 26.6) events.hour-1, p = 0.277), while apnea index significantly increased after the surgery (p = 0.026). Use of the pedicle flap for the oropharyngeal reconstruction (p = 0.051), small mandible (p = 0.008), longer lower face (0.005), and larger tongue size (p = 0.008) were independent predictors for worsening of nAHI after surgery. Hospital stay was significantly longer in patients with the pedicle flap (n = 8) than in those with the free flap (n = 7) (p = 0.014), and the period of hospital stay was directly associated with increase of nAHI after surgery (r = 0.788, p < 0.001, n = 15). CONCLUSIONS: Oropharyngeal reconstruction surgery worsens sleep-disordered breathing in some patients with craniofacial and surgical risk factors. TRIAL REGISTRATION: UMIN Clinical Trial Registry (UMIN000036260, March 22, 2019), https://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000036260.

Utility of video fluoroscopic swallow study in advancing oral diet post TORS for oropharyngeal malignancies.

OBJECTIVE: TORS is a minimally invasive surgical alternative to chemoradiotherapy for oropharyngeal malignancies. While early postoperative oropharyngeal dysphagia is linked to TORS, this study explores both subjective and objective swallowing outcomes. STUDY DESIGN: Retrospective and prospective review of the patients who underwent TORS for oropharyngeal malignancy from 2018 to 2023. SETTING: Single tertiary referral center. METHODS: Postoperative transnasal feeding tubes were administered to 142 patients undergoing TORS. Data on oncological, clinical, surgical, and pathological parameters, including VFSS records, pain with swallow, and feeding tube removal timing, were collected. Clinical swallow exam (CSE) was conducted on POD-1, with a formal swallow study pursued if inconclusive. Once a safe swallow was confirmed, oral diets were initiated, and the feeding tube removed, with most patients discharged on POD-2. RESULTS: At an average age of 59.3 years on the day of operation, the palatine tonsil (N = 101) was the predominant subsite. A dobhoff feeding tube was intraoperatively placed in 98 % of patients (N = 139). On POD-1, CSE was conducted in 119 patients, with 26 % (37/119) cleared for total oral diet (NOMS ≥ 4). Additionally, 30 out of 73 VFSS patients were cleared for total oral diet. A total of 54.9 % (78/142) had the feeding tube removed before discharge on POD-2, with a mean time of 6.5 ± 6.6 days. Overall, 71.1 % (101/142) achieved a total oral diet within one week after TORS. CONCLUSION: Early post-TORS swallowing is vital for oropharyngeal malignancies. VFSS assesses post-operative swallowing safety, allowing most patients to resume total oral nutrition shortly after TORS.

Patterns of recurrence in HNSCC patients treated definitively with upfront surgery, chemoradiation.

PURPOSE: Locally-advanced oropharynx (LA-OPSCC) and hypopharynx/larynx (LA-HPLSCC) cancers may be treated with surgical or non-surgical modalities. While survival outcomes are comparable, patterns of disease recurrence are not well established. METHODS: Retrospective review of 98 consecutive patients with LA-OPSCC or LA-HPLSCC treated by either surgery plus adjuvant therapy (S-POAT, n = 48) or chemoradiation (CRT, n = 50). RESULTS: CRT-treated patients had higher recurrence risk (42% vs 14.6%, p = 0.003). This was significant only among LA-OPSCC (p = 0.002) but not LA-HPLSCC patients (p = 0.159). Median time to recurrence in LA-OPSCC was 16.8 vs 11.6 months, and 16.6 vs 15.1 months in LA-HPLSCC, comparing surgically treated and CRT cohorts. Surgically-treated p16-negative LA-OPSCC experienced improved locoregional control than CRT-treated patients (100% vs 12.5%, p = 0.045) and 3-year RFS (83.0% vs 33.3%, p < 0.001). CONCLUSION: Locoregional control and RFS benefit was observed in surgically treated p16 negative LA-OPSCC patients. Locoregional recurrence is the main reason of treatment failure in LA-HNSCC, occurring commonly within the first 2 years post-treatment, regardless of treatment option.

Upfront surgery versus definitive radiotherapy: competing risk analyses for cancer-specific and noncancer mortality in oropharyngeal cancer.

PURPOSE: The optimal treatment strategy for oropharyngeal cancer (OPC) is undetermined. We aim to compare the survival outcomes of OPC patients treated with upfront surgery versus definitive radiotherapy (RT). METHODS: A total of 8057 cases were retrieved from the Surveillance, Epidemiology, and End Results database. Primary endpoints were cancer-specific and noncancer mortalities, which were estimated using cumulative incidence function and compared by Gray's test. Univariate and multivariate Fine-Gray subdistribution hazard models were used to estimate the effects of treatment modality on mortality. Subgroup analyses were performed in propensity-score-matched cohorts. All the analyses were conducted separately in human papillomavirus (HPV)-negative and HPV-positive cohorts. RESULTS: In the HPV-negative cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted subdistribution hazard ratio [SHR], 1.31; 95% confidence interval [CI], 1.05-1.64; P = 0.017) and noncancer mortality (adjusted SHR, 1.59; 95% CI 1.13-2.25; P = 0.008). In the HPV-positive cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted SHR, 1.51; 95% CI 1.23-1.85; P < 0.001) and noncancer mortality (adjusted SHR, 1.53; 95% CI 1.11-2.12; P = 0.009). CONCLUSION: Upfront surgery is a superior treatment modality compared with definitive RT in terms of lowering cancer-specific and noncancer mortality in OPC patients, regardless of HPV status. Further prospective clinical trials are needed to confirm our findings.

Salvage transoral robotic surgery in recurrent oropharyngeal carcinoma: a single-center retrospective study.

PURPOSE: Salvage surgery is still the best therapeutic option for resectable recurrent oropharyngeal squamous cell carcinoma (rOPSCC). Transoral robotic surgery may potentially reduce the morbidity of standard open approaches. The aim of the study is to present oncological and functional outcomes of a monocentric experience in salvage transoral robotic surgery. METHODS: We performed a single-center retrospective analysis of patients submitted to transoral robotic salvage surgery with or without neck dissection for cT1-3 rOPSCC. We investigated complication rate, survival outcomes (Overall Survival, Disease Specific Survival, Loco-Regional Recurrence Free Survival) and functional outcomes (tracheal tube and/or gastrostomy dependence). RESULTS: Sixty-one patients were included in the analysis. No major complications or perioperative deaths were recorded. The estimated 2-year OS was 76.7%, DSS 81.8% and LRRFS 50.5%. In multivariable analysis rpT, PNI (perineural infiltration) and HPV-positivity were significantly associated with LRRFS (Hazard Ratios: T3 vs T1 6.43, PNI yes vs no 4.19, HPV+ yes vs no 2.63). At last follow up, 97% of patients were tracheal tube-free, while 93% were gastrostomy-free. CONCLUSION: Transoral robotic salvage surgery is a successful treatment in selected patients affected by rOPSCC because it grants good oncologic and functional outcomes.

Indications for oropharyngeal biopsy in head and neck squamous cell carcinoma of unknown primary: A systematic review (HNSCCUP).

INTRODUCTION: Patients presenting with head and neck squamous cell carcinoma of unknown primary (HNSCCUP) remain challenging clinical scenarios as large variation exists in practices used to locate the primary. OBJECTIVE: The objective of this systematic review is to review of the literature and offer recommendations for oropharyngeal biopsies in HNSCCUP. METHOD: Pubmed, Medline and Embase were searched to identify studies from inception to October 2021. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. RESULTS: A total of 483 articles were included and screened, 41 studies met the inclusion criteria, including over 3400 patients from the original articles (122 of these patients were reported on in two sequential articles by a single author - table 1) and 4 large metaanalyses including 1852 patients. The primary site identification rate following random biopsies or deep tissue biopsies is less than 5% in most studies. The mean detection rate following ipsilateral tonsillectomy is 34%; two pooled analyses indicate that the mean detection rate following tongue base mucosectomy is 64%, with this figure rising when the tonsils are negative. CONCLUSIONS: High level evidence is lacking, with heterogeneity in the reported studies. Published meta-analyses are based on retrospective data. There is little evidence supporting the practice of random/non-directed oropharyngeal biopsies. Available evidence supports palatine tonsillectomy and tongue base mucosectomy compared to deep tissue biopsies.

A modified pull-through approach with a pedicled bone flap for oral and oropharyngeal cancer resection: a feasibility study.

PURPOSE: Compromised swallowing, speaking, and local complications are the major disadvantages of established approaches to the posterior tongue and oropharynx. The mandibular split involves an esthetically unpleasant bipartition of the lower lip and is prone to bony non-union or sequestration. The conventional pull-through technique on the other hand lacks the secure reattachment of the lingually released soft tissues. METHODS: The feasibility of a new modified pull-through approach was tested on three anatomical specimens. CAD/CAM cutting guides were used to design a retentive bone flap to properly refixate the genioglossus and geniohyoid muscles after the procedure. The radiographic assessment and treatment planning was performed on 12 cadavers. The entire procedure was tested surgically via dissection in three of those cases. This procedure was then applied in a clinical case. RESULTS: Precise repositioning and dynamic compression of bony segments was possible reproducibly and without injury to adjacent structures. In all dissected cases, a median lingual foramen was found and in two cases vessels entering it could be dissected Radiologic anatomical landmarks were sufficient in all 12 cases to perform the clinical planning procedure. Clinically, the osteotomized segment demonstrated good blood supply and plateless repositioning was verified postoperatively via cone beam scan. CONCLUSION: The method presented is safe and easy to perform. Individual cutting guides improve the safety and accuracy of the procedure, potentially eliminating the need for osteosynthesis. We provide the anatomical and radiologic basis for clinical evaluation of this pedicled bone flap procedure and present the clinical application of this modified pull-through approach.

[Surgical Treatment of Oropharyngeal Cancer - Recommendations of the Current German S3 Guideline, Part I]. / Chirurgische Therapie des Oropharynxkarzinoms: Empfehlungen der aktuellen S3-Leitlinie ­ Teil I.

In general, a trend towards transoral resection (as opposed to classic open approaches) + neck dissection + adjuvant radio- (chemo-) therapy has been observed for oropharyngeal carcinoma over the last 20 years. Techniques of transoral surgery (TOS), including transoral laser microsurgery (TLM) and transoral robotic surgery (TORS) have been propagated in retrospective comparisons with conventional surgery or primary radiochemotherapy as gentle, minimally invasive procedures with good late functional results. Meta-analyses of mostly uncontrolled retrospective analyses suggest that TORS may have better disease-free survival (DFS) and a reduced risk of free flap reconstruction compared with open surgery. TORS (TOS) was associated with fewer tumor-positive resection margins (R1), a lower number of recurrences, fewer intraoperative tracheostomies, a shorter inpatient stay and a shorter duration of postoperative nasal tube feeding compared to open surgery. In principle, based on the best evidence currently available from registry studies, stage I-II oropharyngeal carcinomas can be treated either with primary surgery or radiochemotherapy with a comparable chance of survival. With comparable evidence for stage III and IVa, p16neg. oropharyngeal carcinomas, the majority of authors advocate primary surgery followed by adjuvant radiotherapy or radiochemotherapy as the treatment of first choice. For p16pos. patients the results of registry studies are inconsistent, although the largest registry study on 450 HPV-positive stage III patients shows a significant superiority of primary surgery + adjuvant radiochemotherapy. Since all registry studies did not adjust for smoking status, among other factors, the current data situation should be evaluated with the necessary caution.

[Surgical Treatment of Hypopharyngeal Carcinoma, Neck Dissection and Adjuvant Postoperative Therapy of Oropharyngeal and Hypopharyngeal Cancer: Recommendations of the current S3 Guideline - Part II]. / Neck Dissection und adjuvante postoperative Therapie beim Oro- und Hypopharynxkarzinom: Empfehlungen der aktuellen S3-Leitlinie ­ Teil II.

Part II of the S3 guideline report deals with the surgical treatment of hypopharyngeal carcinoma, neck dissection for oropharyngeal and hypopharyngeal carcinomas and adjuvant therapy options. Primary surgical therapy ± adjuvant radio- or radiochemotherapy and primary radio- or radiochemotherapy are established as primary therapies for local-regional hypopharyngeal carcinomas. Direct randomized comparisons of both basic therapeutic procedures were never conducted. Available registry data show a worse prognosis of hypopharyngeal carcinoma compared to oropharyngeal carcinomas in all locoregional tumor stages, regardless of the treatment method. For T1N0-T2N0 squamous cell carcinoma of the hypopharynx, there are no relevant differences in overall survival and locoregional relapse rate between primary surgical and primary non-surgical treatment. Primary surgical therapy ± adjuvant radiotherapy or radiochemotherapy and primary radiotherapy or radiochemotherapy are established as primary therapies for advanced but locoregionally limited hypopharyngeal carcinomas. Neck dissection is an integral part of the primary surgical treatment of oropharyngeal and hypopharyngeal cancer. There are only a few randomized studies on non-surgical organ preservation for advanced hypopharyngeal cancer as an alternative to pharyngolaryngectomy, but these have led to the recommendation of alternative concepts in the new guideline. The indication and implementation of postoperative adjuvant radiotherapy and radiochemotherapy for hypopharyngeal carcinoma do not differ from those for HPV/p16-negative and -positive oropharyngeal carcinoma.

[Therapeutic efficacy of transoral robotic surgery with the da Vinci robot system for the treatment of oropharyngeal squamous cell carcinoma].

Objective: To evaluate the clinical efficacy of transoral robotic surgery (TORS) with the da Vinci robot system in the treatment of oropharyngeal squamous cell carcinoma (OPSCC). Methods: A mixed cohort study was conducted to collect and analyze the clinical data of OPSCC patients who underwent TORS at the Eye & ENT Hospital, Fudan University between July 2020 and February 2023 (TORS group). OPSCC patients who underwent conventional surgery between January 2016 and September 2020 were included as the control group. The baseline information, incidence of complications and follow-up data were compared between the two groups. Results: A total of 166 patients were included, with 102 cases (81 males and 21 females) in the TORS group [mean age: (59.1±9.8) years] and 64 cases (54 males and 10 females) in the control group [ mean age: (57.6±9.7) years]. Compared with the control group, the TORS group had lower postoperative bleeding rate [2.9% (3/102) vs 10.9% (7/64), P=0.035] and infection rate [1.0% (1/102) vs 18.8% (12/64), P<0.001]. No statistically significant differences were observed in tracheotomy rate [46.1% (47/102) vs 59.4% (38/64), P=0.070] and median length of hospital stay [8 (7, 10) d vs 10 (4, 12) d, P=0.088]. After propensity score matching, compared with the control group, the TORS group had lower postoperative infection rate [0 (0/31) vs 19.4% (6/31), P=0.032] and median length of hospital stay [7 (7, 10) d vs 10 (8, 12) d, P=0.031]. No statistically significant differences were found in postoperative bleeding rate [3.2% (1/31) vs 6.5% (2/31), P=1.000] and tracheotomy rate [22.6% (7/31) vs 45.2% (14/31), P=0.060] between the two groups. Moreover, 1-and 2-year disease-free survival rates were 96.3% and 94.6% in the TORS group, and 90.6% and 84.3% in the control group, respectively (P=0.233). The 1-and 2-year cancer-specific survival rates were both 100% in the TORS group, and 96.9% and 93.8% in the control group, respectively (P=0.539). Conclusion: TORS for OPSCC is associated with high clinical safety and favorable oncological outcomes.

Compartmental Transoral Robotic Lateral Oropharyngectomy with the da Vinci Single-Port System: Surgical Technique.

BACKGROUND: Transoral robotic surgery (TORS) has renovated the surgical management of oropharyngeal squamous cell carcinoma (OPSCC), allowing a minimally invasive surgical approach with optimal oncological outcomes. The recent introduction of the da Vinci Single Port (SP) system resulted in a considerable improvement of TORS technique. METHODS: In this video, we illustrate the transoral robotic lateral oropharyngectomy performed with the da Vinci SP system in a 50-year-old male patient suffering from a p16+ oropharyngeal squamous cell carcinoma cT4N1M0. RESULTS: The transoral robotic lateral oropharyngectomy is illustrated step by step. The structures encountered during the resection are described, and the surgical margins are defined based on anatomical landmarks. The most critical regions encountered during resection are pointed out, and the tip and tricks of this surgery are reported. CONCLUSIONS: A step-by-step transoral lateral oropharyngectomy is described to increase its reproducibility. The da Vinci SP system owns various benefits for performing transoral lateral oropharyngectomy due to the increased maneuverability in the narrower oral cavity working spaces.

Management of Recurrent HPV-Positive Oropharyngeal Squamous Cell Carcinoma: a Contemporary Review.

PURPOSE OF REVIEW: To review the impact of contemporary treatment strategies on salvage outcomes in patients with recurrent human papilloma virus-positive oropharyngeal squamous cell carcinoma (HPV + OPSCC). RECENT FINDINGS: Secondary to HPV, changes in disease biology have impacted primary treatments and subsequent approaches to patients with recurrence. With treatment strategies more inclusive of upfront surgery, the characteristics of patients with recurrence HPV + OPSCC have been further redefined. Less invasive endoscopic surgical approaches such as transoral robotic surgery (TORS), and the continued refinement of conformal radiotherapy techniques, have improved treatment options for patients with recurrent HPV + OPSCC. Systemic treatment options have continued to expand including potentially effective immune-based therapies. Effective surveillance with systemic and oral biomarkers offers hope of earlier detection of recurrence. Management of patients with recurrent OPSCC remains difficult. Modest improvements in salvage treatment have been observed within the HPV + OPSCC cohort largely reflecting disease biology and improved treatment techniques.

Interventions for the treatment of oral cavity and oropharyngeal cancers: surgical treatment.

BACKGROUND: Surgery is a common treatment option in oral cavity cancer (and less frequently in oropharyngeal cancer) to remove the primary tumour and sometimes neck lymph nodes. People with early-stage disease may undergo surgery alone or surgery plus radiotherapy, chemotherapy, immunotherapy/biotherapy, or a combination of these. Timing and extent of surgery varies. This is the third update of a review originally published in 2007. OBJECTIVES: To evaluate the relative benefits and harms of different surgical treatment modalities for oral cavity and oropharyngeal cancers. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 9 February 2022. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared two or more surgical treatment modalities, or surgery versus other treatment modalities, for primary tumours of the oral cavity or oropharynx. DATA COLLECTION AND ANALYSIS: Our primary outcomes were overall survival, disease-free survival, locoregional recurrence, and recurrence; and our secondary outcomes were adverse effects of treatment, quality of life, direct and indirect costs to patients and health services, and participant satisfaction. We used standard Cochrane methods. We reported survival data as hazard ratios (HRs). For overall survival, we reported the HR of mortality, and for disease-free survival, we reported the combined HR of new disease, progression, and mortality; therefore, HRs below 1 indicated improvement in these outcomes. We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: We identified four new trials, bringing the total number of included trials to 15 (2820 participants randomised, 2583 participants analysed). For objective outcomes, we assessed four trials at high risk of bias, three at low risk, and eight at unclear risk. The trials evaluated nine comparisons; none compared different surgical approaches for excision of the primary tumour. Five trials evaluated elective neck dissection (ND) versus therapeutic (delayed) ND in people with oral cavity cancer and clinically negative neck nodes. Elective ND compared with therapeutic ND probably improves overall survival (HR 0.64, 95% confidence interval (CI) 0.50 to 0.83; I2 = 0%; 4 trials, 883 participants; moderate certainty) and disease-free survival (HR 0.56, 95% CI 0.45 to 0.70; I2 = 12%; 5 trials, 954 participants; moderate certainty), and probably reduces locoregional recurrence (HR 0.58, 95% CI 0.43 to 0.78; I2 = 0%; 4 trials, 458 participants; moderate certainty) and recurrence (RR 0.58, 95% CI 0.48 to 0.70; I2 = 0%; 3 trials, 633 participants; moderate certainty). Elective ND is probably associated with more adverse events (risk ratio (RR) 1.31, 95% CI 1.11 to 1.54; I2 = 0%; 2 trials, 746 participants; moderate certainty). Two trials evaluated elective radical ND versus elective selective ND in people with oral cavity cancer, but we were unable to pool the data as the trials used different surgical procedures. Neither study found evidence of a difference in overall survival (pooled measure not estimable; very low certainty). We are unsure if there is a difference in effect on disease-free survival (HR 0.57, 95% CI 0.29 to 1.11; 1 trial, 104 participants; very low certainty) or recurrence (RR 1.21, 95% CI 0.63 to 2.33; 1 trial, 143 participants; very low certainty). There may be no difference between the interventions in terms of adverse events (1 trial, 148 participants; low certainty). Two trials evaluated superselective ND versus selective ND, but we were unable to use the data. One trial evaluated supraomohyoid ND versus modified radical ND in 332 participants. We were unable to use any of the primary outcome data. The evidence on adverse events was very uncertain, with more complications, pain, and poorer shoulder function in the modified radical ND group. One trial evaluated sentinel node biopsy versus elective ND in 279 participants. There may be little or no difference between the interventions in overall survival (HR 1.00, 95% CI 0.90 to 1.11; low certainty), disease-free survival (HR 0.98, 95% CI 0.90 to 1.07; low certainty), or locoregional recurrence (HR 1.04, 95% CI 0.91 to 1.19; low certainty). The trial provided no usable data for recurrence, and reported no adverse events (very low certainty). One trial evaluated positron emission tomography-computed tomography (PET-CT) following chemoradiotherapy (with ND only if no or incomplete response) versus planned ND (before or after chemoradiotherapy) in 564 participants. There is probably no difference between the interventions in overall survival (HR 0.92, 95% CI 0.65 to 1.31; moderate certainty) or locoregional recurrence (HR 1.00, 95% CI 0.94 to 1.06; moderate certainty). One trial evaluated surgery plus radiotherapy versus radiotherapy alone and provided very low-certainty evidence of better overall survival in the surgery plus radiotherapy group (HR 0.24, 95% CI 0.10 to 0.59; 35 participants). The data were unreliable because the trial stopped early and had multiple protocol violations. In terms of adverse events, subcutaneous fibrosis was more frequent in the surgery plus radiotherapy group, but there were no differences in other adverse events (very low certainty). One trial evaluated surgery versus radiotherapy alone for oropharyngeal cancer in 68 participants. There may be little or no difference between the interventions for overall survival (HR 0.83, 95% CI 0.09 to 7.46; low certainty) or disease-free survival (HR 1.07, 95% CI 0.27 to 4.22; low certainty). For adverse events, there were too many outcomes to draw reliable conclusions. One trial evaluated surgery plus adjuvant radiotherapy versus chemotherapy. We were unable to use the data for any of the outcomes reported (very low certainty). AUTHORS' CONCLUSIONS: We found moderate-certainty evidence based on five trials that elective neck dissection of clinically negative neck nodes at the time of removal of the primary oral cavity tumour is superior to therapeutic neck dissection, with increased survival and disease-free survival, and reduced locoregional recurrence. There was moderate-certainty evidence from one trial of no difference between positron emission tomography (PET-CT) following chemoradiotherapy versus planned neck dissection in terms of overall survival or locoregional recurrence. The evidence for each of the other seven comparisons came from only one or two studies and was assessed as low or very low-certainty.

Does Bulky Adenopathy in Human Papilloma Virus-Positive Oropharyngeal Squamous Cell Carcinoma Require a Planned Post-Treatment Neck Dissection for Occult Residual Disease?

PURPOSE: A planned neck dissection was traditionally considered for a large nodal disease after definitive chemoradiation, yet controversy exists for the human papilloma virus-positive oropharyngeal squamous cell carcinoma (HPV OPSCC). We aimed to measure the frequency of persistent occult neck disease in planned neck dissection for HPV OPSCC presenting with a large (≥3.0 cm) nodal burden. METHODS: We designed a retrospective cohort study at a single tertiary referral institution. The study population was sampled from 2006 to 2018 and subjects with HPV OPSCC and adenopathy ≥3.0 cm. Inclusion criteria encompassed subjects who completed primary chemoradiation therapy (CRT) or primary radiation therapy (RT), and subsequently underwent a planned neck dissection. We excluded subjects who did not complete therapy or had less than 1-year follow-up. Our primary predictor variable was the size of cervical adenopathy on presentation (3.0-3.9 cm, 4.0-4.9 cm, 5.0-5.9 cm, and ≥6.0 cm). Our primary outcome of interest was the presence of disease based on the histopathology review. Other variables included the demographics, primary treatment with CRT or RT, and post-treatment clinical or radiographic evidence of disease. Chi-square testing was used to compare rates of persistent disease, with varying sizes of cervical adenopathy on presentation. The alpha level for statistical significance was set at 0.05. RESULTS: A total of 86 subjects were analyzed, with forty-one females and forty-five males, ranging from 36 to 77 years (mean 54.6 years). From the total study sample, 35% showed persistent disease, and 67% of those subjects had occult disease at the time of planned neck dissection. Greater than 20% of subjects had persistent disease when the nodal burden was ≥3.0 cm at presentation. Furthermore, there was a statistically significant difference in the rates of persistent microscopic disease among subjects with nodal burden of different sizes based on chi-square testing (P = .01, χ2 = 10.66). CONCLUSIONS: Our data suggest that subjects with HPV OPSCC presenting with a nodal burden ≥3.0 cm are likely to have 23% chance of persistent occult neck disease after primary CRT or RT. These findings may support the routine treatment of these subjects with a planned neck dissection after initial therapy to confirm or surgically complete disease eradication.

Protection of the marginal mandibular branches of the facial nerves by different surgical procedures in comprehensive cervical lymphadenectomy for locally advanced oral and oropharyngeal cancer: a multicenter experience.

OBJECTIVE: According to the different characteristics of patients and cervical lymph node metastasis of oral and oropharyngeal cancer, the marginal mandibular branches of facial nerves were treated by different surgical procedures, and the safety and protective effects of different surgical procedures were investigated. METHODS: One hundred ninety-seven patients with oral and oropharyngeal cancer satisfying the inclusion criteria were selected. According to the different characteristics of patients and cervical metastatic lymph nodes, three different surgical procedures were used to treat the marginal mandibular branches of the facial nerve: finding and exposing the marginal mandibular branches of the facial nerves at the mandibular angles of the platysma flaps, finding and exposing the marginal mandibular branches of facial nerves at the intersections of the distal ends of facial arteries and veins with the mandible, and not exposing the marginal mandibular branches of the facial nerves. The anatomical position, injury, and complications of the marginal mandibular branches of the facial nerves were observed. RESULTS: The marginal mandibular branches of the facial nerves were found and exposed at the mandibular angles of the platysma flaps in 102 patients; the marginal mandibular branches of facial nerves were found and exposed at the intersections of the distal ends of the facial arteries and veins with the mandibles in 64 patients; the marginal mandibular branches of facial nerves were not exposed in 31 patients; among them, four patients had permanent injury of the marginal mandibular branches of the facial nerves, and temporary injury occurred in seven patients. There were statistically significant differences in the protection of the mandibular marginal branch of the facial nerve among the three different surgical methods (P = 0.0184). The best protective effect was to find and expose the mandibular marginal branch of the facial nerve at the mandibular angle of the platysma muscle flap, and the injury rate was only 2.94%. CONCLUSION: The three different surgical procedures were all safe and effective in treating the marginal mandibular branches of the facial nerves, the best protective effect was to find and expose the mandibular marginal branch of the facial nerve at the mandibular angle of the platysma muscle flap.

Facility volume and survival: Human papilloma virus positive oropharyngeal squamous cell carcinoma.

BACKGROUND: To analyze the impact of facility volume on survival for human papilloma virus positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC) patients. METHODS: Patients treated for HPV+ OPSCC from 2010 to 2017 were queried from the National Cancer Database. Facilities of average annual case volume <50th percentile were categorized as low-volume (LV) and >95th percentile as high-volume (HV). RESULTS: 11,546 were included, with 10,305 patients (89.3 %) treated at LV and 1241 (10.7 %) at HV facilities. A greater proportion of cases involving resection of base of tongue and lingual tonsil were treated at HV (30.3 %) compared to LV (22.3 %) facilities (p < 0.001). Patients treated at a HV facility had greater percentage of clinical T4 (11.2 % vs. 8.6 %, p = 0.001) and N+ disease (90.5 % vs. 85.7 %, p < 0.001) patients. Survival analysis showed no statistically significant difference between five-year overall survival rates by facility volume (p = 0.388) for all patients. On multivariable analysis, facility volume was not associated with survival (HR: 0.968 [0.758-1.235], p = 0.791). These trends were found for both patients undergoing primary surgery or chemoradiotherapy. CONCLUSION: Our data indicates that patients with HPV+ OPSCC do not experience a survival benefit with treatment at HV facility, suggesting these patients may be adequately treated at LV centers.

Outcomes following oropharyngeal squamous cell carcinoma resection and bilateral neck dissection with or without contralateral postoperative radiotherapy of the pathologically node-negative neck.

PURPOSE: There are no consensus guidelines regarding the postoperative treatment of the contralateral pathologically node-negative neck in oropharyngeal squamous cell carcinoma. This study aimed to determine if omission of postoperative irradiation of the contralateral pathologically node-negative neck affects oncological outcomes. METHODS: We retrospectively identified 84 patients with primary surgical treatment including bilateral neck dissection and postoperative (chemo-)radiotherapy (PO(C)RT). Survival was analyzed using the log-rank test and the Kaplan-Meier method. RESULTS: Patients showed no decrease in tumor-free, cause-specific (CSS), or overall survival (OS) when PO(C)RT of the contralateral pathologically node-negative neck was omitted. Increased OS was found in patients with unilateral PO(C)RT and especially an increased OS and CSS was found in unilateral PO(C)RT and in tumors arising from lymphoepithelial tissue. CONCLUSIONS: Omitting the contralateral pathologically node-negative neck appears to be safe in terms of survival and our retrospective study advocates further prospective randomized control de-escalation trials.

Lymph node metastasis in level IIb in oropharyngeal squamous cell carcinoma: a multicentric, longitudinal, retrospective analysis.

INTRODUCTION: Nowadays, 70% of patients in Europe and the USA are affected by a p16 + , potentially HPV driven oropharyngeal squamous cell carcinoma. However, despite the improved survival rate in this group, the quality-of-life remains low in cases which neck dissection took place. In this vein, in recent years, some surgeons have considered to avoid dissection of level IIB, proposing a supra-selective non-IIb neck dissection. MATERIALS AND METHODS: A retrospective, longitudinal, multicentric study was conducted, including patients with pathologically confirmed primary HPV + or HPV - OPSCC who went through surgical treatment for the primary lesion and neck dissection. RESULTS: 141 patients were included. Among them, 99 (70.2%) were male and 42 (29.8%) were female. The mean age was 62 ± 9 years (range 36-81). The most frequent anatomical location was the tonsil in 63 (44.7%) of patients. The most common approach was the classic transoral oropharyngectomy in 51 (36.2%) patients. Immunohistochemistry for p16 was positive in 62 (44%) patients. One-hundred and five (74.5%) patients received a unilateral ND, and a 36 (25.5%) a bilateral ND. Of those, a 12.8% (18/141) of patients were level IIb LN + . According to our results, level IIb ND should be considered in patients underwent therapeutic ND with positive LN metastasis in level IIa (OR = 9.83; 95% CI 3.463-27.917) or III (OR = 6.25; 95% CI 2.158-18.143), advanced (T3/T4) oropharyngeal primary tumors (OR = 3.38; 95% CI 1.366-8.405), and patients with ENE (OR = 6.56; 95% CI 2.182-19.770), regardless of p16 status. CONCLUSIONS: According to our results, level IIb ND should be considered in patients who underwent therapeutic ND with positive LN metastasis in level IIa or III, advanced oropharyngeal primary tumors, and patients with ENE, independently of p16 status. Prospective data are necessary to definitively ensure the safety of omitting ipsilateral or contralateral level IIb ND in cN - patients with early stage disease.

Staged neck dissection prior to transoral robotic surgery for oropharyngeal cancer: does it reduce post-operative complication rates? A multi-centre study of 104 patients.

PURPOSE: Transoral robotic surgery (TORS) has become increasingly recognised as a safe and effective treatment for early oropharyngeal squamous cell carcinoma, often performed in conjunction with neck dissection (ND) and vessel ligation. It has been proposed that performing the neck dissection in a staged fashion prior to TORS results in low rates of transoral haemorrhage and pharyngocutaneous fistula, and may aid in TORS patient selection by eliminating patients who would require multi-modality treatment based on nodal pathology. This study aims to assess the effect of staged neck dissection with TORS in mitigating pharyngocutaneous fistulae and post-operative haemorrhage as well as the impact of staged ND on TORS patient selection. METHODS: A retrospective cohort analysis was performed of patients undergoing staged ND with intent to proceed to TORS at two Australian hospitals between 2014 and 2022. Incidence of post-operative haemorrhage and pharyngocutaneous fistula and length of inpatient stay was identified. The number of patients who did not proceed to TORS was recorded. RESULTS: One hundred and four patients were identified who underwent staged neck dissection with an intention to proceed to TORS. Six patients did not proceed to TORS following pathological assessment of the neck dissection specimen and ninety-eight patients (91 primary, 7 salvage) underwent TORS. There were six cases of secondary haemorrhage (one major, two intermediate and three minor). There were no cases of pharyngocutaneous fistula. CONCLUSION: Staged neck dissection prior to TORS results in low rates of haemorrhage and pharyngocutaneous fistula and can improve TORS patient selection.