Diagnostic Value of Preoperative uPAR-PET/CT in Regional Lymph Node Staging of Oral and Oropharyngeal Squamous Cell Carcinoma: A Prospective Phase II Trial.

The detection of lymph node metastases is a major challenge in oral and oropharyngeal squamous cell carcinoma (OSCC and OPSCC). 68Ga-NOTA-AE105 is a novel positron emission tomography (PET) radioligand with high affinity to urokinase-type plasminogen activator receptor (uPAR), a receptor expressed on the surfaces of tumor cells. The aim of this study was to investigate the diagnostic value of uPAR-PET/CT (computerized tomography) in detecting regional metastatic disease in patients with OSCC and OPSCC compared to the current imaging work-up. In this phase II trial, patients with OSCC and OPSCC referred for surgical treatment were prospectively enrolled. Before surgery, 68Ga-NOTA-AE105 uPAR-PET/CT was conducted, and SUVmax values were obtained from the primary tumor and the suspected lymph nodes. Histology results from lymph nodes were used as the standard of truth of metastatic disease. The diagnostic values of 68Ga-uPAR-PET/CT were compared to conventional routine preoperative imaging results (CT and/or MRI). The uPAR expression in resected primary tumors and metastases was determined by immunohistochemistry and quantified digitally (H-score). A total of 61 patients underwent uPAR-PET/CT. Of the 25 patients with histologically verified lymph node metastases, uPAR-PET/CT correctly identified regional metastatic disease in 14 patients, with a median lymph node metastasis size of 14 mm (range 3-27 mm). A significant correlation was found between SUVmax and the product of the H-score and tumor depth (r = 0.67; p = 0.003). The sensitivity and specificity of uPAR-PET/CT in detecting regional metastatic disease were 56% and 100%, respectively. When added to CT/MRI, uPAR-PET was able to upstage 2/11 (18%) of patients with occult metastases and increase the sensitivity to 64%. The sensitivity and specificity of 68Ga-NOTA-AE105 uPAR-PET/CT were equivalent to those of CT/MRI. The significant correlation between SUVmax and uPAR expression verified the target specificity of 68Ga-NOTA-AE105. Despite the target specificity, the sensitivity of imaging is too low for nodal staging and it cannot replace neck dissection.

Enhanced recovery after microvascular reconstruction in head and neck cancer - A prospective study.

Objectives: Patients undergoing microvascular reconstruction after head and neck cancer typically have several comorbidities, and the procedures are often followed by complications and prolonged hospitalization. Consequently, the application of enhanced recovery after surgery (ERAS) for these patients undergoing microvascular reconstruction has gained attention in recent years. ERAS is a peri- and postoperative care concept that has repeatedly shown beneficial results for a wide variety of surgical procedures, including microvascular reconstruction. This study presents the results after the introduction of our ERAS protocol for head and neck cancer reconstruction. Methods: We prospectively treated 30 consecutive patients according to our ERAS protocol from June 2019 to December 2020 and compared the results of the treated patients with those of patients treated with our traditional recovery after surgery (TRAS) protocol. We are based on our ERAS protocol on the following core elements of recovery: improved patient information, goal-directed fluid therapy, minimally invasive surgery, opioid-sparing multimodal analgesia, early ambulation, and pre-defined functional discharge criteria. Results: The baseline characteristics of the groups were comparable. The ERAS group had a significantly shorter length of stay (13.1 vs. 20.3 days, p < 0.001), significantly shorter time to ambulation (3.0 days vs. 6.4 days, p < 0.001), shorter time to removal of nasogastric tube (13.3 days vs. 22.7 days, p = 0.05), and fewer tracheostomies performed (10% vs. 90%, p < 0.001). There were no differences in complications, flap survival, or 30-day re-admissions between the two groups. Conclusion: The introduction of ERAS in patients with head and neck cancer undergoing microvascular reconstruction seems safe and results in improved recovery. Level of evidence: 3.

Nasal vestibule squamous cell carcinoma: a population-based cohort study from DAHANCA.

BACKGROUND: Cancer of the nasal vestibule is a rare type of malignancy dominated by squamous cell carcinoma (SCC), and with poor survival. The treatment is either radiotherapy, surgery or a combination of both. Previous studies have shown a 5-year disease-specific survival of 74% and overall survival (OS) of 50%.Our objective was to describe the consecutive cohort of patients diagnosed with SCC of the nasal vestibule in Denmark from 2008 until 2018 and evaluate prognostic factors and treatment outcome using locoregional failure (LRF), disease-specific mortality (DSM), and OS as endpoints. METHODS: All patients diagnosed with SCC of the nasal vestibule from 2008 until 2018 were identified in the nationwide clinical database, DAHANCA and were followed for LRF and death (DSM and OS) until March 2021. OS was analysed using Kaplan-Meier estimator, and cumulative incidence of LRF and DSM were analysed using the Aalen-Johansen estimator. Analysis of prognostic factors was performed using Cox proportional hazard models. RESULTS: A total of 162 patients were identified. The median age was 71 years and 54% were male. Disease stage at the time of diagnosis were stage I (70%), II (17%), III (2%) and IV (11%). Curatively intended treatment was performed in 146 patients (90%), of which treatment failure occurred in 42 patients (29%). Most failures occurred at the primary tumour site (64%). Cancer Patient Pathways recommended time to treatment was fulfilled in 71% of patients. The 5-year OS and DSM in patients treated with curative intent were 65% and 11%, respectively. Stage was a significant independent prognostic factor. No difference in LRF, DSM or OS were shown between the applied treatments. CONCLUSIONS: Stage is the main independent prognostic factor, and failure most commonly appear at the primary tumour site.

Days alive and out of hospital following transoral robotic surgery: Cohort study of 262 patients with head and neck cancer.

BACKGROUND: Days alive and out of hospital (DAOH) is a validated outcome in clinical trials, since it reflects procedure-associated morbidity and mortality. Transoral robotic surgery (TORS) has become a widely adopted procedure with increasing demand for knowledge and data on morbidity. METHODS: Retrospective single-center assessment of a prospective TORS database comprising patients treated for malignancy between 2013 and 2018 using DAOH to describe procedure- and disease-related morbidity the first 12-postoperative months. RESULTS: For 262 patients, median DAOH365 was 357 days (IQR 351-360). Indications for TORS were (i) primary curative resection (61%), (ii) salvage resection (15%), and (iii) diagnostic work-up of cancer of unknown primary in the head and neck (24%). Median DAOH365 was 359 days (IQR 351-361 days), 348 days (IQR 233-355), and 357 days (351-361), respectively. Pneumonia had the highest impact in DAOH365 reduction. CONCLUSION: Total median DAOH365 after TORS was 357 days. The main cause leading to DAOH365 reduction was pneumonia.

Long-term quality of life & functional outcomes after treatment of oropharyngeal cancer.

Functional and QoL outcomes were compared longitudinally in a cohort of patients treated for oropharyngeal squamous cell carcinoma (OPSCC) with primary transoral robotic surgery (TORS) or radiotherapy (RT). Forty-four patients undergoing primary TORS (n = 31) or RT (n = 13) for any stage OPSCC were included. Only low-stage disease was treated with TORS. Functional outcomes were: salivary flow rate, image-based swallowing function, and a self-reported 10-point scale comparing current swallowing function to baseline (CvB scale). QoL was assessed with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30), Head & Neck Module (EORTC QLQ-HN35), and MD Anderson Dysphagia Inventory (MDADI). Shoulder impairment was assessed with Neck Dissection Impairment Index (NDII) and Oxford Shoulder Score (OSS). In the RT group, salivary flow rates had significantly declined at 12-month follow-up, with the biggest declines in QoL subscale scores recorded in the RT group for dry mouth and sticky saliva. Swallowing function on imaging studies was overall good, with no severe dysphagia within 1 year although, both treatment groups showed significant deterioration relative to baseline at the 12-month follow-up with increased DIGEST scores and pharyngeal retention. Shoulder impairment was rare at 1 year in both groups. A comprehensive examination of this cohort treated for OPSCC showed overall good functional and QoL outcomes 1 year after treatment. However, persistent impairment was seen in both groups with regards to swallowing function. In the TORS group, at 12-months follow-up, the QoL questionnaires showed worse scores in only one subscale (sticky saliva).

Microvascular reconstruction in head and neck cancer - basis for the development of an enhanced recovery protocol.

INTRODUCTION: Microvascular reconstructions after head and neck cancer are among the most complicated procedures in plastic surgery. Postoperative complications are common, which often leads to prolonged hospital stay. Enhanced recovery after surgery (ERAS) is a peri- and postoperative care concept with the aim of achieving pain- and risk-free surgery. It has been previously established as superior to conventional care for a wide variety of procedures, including microsurgical procedures such as reconstructions of the breast. Several ERAS protocols for microvascular head and neck cancer reconstructions have been proposed, although most of these are based on extrapolated evidence from different surgical specialties. Results from the implementation of ERAS for these procedures are inconsistent. METHODS: The current study investigates our clinical experience of head and neck cancer reconstruction for the period of 2014-2016 with the aim of establishing a list of functional discharge criteria. By combining these with the current published knowledge on the subject, we developed an ERAS protocol. RESULTS: We performed 89 microvascular procedures in the study period, of which 58 were in the oral cavity/sinuses and 31 were laryngopharyngeal. Most cases were squamous cell carcinoma (89%). The average LOS was 20.3 days in both groups. Postoperative complications included infection (37%), 30-days re-operations (19%), and re-admissions (17%). Furthermore, we identified the following discharge criteria: adequate pain relief, ambulation, sufficient nutritional intake, normal infection-related blood parameter results and absence of fever, bowel function, and closure of tracheostomy. CONCLUSION: Based on our retrospective analysis and identified discharge criteria, we present an approach to develop an ERAS protocol for microvascular reconstruction after head and neck cancer.

Diagnostic flexible pharyngo-laryngoscopy: development of a procedure specific assessment tool using a Delphi methodology.

PURPOSE: Proper training and assessment of skill in flexible pharyngo-laryngoscopy are central in the education of otorhinolaryngologists. To facilitate an evidence-based approach to curriculum development in this field, a structured analysis of what constitutes flexible pharyngo-laryngoscopy is necessary. Our aim was to develop an assessment tool based on this analysis. METHODS: We conducted an international Delphi study involving experts from twelve countries in five continents. Utilizing reiterative assessment, the panel defined the procedure and reached consensus (defined as 80% agreement) on the phrasing of an assessment tool. RESULTS: FIFTY PANELISTS COMPLETED THE DELPHI PROCESS. THE MEDIAN AGE OF THE PANELISTS WAS 44 YEARS (RANGE 33-64 YEARS). MEDIAN EXPERIENCE IN OTORHINOLARYNGOLOGY WAS 15 YEARS (RANGE 6-35 YEARS). TWENTY-FIVE WERE SPECIALIZED IN LARYNGOLOGY, 16 WERE HEAD AND NECK SURGEONS, AND NINE WERE GENERAL OTORHINOLARYNGOLOGISTS. AN ASSESSMENT TOOL WAS CREATED CONSISTING OF TWELVE DISTINCT ITEMS.: Conclusion The gathering of validity evidence for assessment of core procedural skills within Otorhinolaryngology is central to the development of a competence-based education. The use of an international Delphi panel allows for the creation of an assessment tool which is widely applicable and valid. This work allows for an informed approach to technical skills training for flexible pharyngo-laryngoscopy and as further validity evidence is gathered allows for a valid assessment of clinical performance within this important skillset.

Transoral robotic surgery for the management of head and neck squamous cell carcinoma of unknown primary.

CONCLUSION: The addition of transoral robotic surgery (TORS) in the diagnostic management of patients classified with head and neck squamous cell carcinoma of unknown primary (SCCUP) is promising and appears to improve detection rates of the primary tumour. The approach presented in this first Scandinavian study could potentially minimize the radiation field to the pharyngeal axis in patients with identified primary tumours. OBJECTIVES: The aim of the study was to investigate whether bilateral lingual tonsillectomy performed with TORS is feasible, and whether it could improve the detection rates of primary tumours in patients diagnosed and classified as having SCCUP. METHODS: The study was retrospective and included 13 patients with SCCUP who were referred to TORS between October 2013 and January 2015. All 13 patients had previously undergone a full investigation programme following the national guidelines including whole-body PET/CT, examination in general anaesthesia, including random biopsies of the base of the tongue and bilateral palatine tonsillectomy without identification of the primary tumour. RESULTS: The primary tumour was identified by TORS in seven of the 13 patients (54%) at the lingual tonsils. Human papillomavirus DNA and p16 were positive in all identified primary tumour specimens and in the corresponding lymph node metastases.