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.

INTRODUCTION: The 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. METHODS: All 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. RESULTS: The 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. CONCLUSION: Excellent 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.

Mesenchymal Stem/Stromal Cell Therapy for Radiation-Induced Xerostomia in Previous Head and Neck Cancer Patients: A Phase 2 Randomised, Placebo-Controlled Trial.

PURPOSE: No effective treatment exists for radiation-induced xerostomia. The objective of this study was to compare the effect of adipose-derived mesenchymal stem/stromal cell (ASC) injection, relative to placebo, on salivary gland function in patients with radiation-induced xerostomia. PATIENT AND METHODS: In this single-centre, double-blind, placebo-controlled trial, patients with hyposalivation were randomised to receive ultrasound-guided injections of allogeneic ASCs or placebo into the submandibular glands. Patients were followed for four months. We evaluated unstimulated whole salivary flow rate (UWS), stimulated salivary flow rate, and patient-reported outcomes. Adverse events were recorded and immune response determined in blood samples. RESULTS: We enrolled 120 patients. ASC treatment resulted in a statistically significant UWS increase of 0.04 [95% CI 0.02 to 0.06] mL/min (38%) compared to pre-treatment baseline whereas placebo treatment did not cause a significant increase (0.01 [-0.01 to 0.04] mL/min (21%)). Both the ASC and placebo treatment yielded notable symptom reductions, with dry mouth decreasing by 13.6 units and 7.7 units, sticky saliva decreased by 14.8 units and 9.3 units, swallowing difficulties decreased by 7.9 and 8.0 units, and the summary score of the Xerostomia Questionnaire decreased 5.9 units and 5.1 units for the ASC and placebo-arm, respectively. We found no statistically significant group difference between the ASC and placebo-arm for any of the outcomes. CONCLUSION: We could not confirm superiority of the ASC relative to placebo. ASC therapy significantly improved UWS in previous head and neck cancer patients, whereas placebo resulted in an insignificant increase.

Clinical and prognostic differences in oropharyngeal squamous cell carcinoma in USA and Denmark, two HPV high-prevalence areas.

BACKGROUND: Uncertainty persists regarding clinical and treatment variations crucial to consider when comparing high human papillomavirus (HPV)-prevalence oropharyngeal squamous cell carcinoma (OPSCC) cohorts for accurate patient stratification and replicability of clinical trials across different geographical areas. METHODS: OPSCC patients were included from The University of Texas MD Anderson Cancer Center (UTMDACC), USA and from The University Hospital of Copenhagen, Denmark from 2015-2020, (n = 2484). Outcomes were 3-year overall survival (OS) and recurrence-free interval (RFI). Subgroup analyses were made for low-risk OPSCC patients (T1-2N0M0) and high-risk patients (UICC8 III-IV). RESULTS: There were significantly more HPV-positive (88.2 % vs. 63.1 %), males (89.4 % vs. 74.1 %), never-smokers (52.1 % vs. 23.7 %), lower UICC8-stage (I/II: 79.3 % vs. 68 %), and fewer patients treated with radiotherapy (RT) alone (14.8 % vs. 30.3 %) in the UTMDACC cohort. No difference in the adjusted OS was observed (hazard ratio [HR] 1.21, p = 0.23), but a significantly increased RFI HR was observed for the Copenhagen cohort (HR: 1.74, p = 0.003). Subgroup analyses of low- and high-risk patients revealed significant clinical and treatment differences. No difference in prognosis was observed for low-risk patients, but the prognosis for high-risk patients in the Copenhagen cohort was worse (OS HR 2.20, p = 0.004, RFI HR 2.80, p = 0.002). CONCLUSIONS: We identified significant differences in clinical characteristics, treatment modalities, and prognosis between a Northern European and Northern American OPSCC population. These differences are important to consider when comparing outcomes and for patient stratification in clinical trials, as reproducibility might be challenging.

Validation of the VisionArray® Chip Assay for HPV DNA Testing in Histology Specimens of Oropharyngeal Squamous Cell Carcinoma.

BACKGROUND: The detection of human papillomavirus (HPV) has several implications in the diagnostic work-up and management of oropharyngeal squamous cell carcinoma (OPSCC). The choice of HPV detection assay and testing algorithms differ across institutions and vary in cost, detection targets, technical feasibility, and turnaround time. In this study, we aimed to validate the VisionArray® HPV Chip for formalin-fixed and paraffin-embedded (FFPE) samples of OPSCC using the previously applied standard pan-HPV DNA PCR assay as a reference. METHODS: The validation cohort consisted of FFPE tissue samples from patients previously diagnosed with HPV DNA-positive OPSCC (n = 80), HPV DNA-negative OPSCC (n = 21), and a benign group of tumor samples consisting of Warthin's tumors (n = 20) and branchial cleft cysts of the lateral neck (n = 14). All samples were tested with p16 immunohistochemistry, pan-HPV DNA PCR, and the VisionArray® HPV Chip. RESULTS: The overall sensitivity and specificity of the VisionArray® HPV Chip assay were 100% [95% CI 95.5%; 100.0%] and 96.3% [95% CI 87.3%; 99.6%] and the positive predictive value and negative predictive value were 97.6% [95% CI 91.5%; 99.7%] and 100% [95% CI 93.2%; 100%], respectively. CONCLUSIONS: The VisionArray® HPV Chip assay can be recommended for high-risk HPV testing in FFPE tissue samples from OPSCC, providing both a fast and simultaneous genotyping for 41 clinically relevant HPV types.

The Genetic Profile of Large B-Cell Lymphomas Presenting in the Ocular Adnexa.

To provide insights into targetable oncogenic pathways, this retrospective cohort study investigated the genetic profile of 26 patients with diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), and two patients with high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL) presenting in the ocular adnexa. Pathogenic variants and copy number variations in 128 B-cell lymphoma-relevant genes were analyzed by targeted next-generation sequencing. Genetic subtypes were determined with the LymphGen algorithm. Primary ocular adnexal DLBCL-NOS constituted 50% (n = 14) and was generally characterized by non-germinal center B-cell origin (non-GCB) (n = 8, 57%), and LymphGen MCD subtype (n = 5, 36%). Primary ocular adnexal DLBCL-NOS presented pathogenic variants in genes involved in NF-κB activation and genes which are recurrently mutated in other extranodal lymphomas of non-GCB origin, including MYD88 (n = 4, 29%), CD79B (n = 3, 21%), PIM1 (n = 3, 21%), and TBL1XR1 (n = 3, 21%). Relapsed DLBCL-NOS presenting in the ocular adnexa (n = 6) were all of non-GCB origin and frequently of MCD subtype (n = 3, 50%), presenting with a similar genetic profile as primary ocular adnexal DLBCL-NOS. These results provide valuable insights into genetic drivers in ocular adnexal DLBCL-NOS, offering potential applications in future precision medicine.

Advances in testing for human papillomavirus -mediated head and neck cancer.

PURPOSE OF REVIEW: New evidence has recently emerged regarding the utility and benefits of dual p16 INKa (p16) and Human papillomavirus (HPV) status testing when determining the diagnosis and prognosis of patients with oropharyngeal cancer. RECENT FINDINGS: HPV RNA polymerase chain reaction (PCR) is the most accurate diagnostic test. The other assays (HPV DNA PCR, HPV DNA/RNA in-situ hybridization (ISH) and p16) applied to formalin fixed tumour tissue have varying but high sensitivities and specificities. Dual p16 and HPV testing identifies discordant (p16+/HPV- or p16-/HPV+) results in 9.2% of cases, who have significantly poorer prognoses than p16+/HPV+, particularly in smokers. The proportion of discordant cases varies by region, and appears to be highest in regions with lowest attributable (p16+/HPV+) fractions. Dual testing improves prognostication for oropharyngeal cancer cases by identifying discordant cases and improving the prognostic power of the Tumour Node Metastasis (TNM) classification, especially in regions with high discordant rates. SUMMARY: Dual testing is essential when considering patients for clinical trials of treatment de-escalation, and may be important when counselling patients on prognosis, especially in regions with high discordant rates and in smokers.

Meta-analysis of ACE inhibitor-induced angioedema identifies novel risk locus.

BACKGROUND: Angioedema is a rare but potentially life-threatening adverse drug reaction in patients receiving angiotensin-converting enzyme inhibitors (ACEis). Research suggests that susceptibility to ACEi-induced angioedema (ACEi-AE) involves both genetic and nongenetic risk factors. Genome- and exome-wide studies of ACEi-AE have identified the first genetic risk loci. However, understanding of the underlying pathophysiology remains limited. OBJECTIVE: We sought to identify further genetic factors of ACEi-AE to eventually gain a deeper understanding of its pathophysiology. METHODS: By combining data from 8 cohorts, a genome-wide association study meta-analysis was performed in more than 1000 European patients with ACEi-AE. Secondary bioinformatic analyses were conducted to fine-map associated loci, identify relevant genes and pathways, and assess the genetic overlap between ACEi-AE and other traits. Finally, an exploratory cross-ancestry analysis was performed to assess shared genetic factors in European and African-American patients with ACEi-AE. RESULTS: Three genome-wide significant risk loci were identified. One of these, located on chromosome 20q11.22, has not been implicated previously in ACEi-AE. Integrative secondary analyses highlighted previously reported genes (BDKRB2 [bradykinin receptor B2] and F5 [coagulation factor 5]) as well as biologically plausible novel candidate genes (PROCR [protein C receptor] and EDEM2 [endoplasmic reticulum degradation enhancing alpha-mannosidase like protein 2]). Lead variants at the risk loci were found with similar effect sizes and directions in an African-American cohort. CONCLUSIONS: The present results contributed to a deeper understanding of the pathophysiology of ACEi-AE by (1) providing further evidence for the involvement of bradykinin signaling and coagulation pathways and (2) suggesting, for the first time, the involvement of the fibrinolysis pathway in this adverse drug reaction. An exploratory cross-ancestry comparison implicated the relevance of the associated risk loci across diverse ancestries.

Sinonasal DLBCL: molecular profiling identifies subtypes with distinctive prognosis and targetable genetic features.

ABSTRACT: Primary sinonasal diffuse large B-cell lymphoma (PSDLBCL) is a rare lymphoma with a variable prognosis and a unique relapse/dissemination pattern involving the central nervous system and skin. The underlying molecular mechanisms leading to this heterogeneity and progression pattern remain uncharted, hampering patient-tailored treatment. To investigate associated mechanisms, we analyzed clinical data and used immunohistochemistry, gene-expression profiling, cytogenetics, and next-generation sequencing in a cohort of 117 patients with PSDLBCL. The distribution in cell-of-origin (COO) was 68 (58%) activated B-cell (ABC), 44 (38%) germinal center B-cell (GCB), and 5 (4%) unclassifiable. COO was significantly associated with progression-free survival (PFS) and lymphoma-specific mortality (LSM) in both the overall cohort (5-year PFS: ABC, 43% vs GCB, 73%; LSM: ABC, 45% vs GCB, 14%) and in the subgroup of patients receiving immunochemotherapy (5-year PFS: ABC, 55% vs GCB, 85%; LSM: ABC, 28% vs GCB, 0%). ABC lymphomas were mainly MCD class, showing a high prevalence of MYD88 (74%) and CD79B (35%) mutations compared with GCB lymphomas (MYD88 23%; CD79B 10%) (P < .01). The ABC subtype frequently displayed cMYC/BCL2 coexpression (76% vs 18% GCB; P < .001) and HLA-II loss (48% vs 10% GCB; P < .001). PD-L1 expression and copy-number alterations were rare. All lymphomas were Epstein-Barr virus-negative. Our data suggest molecular profiling as a potent tool for detecting prognostic subgroups in PSDLBCL, exposing links to known relapse/dissemination sites. The ABC subgroup's MCD genetic features, shared with lymphomas at other nonprofessional lymphoid sites, make them potential candidates for targeted B-cell and toll-like receptor signaling therapy.

Head and neck ultrasound training improves the diagnostic performance of otolaryngology residents.

Objective: Surgeon-performed head and neck ultrasound (US) is increasingly used among otolaryngologists in office-based and surgical settings. However, it is unknown how formal US training affects otolaryngology residents' diagnostic workup of patients with cervical pathology. This study examined how a formal US course for residents affected their outpatient clinic US performance and diagnostic accuracy. Methods: We conducted a randomized cross-over trial, where 13 otolaryngology residents participated in a 6-h formal US course. Participants were randomized to perform head and neck US on four patient cases before and after completing the course. Eight patients with and without neck pathology were invited to participate as test cases. The ultrasound examinations were video recorded and anonymized before two consultants rated the US performance using the Objective Structured Assessment of Ultrasound Skills (OSAUS) scale. Otolaryngology residents wrote an ultrasound report with a diagnosis based on their US examination, which was used to calculate the specificity and sensitivity. Results: We found a statistically significant difference in the OSAUS score before compared to after the hands-on training (p = .035). The diagnostic accuracy also increased from 62% before the course to 75% after the course (p = .02). Specificity increased from 54% prior to the course to 62% following the course, and sensitivity increased from 64% prior to the course to 79% following the course. The intraclass correlation coefficient with "absolute agreement" was 0.63. Conclusion: This study demonstrates that short, formal ultrasound training can improve otolaryngology residents' ultrasound skills and diagnostic accuracy in an outpatient clinic setting. Lay summary: This study looks at the change of otolaryngology residents' diagnostic workup of patients after they take a formal ultrasound course and shows that they get better at using ultrasound and make more accurate diagnoses if they take a formal course. Level of Evidence: Level 2.

Impact of tumor subsite on survival outcomes in oral squamous cell carcinoma: A retrospective cohort study from 2000 to 2019.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is responsible for high morbidity and mortality worldwide. Although the oral cavity encompasses different anatomical subsites, it is unclear whether subsite localization of carcinoma influences outcome. METHODS: This retrospective cohort study examined overall survival (OS), recurrence-free survival (RFS) and local recurrence-free survival (L-RFS) at different subsites by Kaplan-Meier survival curves. Cox proportional hazards regression analysis was performed to investigate the impact of subsite on overall death, locoregional recurrence, and local recurrence. RESULTS: The cohort included 1702 patients treated with curative intent for OSCC according to standardized national guidelines. The 5-year OS was superior in oral tongue to retromolar trigone as well as in both oral tongue and floor-of-mouth (FOM) compared to tumors involving multiple locations. The 3-year RFS in oral tongue and FOM was superior to tumors involving multiple locations, and in FOM compared to retromolar trigone. The 3-year L-RFS in oral tongue and FOM was higher than gingiva, retromolar trigone and tumors involving multiple locations. Adjusting for relevant covariables using oral tongue as reference, tumors involving multiple locations was the only category presenting higher risk for locoregional recurrence, while risk of local recurrence was higher in gingiva, retromolar trigone, hard palate and to tumors involving multiple locations. The study found no difference in risk of death between subsites. CONCLUSION: The study found differences in survival outcomes between subsites. After adjusting for covariables, subsite mainly had significant impact on local recurrence, with no distinct pattern of influence on overall death or locoregional recurrence.

Fractional exhaled nitric oxide-a possible biomarker for risk of obstructive sleep apnea in snorers.

STUDY OBJECTIVES: Airway inflammation in patients with obstructive sleep apnea (OSA) has been described and can be assessed by measuring the biomarker fractional exhaled nitric oxide (FeNO). In this pilot study, we investigated FeNO measurements in identification of OSA among persons with snoring. METHODS: In this study we aimed to investigate (1) if FeNO could be used in screening for OSA, (2) if daytime sleepiness correlated to FeNO levels, and (3) whether asthma affected FeNO levels. Persons with snoring were prospectively included in three primary care ear, nose, and throat clinics. Patients underwent spirometry, FeNO tests, and partial polygraphy. They filled out questionnaires on sinonasal and asthma symptoms, daytime sleepiness, and quality of life. Current smokers, patients with upper airway inflammatory conditions, and patients treated with steroids were excluded. RESULTS: Forty-nine individuals were included. Median apnea-hypopnea index was 11.4, mean age was 50.9 years, and 29% were females. OSA was diagnosed in 73% of the patients of whom 53% had moderate-severe disease. Patients with moderate-severe OSA had significantly higher FeNO counts than patients with no or mild OSA (P = .024). Patients younger than 50 years with a FeNO below 15 had the lowest prevalence of moderate-severe OSA. No correlation was found between FeNO measurements and daytime sleepiness, and asthma did not affect FeNO levels. CONCLUSIONS: We found a low prevalence of moderate-severe OSA in persons with snoring when FeNO and age were low. This might be considered in a future screening model, though further studies testing the FeNO cutoff level and the diagnostic accuracy are warranted. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: NO Measurements in Screening for Asthma and OSA, in Patients With Severe Snoring; URL: https://clinicaltrials.gov/study/NCT03964324; Identifier: NCT03964324. CITATION: Kiaer E, Ravn A, Jennum P, et al. Fractional exhaled nitric oxide-a possible biomarker for risk of obstructive sleep apnea in snorers. J Clin Sleep Med. 2024;20(1):85-92.

COVID-19 Rapid Antigen Tests With Self-Collected vs Health Care Worker-Collected Nasal and Throat Swab Specimens: A Randomized Clinical Trial.

Importance: Self- or health care worker (HCW)-collected nasal swab specimens are the preferred sampling method to perform rapid antigen testing for COVID-19, but it is debated whether throat specimens can improve test sensitivity. Objective: To compare the diagnostic accuracy of self- and HCW-collected nasal vs throat swab specimens for COVID-19 rapid antigen testing. Design, Setting, and Participants: This per-protocol multicenter randomized clinical trial was conducted from February 15 through March 25, 2022. The participants, individuals aged 16 years or older requesting a COVID-19 test for diagnostic or screening purposes, had 4 specimens collected for individual testing at 1 of 2 urban COVID-19 outpatient test centers in Copenhagen, Denmark. Interventions: Participants were randomized 1:1 to self-collected or HCW-collected nasal and throat swab specimens for rapid antigen testing. Additional HCW-collected nasal and throat swab specimens for reverse transcriptase-polymerase chain reaction (RT-PCR) were used as the reference standard. Main Outcomes and Measures: The primary outcome was sensitivity to diagnose COVID-19 of a self- vs HCW-collected nasal and throat specimen for rapid antigen testing compared with RT-PCR. Results: Of 2941 participants enrolled, 2674 (90.9%) had complete test results and were included in the final analysis (1535 [57.4%] women; median age, 40 years [IQR, 28-55 years]); 1074 (40.2%) had COVID-19 symptoms, and 827 (30.9%) were positive for SARS-CoV-2 by RT-PCR. Health care worker-collected throat specimens had higher mean sensitivity than HCW-collected nasal specimens for rapid antigen testing (69.4% [95% CI, 65.1%-73.6%] vs 60.0% [95% CI, 55.4%-64.5%]). However, a subgroup analysis of symptomatic participants found that self-collected nasal specimens were more sensitive than self-collected throat specimens for rapid antigen testing (mean sensitivity, 71.5% [95% CI, 65.3%-77.6%] vs 58.0% [95% CI, 51.2%-64.7%]; P < .001). Combining nasal and throat specimens increased sensitivity for HCW- and self-collected specimens by 21.4 and 15.5 percentage points, respectively, compared with a single nasal specimen (both P < .001). Conclusions and Relevance: This randomized clinical trial found that a single HCW-collected throat specimen had higher sensitivity for rapid antigen testing for SARS-CoV-2 than a nasal specimen. In contrast, the self-collected nasal specimens had higher sensitivity than throat specimens for symptomatic participants. Adding a throat specimen to the standard practice of collecting a single nasal specimen could improve sensitivity for rapid antigen testing in health care and home-based settings. Trial Registration: ClinicalTrials.gov Identifier: NCT05209178.

Transoral Ultrasound in the Outpatient Clinic for the Diagnostic Work-Up of Oropharyngeal Cancer: A Feasibility Study.

Magnetic resonance imaging (MRI) is the preferred imaging modality for oropharyngeal cancers (OPCs), but it has difficulties distinguishing between small OPCs and unilateral tonsil hypertrophy. We hypothesized that surgeon-performed transoral ultrasound (US) could be used to accurately detect T-stage OPCs. We performed a single-center prospective diagnostic accuracy study including patients with suspected or biopsy-verified OPCs during outpatient appointments. All patients were offered transoral US and MRI. If transoral US could not be tolerated by the patient, transcervical US was performed. The primary outcome was the diagnostic accuracy of detecting OPCs with US compared to MRI, using histopathology as the reference standard. The secondary outcome was comparing the primary tumor diameters between US and MRI blinded to each other. Out of the 26 patients included in the study, 21 (81%) had OPCs. Transoral US could be performed in 21/21 and 1/5 patients with suspected palatine and lingual tonsil OPCs, respectively. Overall, US diagnostic accuracy was 92%, compared to 81% with MRI (p = 0.37). US and MRI had a high correlation between tumor diameters in the anteroposterior diameter (R = 0.80, p < 0.001), corresponding to the depth axis on US. In conclusion, this small study showed the promise and feasibility of transoral US to improve the initial clinical evaluations of patients with suspected OPCs.

Transoral robotic surgery - time for consensus on pain assessment. A review.

BACKGROUND: In Head and Neck surgery Transoral Robotic Surgery (TORS) is evolving as a key treatment option for benign and malignant lesions in the oropharynx. Even so, postoperative pain is one of the primary early complaints following TORS. Well established evidence-based procedure specific pain treatment guidelines are available for a variety of other surgical specialties. However, there are no guidelines for TORS. AIM: This review describes the available data of early pain intensity following TORS during rest and procedure related activity. METHODS: Literature concerning pain in the immediate postoperative phase following TORS were obtained from two literature databases. RESULTS: Most data on pain intensity following TORS are based upon a numeric rating scale, e.g. the Visual Analogue Scale and/or analgesic demands. Only one randomized clinical trial is available reflecting that the literature is mainly based on retrospective and a few prospective studies. Only one study analyzed pain during relevant functionality, i.e. swallowing. Overall, the studies suffer from a non-standardized approach and there is a need for transparent information concerning the timing of pain ratings and methodology. CONCLUSIONS: The evidence for optimal pain control is limited, particularly during surgical relevant activity. Postoperative pain rating during activity is a fundamental element in pain trials in order to enhance recovery thereby calling for future consensus on assessment methodology.

Why in hospital following transoral robotic lingual tonsillectomy?

BACKGROUND: The reported hospital length of stay (LOS) following transoral robotic surgery lingual tonsillectomy (TORS-L) is variable, with limited understanding of the factors requiring hospitalization and no evidence-based criteria for discharge. AIMS/OBJECTIVES: This observational cohort study investigated factors hindering discharge following TORS-L in a well-defined postoperative care program. METHODS: Patients were included between August 2020 and October 2022. A discharge scheme was filled out twice daily, specifying the factor(s) for hospitalization among patients undergoing TORS-L. This trial was a sub-investigation of a national multicentre randomized clinical trial (RCT) testing the efficiency of high-dose dexamethasone on postoperative pain control. Participation in the RCT demanded admission to the fourth postoperative day as dexamethasone/placebo was given intravenously in repeated dosages till day 4 postoperatively. RESULTS: Eighteen patients were included in the analysis. The main factor for hospitalization was nutritional difficulties, while pain was a limiting factor for discharge only on the first postoperative 1-3 days. More than half of the patients could have potentially been discharged on postoperative day 2 when omitting the RCT treatment plan in the analysis. CONCLUSION: The study estimates that the majority of patients may be discharged on postoperative day 2 following TORS-L.

The effect of dexamethasone on functional pain following Transoral Robotic Surgery: a randomized double blinded clinical trial.

BACKGROUND: Pain is prevalent after most TransOral Robotic Surgery (TORS) procedures and may limit function i.e. swallowing. Currently, there is limited knowledge regarding optimal pain treatment in TORS. AIMS/OBJECTIVES: This clinical trial randomized patients to either a high-dose dexamethasone or low-dose dexamethasone treatment in addition to a multimodal basic analgesic protocol. The aim of the trial was to investigate the pain intensity during rest and swallowing using the Visual Analogue Scale (VAS) after TORS lingual tonsillectomy. Secondary outcomes were acceptable food consistency, nausea, vomiting, opioid rescue usage, length of hospitalization, feeding tube placements, readmissions, blood glucose levels and postoperative complications. METHODS: The trial was conducted between August 2020 and October 2022. Eligible patients were patients scheduled for TORS-L treatment of obstructive sleep apnea syndrome or as part of the diagnostic work-up of head and neck carcinoma of unknown primary. RESULTS: Eighteen patients were and randomized 1:1. There were overall no significant differences between groups in the reported VAS scores during rest or swallowing (p ≥ .05). Overall, there were no differences in the secondary outcomes. CONCLUSION: There were no differences in the pain intensity in the two treatment groups allocated to a basic multimodal analgesic package and either high-dose dexamethasone or low-dose dexamethasone treatment. The trial is the first RCT to include pain measurement during a procedure-relevant activity, thus creating a platform for future recovery studies.

Clinical implication of genetic intratumor heterogeneity for targeted therapy in head and neck cancer.

BACKGROUND: Genomic profiling is increasingly used both in therapeutic decision-making and as inclusion criteria for trials testing targeted therapies. However, the mutational landscape may vary across different areas of a tumor and intratumor heterogeneity will challenge treatments or clinical decisions based on single tumor biopsies. The purpose of this study was to assess the clinical relevance of genetic intratumor heterogeneity in head and neck squamous cell carcinomas (HNSCC) using the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT). MATERIALS AND METHODS: This prospective study included 33 whole tumor specimens from 28 patients with primary or recurrent HNSCC referred for surgery. Three tumor blocks were selected from central, semi-peripheral, and peripheral positions, mimicking biopsies in three different locations. Genetic analysis of somatic copy number alterations (SCNAs) was performed on the three biopsies using Oncoscan, focusing on 45 preselected HNSCC genes of interest. Clinical relevance was assessed using the ESCAT score to investigate whether and how treatment decisions would change based on the three biopsies from the same tumor. RESULTS: The SCNAs identified among 45 preselected genes within the three tumor biopsies derived from the same tumor revealed distinct variations. The detected discrepancies could potentially influence treatment approaches or clinical decisions in 36% of the patients if only one tumor biopsy was used. Recurrent tumors exhibited significantly higher variation in SCNAs than primary tumors (p = .024). No significant correlation between tumor size and heterogeneity (p = .7) was observed. CONCLUSION: In 36% of patients diagnosed with HNSCC, clinically significant intratumor heterogeneity was observed which may have implications for patient management. This finding substantiates the need for future studies that specifically investigate the clinical implications associated with intratumor heterogeneity.

Liquid biopsies in thyroid cancers: a systematic review and meta-analysis.

Thyroid cancer (TC) represents the most common endocrine malignant tumor. Liquid biopsy has been suggested as a new and accurate biomarker in cancer. This systematic review analyzes the existing literature on circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), cell-free DNA integrity index (cfDI), and their potential as biomarkers for TC, including the subtypes: differentiated (papillary and follicular), medullary, and anaplastic. A systematic search was performed in PubMed, Embase, and Cochrane databases for published articles in English between 1 January 1970 and 6 September 2022 (PROSPERO: CRD42022358592). The literature search generated a total of 635 articles. In total, 36 articles were included (patients = 2566). Four studies reported that higher levels of CTCs were associated with metastases and worse prognosis. Nineteen studies found the presence of mutated ctDNA in TC patients. The diagnostic accuracy in detecting BRAFV600E as ctDNA was determined in 11 studies regarding papillary TC. The pooled sensitivity, specificity, and diagnostic odds ratio were estimated at 56% (95% CI 36-74), 91% (95% CI 84-95) and 12 (95% CI 4.09-33.11), respectively. Four studies concluded that the cfDI was higher in patients with TC compared to benign thyroid lesions and healthy controls. The detection of CTCs, ctDNA, and cfDI may have a potential prognostic value in TC in relation to diagnosis, disease progression, and treatment efficacy. Despite the promising potential of CTCs, ctDNA, and cfDI in TC management, limitations hinder direct comparison and generalization of findings. Standardized methodologies, larger patient cohorts, and a consensus on relevant markers are needed to validate their clinical applicability and enhance TC management.

Urokinase-Type Plasminogen Activator Receptor (uPAR) Expression and [64Cu]Cu-DOTA-AE105 uPAR-PET/CT in Patient-Derived Xenograft Models of Oral Squamous Cell Carcinoma.

PURPOSE: [64Cu]Cu-DOTA-AE105 urokinase-type plasminogen activator receptor (uPAR)-PET/CT is a novel and promising imaging modality for cancer visualization, although it has not been tested in head and neck cancer patients nor in preclinical models that closely resemble these heterogenous tumors, i.e., patient-derived xenograft (PDX) models. The aim of the present study was to establish and validate oral squamous cell carcinoma (OSCC) PDX models and to evaluate [64Cu]Cu-uPAR-PET/CT for tumor imaging in these models. PROCEDURES: PDX flank tumor models were established by engrafting tumor tissue from three patients with locally advanced OSCC into immunodeficient mice. [64Cu]Cu-DOTA-AE105 was injected in passage 2 (P2) mice, and [64Cu]Cu-uPAR-PET/CT was performed 1 h and 24 h after injection. After the last PET scan, all animals were euthanized, and tumors dissected for autoradiography and immunohistochemical (IHC) staining. RESULTS: Three PDX models were established, and all of them showed histological stability and unchanged heterogenicity, uPAR expression, and Ki67 expression through passages. A significant correlation between uPAR expression and tumor growth was found. All tumors of all models (n=29) showed tumor uptake of [64Cu]Cu-DOTA-AE105. There was a clear visual concordance between the distribution of uPAR expression (IHC) and [64Cu]Cu-DOTA-AE105 uptake pattern in tumor tissue (autoradiography). No significant correlation was found between IHC (H-score) and PET-signal (SUVmax) (r=0.34; p=0.07). CONCLUSIONS: OSCC PDX models in early passages histologically mimic donor tumors and could serve as a valuable platform for the development of uPAR-targeted imaging and therapeutic modalities. Furthermore, [64Cu]Cu-uPAR-PET/CT showed target- and tumor-specific uptake in OSCC PDX models demonstrating the diagnostic potential of this modality for OSCC patients.