The prognostic effect of radiological extranodal extension in HPV-positive oropharyngeal squamous cell carcinomas: a retrospective cohort analysis.

PURPOSE: Radiological extranodal extension (rENE) is a well-known negative prognosticator in head and neck squamous cell carcinoma (HNSCC). However, controversy remains regarding the prognostic effect of rENE in HPV-positive oropharyngeal SCCs (OPSCC). This single-center retrospective cohort analysis assessed the prognostic role of rENE in an HPV + OPSCC population and tried to validate a recently proposed modification of the TNM8 N-classification. METHODS: 129 patients with HPV + OPSCC, of whom 106 cN + patients, were included. Radiological imaging (CT, MRI or both) was reanalyzed by a senior head and neck radiologist. Overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRFS), and disease-specific survival (DSS) were evaluated. Cox proportional hazard models were used for estimating hazard ratios (HR). RESULTS: A non-significant trend towards better outcomes in the rENE- group, as compared to the rENE + population, was observed for 5 year OS [80.99% vs 68.70%, HR: 2.05, p = 0.160], 5 year RFS [78.81% vs 67.87%, HR: 1.91, p = 0.165], 5 year DFS [77.06% vs 60.16%, HR: 2.12, p = 0.0824] and 5 year DSS [88.83% vs 81.93%, HR: 2.09, p = 0.195]. OS declined with ascending levels of rENE (p = 0.020). Multivariate analysis identified cT-classification and smoking as independent negative predictors for OS/DFS. The proposed modification of the TNM8 N-classification could not be validated. CONCLUSIONS: Although rENE could not be identified as an independent negative prognosticator for outcome in our HPV + OPSCC population, outcomes tend to deteriorate with increasing rENE.

Prospective Evaluation and Validation of the Laryngoscore and the mini-Laryngoscore.

OBJECTIVE: The Laryngoscore was described in 2014 as a practical preoperative assessment tool to predict difficult laryngeal exposure (DLE) during transoral approaches to the larynx. In 2019 the authors proposed a version with a reduced number of variables, called the mini-Laryngoscore. We aim to critically appraise and externally validate these two tools and if needed and possible, to optimize these tools. METHODS: 103 consecutive patients who underwent a microlaryngoscopy between November 2017 and June 2020 at the Leuven University Hospitals were prospectively included and subjected to a presurgical evaluation of 15 parameters and a peroperative scoring of the anterior commissure visualization. Subsequent analysis focused on the concordance of our findings with those of Piazza et al., the discriminatory ability of the test, and the validity of the included items. We then evaluated a modified prediction tool. RESULTS: Of 103 patients, 18 (17.5%) had DLE. The Laryngoscore and mini-Laryngoscore predicted this with a "good" C-index of respectively 0.727 (95%CI: 0.608-0.846) and 0.714 (95%CI: 0.605-0.823). A newly created prediction tool including only three parameters (Interincisors gap, upper jaw dental status and previous treatments) showed a better discriminatory ability (C-index = 0.835, 95%CI: 0.726-0.944) than the original Laryngoscore, a finding that needs further external validation. CONCLUSION: The original Laryngoscore and the mini-Laryngoscore displayed a good discriminative ability. Some parameters can be left out of the Laryngoscore without losing discrimination. An even better prediction model seems possible, using a weighted sum of selected predictor variables and by using the parameters in their continuous form. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:1807-1812, 2024.

Exploring long-term responses to immune checkpoint inhibitors in recurrent and metastatic head and neck squamous cell carcinoma.

OBJECTIVES: Immune checkpoint inhibitors (ICI) have introduced a new era in the treatment of recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Optimal duration for ICI therapy is still unclear and the long-term outcomes and toxicity in patients responding to these therapies warrant further exploration. This study attempts to identify the clinical and biological determinants of a durable response and evaluate outcomes following ICI treatment discontinuation. MATERIALS AND METHODS: A retrospective review of 181 patients treated with ICI for R/M HNSCC was conducted. Long-term responders were defined as patients who sustained disease control at least two years after initiating ICI therapy. We compared clinical and biological characteristics associated with these long-term responders against the broader treatment population. RESULTS: 10 % of R/M HNSCC patients treated with ICIs demonstrated a durable long-term response. Only three relapses (16 %) occurred after discontinuing ICI treatment in this subset, with a median follow-up of 52 months. Upon retreatment with ICI, two attained a documented response. Extended ICI response was observed even with < 2 years of treatment. 74 % of long-term responders experienced immune-related adverse events (irAEs), 37 % of which severe irAEs. Hypothyroidism was the most frequently reported irAEs. The predictive potential of systemic inflammation indices for clinical response appears to be limited. CONCLUSIONS: ICI present an optimistic avenue for HNSCC patients, offering substantial long-term responses. The study suggests that a two-year treatment could be optimal and irAEs, although common, are typically mild.

Leukocyte- and platelet-rich fibrin in endoscopic endonasal skull base reconstruction: study protocol for a multicenter prospective, parallel-group, single-blinded randomized controlled non-inferiority trial.

BACKGROUND: Recent advances in endoscopic endonasal transsphenoidal approaches (EETA) for skull base lesions have resulted in a significant increase in extent and complexity of skull base defects, demanding more elaborate and novel reconstruction techniques to prevent cerebrospinal fluid (CSF) leakage and to improve healing. Currently, commercially available fibrin sealants are often used to reinforce the skull base reconstruction. However, problems have been reported regarding hypersensitivity reactions, efficacy, and costs. This trial aims to investigate autologous leukocyte- and platelet-rich fibrin (L-PRF) membranes as an alternative for commercially available fibrin glues in EETA-related skull base reconstruction reinforcement. METHODS/DESIGN: This multicenter, prospective randomized controlled trial aims to demonstrate non-inferiority of L-PRF membranes compared to commercially available fibrin sealants in EETA cases (1) without intra-operative CSF-leak as dural or sellar floor closure reinforcement and (2) in EETA cases with intra-operative CSF-leak (or very large defects) in which a classic multilayer reconstruction has been made, as an additional sealing. The trial includes patients undergoing EETA in three different centers in Belgium. Patients are randomized in a 1:1 fashion comparing L-PRF with commercially available fibrin sealants. The primary endpoint is postoperative CSF leakage. Secondary endpoints are identification of risk factors for reconstruction failure, assessment of rhinological symptoms, and interference with postoperative imaging. Additionally, a cost-effectiveness analysis is performed. DISCUSSION: With this trial, we will evaluate the safety and efficacy of L-PRF compared to commercially available fibrin sealants. TRIAL REGISTRATION: ClinicalTrials.gov NCT03910374. Registered on 10 April 2019.

Vagal paragangliomas.

PURPOSE OF REVIEW: A vagal paraganglioma is a rare head and neck tumor arising from the paraganglionic tissue within the perineurium of the vagus nerve, anywhere along the course of the nerve. Due to its proximity to the internal carotid artery, the internal jugular vein and the lower cranial nerves, this disorder poses significant diagnostic and therapeutic challenges. The diagnostic workup and management keep on evolving. RECENT FINDINGS: This article gives a concise update of the clinical spectrum and the current state-of-the-art diagnostic workup and management of vagal paraganglioma. SUMMARY: Every patient with suspected vagal paraganglioma needs to be evaluated by a multidisciplinary team. The management strategy is selected depending on the growth rate of the tumor, the age and fitness of the patient, the number of affected cranial nerves, the metabolic activity of the paraganglioma, and the eventual multicentricity. An algorithm guiding the clinician through the different treatment options is presented.

Remote-access robotic thyroidectomy: A systematic review.

BACKGROUND: Recently, robotic surgery has been introduced as a new surgical approach to the thyroid. OBJECTIVES: The primary objective of this systematic review is to critically examine safety and feasibility of the different robotic approaches. METHODS: The literature on robotic thyroidectomy was systematically reviewed. Primary endpoints were surgery duration, length of hospital stay, complications, postoperative pain and cosmetic satisfaction. RESULTS: Sixty-eight studies with a total of 14433 patients were included. Depending on the robotic approach used, operative duration ranged between 89 and 230 min and hospitalisation stay between 0.1 and 5.6 days. Complication rates varied between 7.3% and 29%. Postoperative pain visual analogue scores (VAS) ranged from 0.6 to 4.71. CONCLUSION: Robotic thyroidectomy results in high cosmetic satisfaction and quality of life. No differences in complication rates between robotic and traditional approaches are observed, supporting safety and feasibility of these robotic techniques.

Cervical squamous cell carcinoma of unknown primary: Oncological outcomes and prognostic factors.

Background/Objectives: Cervical squamous cell carcinoma of unknown primary (SCCUP) is a rare entity within head and neck cancer and both treatment regimens as well as identified potential predictors for oncological outcomes vary between published series. In this study, we evaluated oncological outcomes and identified potential prognostic factors for outcome. Patients and methods: This retrospective monocentric cohort study includes 82 SCCUP patients diagnosed and treated between January 2000 and June 2021. Overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS) and locoregional recurrence-free survival (LRFS) were evaluated. The Cox proportional hazards model was used to analyze the prognostic effect of patient and tumor characteristics on oncological outcomes. Results: Five year OS, DSS, DFS and LRFS were respectively 53.9%, 72.2%, 68.9% and 67.3%. The p16 status was evaluated in 55 patients with 40% being p16 positive. On univariable analysis, p16 negative SCCUPs had significantly worse survival and recurrence rates in the presence of clinical extranodal extension (cENE) (OS: p=0.0013, DSS: p=0.0099, DFS: p=0.0164, LRFS: p=0.0099) and radiological extranodal extension (rENE) (OS: p=0.0034, DSS: p=0.0137, DFS: p=0.0167, LRFS: p=0.0100). In p16 positive SCCUP patients, rENE had a significantly negative prognostic effect on DFS (p=0.0345) and LRFS (p=0.0367). Total group multivariate analysis identified rENE as an independent negative predictor for all oncological outcomes. The "number of positive lymph nodes" was a second independent predictor for DSS (p=0.0257) and DFS (p=0.0435). Conclusions: We report favorable oncological outcomes, comparable to previously published results. Although the presence of rENE seems associated with poor oncological outcomes, the differential effect of clinical, radiological and pathological ENE in both p16 positive and negative subgroups remain to be elucidated by further prospective research.

Transoral Robotic Surgery for Recurrent Tumors of the Upper Aerodigestive Tract (RECUT): An International Cohort Study.

BACKGROUND: Transoral robotic surgery (TORS) is an emerging minimally invasive surgical treatment for residual, recurrent, and new primary head and neck cancers in previously irradiated fields, with limited evidence for its oncological effectiveness. METHODS: A retrospective observational cohort study of consecutive cases performed in 16 high-volume international centers before August 2018 was conducted (registered at clinicaltrials.gov [NCT04673929] as the RECUT study). Overall survival (OS), disease-free survival, disease-specific survivals (DSS), and local control (LC) were calculated using Kaplan-Meier estimates, with subgroups compared using log-rank tests and Cox proportional hazards modeling for multivariable analysis. Maximally selected rank statistics determined the cut point for closest surgical resection margin based on LC. RESULTS: Data for 278 eligible patients were analyzed, with median follow-up of 38.5 months. Two-year and 5-year outcomes were 69.0% and 62.2% for LC, 71.8% and 49.8% for OS, 47.2% and 35.7% for disease-free survival, and 78.7% and 59.1% for disease-specific survivals. The most discriminating margin cut point was 1.0 mm; the 2-year LC was 80.9% above and 54.2% below or equal to 1.0 mm. Increasing age, current smoking, primary tumor classification, and narrow surgical margins (≤1.0 mm) were statistically significantly associated with lower OS. Hemorrhage with return to theater was seen in 8.1% (n = 22 of 272), and 30-day mortality was 1.8% (n = 5 of 272). At 1 year, 10.8% (n = 21 of 195) used tracheostomies, 33.8% (n = 66 of 195) used gastrostomies, and 66.3% (n = 53 of 80) had maintained or improved normalcy of diet scores. CONCLUSIONS: Data from international centers show TORS to treat head and neck cancers in previously irradiated fields yields favorable outcomes for LC and survival. Where feasible, TORS should be considered the preferred surgical treatment in the salvage setting.

Long-term follow-up of the inside-out technique for treatment of preauricular sinuses: observational study.

PURPOSE: This long-term follow-up study aims to externally validate the inside-out technique for surgical treatment of preauricular sinuses. METHODS: We analyzed the medical records of all patients who underwent the IO procedure at University Hospitals Leuven from 1 November 2005 to 30 November 2019 (N = 110). We were able to contact 77 of these 110 patients for a telephone interview, where we used a standardized questionnaire to evaluate recurrence, patient satisfaction and aesthetic result. RESULTS: We studied 110 patients (68 males, 77 females), resulting in 145 PAS (35 left, 40 right, 35 bilateral), with a median follow-up of 53 months. Fifteen PAS (10.3%) developed an early (< 4 weeks) postoperative complication (wound dehiscence, infection, abcedation, swelling). Two PAS (2 different patients) needed revision surgery because of recurrence, one after 15 months, the other after 4 years. The 5-year Kaplan-Meier recurrence-free percentage was 97.7%, equating to an estimated recurrence rate of 2.3%. Ninety-four percent was satisfied with the aesthetic result, giving 4 or 5 points on a 5-point Likert scale. CONCLUSIONS: This study was able to externally validate the IO technique for the treatment of PAS. The IO technique should be first choice, since it guarantees low recurrence rates, excellent aesthetic results, and good patient satisfaction.

A Retrospective Analysis of a Cohort of Patients Treated With Immune Checkpoint Blockade in Recurrent/Metastatic Head and Neck Cancer.

OBJECTIVE: The treatment approach of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has long been similar for all patients. Any difference in treatment strategy was only based on existing comorbidities and on preferences of the patient and the treating oncologist. The recent advance obtained with immune therapy and more specifically immune checkpoint blockade (ICB) has been a true game changer. Today, patients and physicians have a choice to omit chemotherapy. In a small subset of patients, ICB induces a very durable disease control. The subgroup of patients in which ICB without chemotherapy would be the preferential approach is still ill-defined. Yet, this evolution marks a major step towards a more personalized medicine in R/M HNSCC. MATERIALS AND METHODS: In this paper, we present a retrospective cohort study of a patient population that was treated with ICB in a single center and we analyze potential factors that are associated with outcome and may help to select patients for treatment with ICB. RESULTS: 137 consecutively treated patients were identified. Male gender and metastatic disease appeared to be associated with improved overall survival (OS). There was no correlation observed with age, number of previous treatment lines or immune target. CONCLUSION: Along with PD-L1 status defined by Combined Positive Score (CPS), clinical parameters such as site of recurrence and gender may help to define the optimal treatment strategy in R/M HNSCC.

Preclinical implementation of a steerable, Da Vinci Xi® compatible CO2 -laser fibre carrier for transoral robotic surgery (TORS): A cadaveric feasibility study.

INTRODUCTION: Monopolar electrocautery is the most common dissection and coagulation tool during transoral robotic surgery (TORS) but causes significant collateral tissue damage as opposed to CO2 laser. We aimed at combining both modalities in one robotic instrument arm. METHODS: We developed a steerable CO2 -laser fibre carrier serving as an add-on to the existing Endowrist® monopolar spatula of the Da Vinci Xi. Feasibility and safety were assessed in a preclinical setting. RESULTS: One radical tonsillectomy with monopolar cautery and three with the instrument prototype were performed in two cadavers by two surgeons. No serious prototype-related intra-operative difficulties were observed. Safe and efficient switching between energy sources proved possible in all simulated intra-operative bleeding events. Prototype use allowed for the identification of the majority of key anatomical structures and was scored favourably on NASA-TLX questionnaires. DISCUSSION: The reported prototype successfully combines the advantages of CO2 -laser with the advantages of TORS.

Transoral robotic surgery (TORS) using the da Vinci Xi: prospective analysis of feasibility, safety, and outcomes.

BACKGROUND: The da Vinci Xi system is not Food and Drug Administration approved for transoral robotic surgery (TORS), resulting in limited data. METHODS: This prospective study evaluates the feasibility, safety, and outcomes of Xi-TORS in an oncological setting. RESULTS: Sixty-one patients with head and neck cancer were consecutively included for Xi-TORS. Adequate exposure and macroscopically complete resection were achieved in 59 patients (success rate = 96.7%). Intraoperative difficulties and complications were encountered in 47.5% and 20.3% of patients, respectively. Postoperative hemorrhage occurred in 11.9%; no treatment-related deaths were encountered. Two-year overall survival and disease-specific survival were 90.5% and 95.6%, respectively. No long-term (>1 month) tracheotomies were necessary, and only two patients remained tube-feeding dependent. The functional baseline level was regained at 12 months for the MD Anderson Dysphagia Inventory and at 24 months for the Swallowing quality-of-life questionnaire. QLQ-H&N35-assessed QOL returned to baseline 6 months postoperatively. CONCLUSIONS: Xi-TORS is safe, feasible, and with high oncological and functional effectiveness.

Long-term outcome of a cohort of 272 patients undergoing sialendoscopy.

OBJECTIVES: To assess the cohort of patients undergoing sialendoscopic intervention for improvement of symptoms and gland-related quality of life at long-term follow-up. DESIGN: This is a retrospective review of medical records with a prospective follow-up by questionnaire. SETTING & PARTICIPANTS: All patients undergoing sialendoscopy at the University Hospitals Leuven Department of Otorhinolaryngology, Head and Neck Surgery between March 2008 and June 2020. MAIN OUTCOME MEASURES: The electronic files of the patients were searched for information about their sialendoscopic procedure and follow-up consultations. We also send the patients a questionnaire by mail to assess symptom control and gland-related quality of life at long-term follow-up. RESULTS: Two hundred seventy-two sialendoscopies were performed in 221 patients. Median follow-up time was 37 months. The sialendoscopies were performed in 130 patients for lithiasis, in 66 for stenosis, in 14 for recurrent parotitis of childhood, in 8 for recurrent sialadenitis of unknown origin and in 3 for radioiodine-induced sialadenitis. Complications occurred in 11 of 272 sialendoscopies (4%). Those were iatrogenic perforations, temporary lingual nerve paresthesia and swelling of the floor of the mouth. 53% of patients returned the questionnaire, for a total of 146 evaluable sialendoscopies. The majority of the responders indicated that sialendoscopy had improved their symptoms (83.6%). Salivary glands could be preserved in 89% of the responder group. The highest percentage of patients reporting residual symptoms was found in the RPC group (81.3%) and the lowest in the lithiasis group (16.2%). Besides age, no statistical differences in demographic and pathological features between the responder and non-responder groups were found, supporting generalisation of the responders' results to the entire cohort. CONCLUSIONS: This study confirms the good long-term outcomes of sialendoscopic interventions in patients with chronic sialadenitis of different aetiologies and a high rate of gland preservation.

Fourth Branchial Anomalies: Diagnosis, Treatment, and Long-Term Outcome.

Introduction: Fourth branchial anomalies, the rarest among anomalies of the branchial apparatus, often present diagnostic and therapeutic challenges. We evaluated the clinical presentation and radiographic features, the treatment and the long-term outcome of patients in this setting. Patients and Methods: Of 12 patients treated in the University Hospitals Leuven from 2004 until 2020, 12 variables were collected: date of birth, gender, age of onset of the symptoms, age at final diagnosis, presentation, laterality, previous procedures, diagnostic tools, treatment (open neck surgery, endoscopic laser excision, or combination), complications, recurrence, and period of follow-up. Descriptive statistics were calculated and results were compared to the existing literature. Results: The most common clinical manifestations were recurrent neck infections with and without abcedation. Definitive diagnosis using direct laryngoscopy, visualizing the internal sinus opening, was possible in all patients. A CT study revealed the typical features of fourth branchial anomalies in seven patients out of nine, an ultrasound study in five out of nine patients. All patients underwent open neck surgery. If this was insufficient, secondary endoscopic laser resection of the ostium at the apex of the piriform sinus was performed (n = 4). In eight patients a thyroid lobectomy was needed for safe complete resection. Postoperative complications were minimal and at long-term, none of the patients showed further recurrence. Average time of follow-up was 8.6 years. Conclusions: Direct laryngoscopy and CT are the most accurate diagnostic tools. Our recommended treatment schedule consists of complete excision of the sinus tract by open neck surgery as the primary treatment because this ensures the best results. In case of recurrence afterwards, endoscopic laser resection of the pharyngeal ostium solved the problem.

Salvage surgery for residual or recurrent laryngeal squamous cell carcinoma after (Chemo)radiotherapy: Oncological outcomes and prognostic factors.

Nonsurgical primary treatment of early and advanced laryngeal squamous cell carcinoma, employing radiotherapy with or without chemotherapy, is considered a standard of care in many centers throughout the world. When patients have persistent or recurrent disease after non-surgical treatment, salvage surgery is frequently the only remaining potentially curative treatment. Depending on the extent of the residual/recurrent disease, different surgical salvage options are at the surgeon's disposal. In selected cases with limited local disease, salvage transoral laser microsurgery, transoral robotic surgery and open partial laryngectomies can be employed to achieve cure while preserving laryngeal function. For more advanced cases total laryngectomy is necessary. Identifying situations with unacceptable results from surgical salvage may guide future therapies.

Endoscopic, Endonasal Transsphenoidal Surgery for Tumors of the Sellar and Suprasellar Region: A Monocentric Historical Cohort Study of 369 Patients.

BACKGROUND: The endoscopic endonasal transsphenoidal approach (EETA) is an established technique for the resection of a large variety of benign sellar and suprasellar lesions, mostly pituitary adenomas. It has clear advantages over the microscopic approach, like a superior close-up view of the relevant anatomy and the tumor-gland interface, an enlarged working angle, as well as an increased panoramic vision inside the surgical area. We have been performing the EETA for over a decade, and this study will focus on perioperative and postoperative outcomes and complications and their association with the learning curve. MATERIAL AND METHODS: All patients in our tertiary referral center (n = 369) undergoing an EETA for a lesion of the sellar and suprasellar region between January 1st 2008 and December 31st 2018 were included, and data were retrospectively retrieved from the electronic patient records. RESULTS: Median follow-up after surgery was 55 months. Pituitary adenomas (n = 322) were the most frequent pathology. Headache (43.4%) and loss of vision (29.3%) were the most common presenting symptoms. Median procedure duration was significantly longer during the initial 5 years (106 versus 79 minutes; p <0.0001), but incidence of peri- and postoperative CSF leaks in the early years was not significantly higher. Knosp grade >2 was associated with perioperative CSF leak (p =0.002), and perioperative CSF leak was associated with postoperative CSF leak (p <0.001). Almost all cases of meningitis were preceded by a postoperative CSF leak. In 22.4% of patients, tumor recurrence required additional therapy. Perioperative (iatrogenic) mortality was 0.8%. The overall hospital stay decreased over time from an average of 7 to 5 days, and the case load increased yearly (p =0.015). CONCLUSION: The EETA is an excellent technique with complication rates comparable to or even lower than those in large microsurgical series in the literature. EETA has a significant learning curve affecting the procedure duration. Throughout the first 10 years following the transition from the microscopic approach to the EETA in our cohort, the caseload increased and hospital stay was reduced, while no increase in peri- and postoperative complications was observed.

Introduction of a New Pathology Workup Protocol for Glottic Cancer Treated With Transoral Laser Microsurgery (TLM): Prospective Analysis of Oncological Outcomes and Matched Case-Control Study.

BACKGROUND/PURPOSE: The value of margin status after TLM for glottic cancer is debatable, due to difficulties in specimen orientation and margin analysis. To reduce these difficulties, we recently introduced a standardized protocol of oriented fixation of TLM specimens. This proved feasible and resulted in high margin evaluability rates and a decreased rate of false positive deep margins, when compared to a historical TLM cohort. For the patients whose specimens were processed according to this protocol, we prospectively analyzed oncological outcomes, identified prognostic factors and assessed the influence of the protocol introduction on outcomes compared with a historical TLM cohort. METHODS: Ninety-six patients with glottic malignancies treated with TLM were included. Resection specimens were processed according to the new protocol. Descriptive statistics and survival analyses were used to determine oncological outcomes. To assess the effect of the protocol introduction on outcomes, a matched-case-control analysis was performed, using a historical TLM-cohort as controls. The Cox proportional hazards model was used to analyze prognostic effects of patient and treatment characteristics, including the pathology protocol introduction, on overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS) and local recurrence-free survival (LRFS). RESULTS: Two-year outcomes were favorable: 88.5% OS, 97.0% DSS, and 87.6% LRFS. At multivariable analysis, the presence of multiple positive superficial margins was a negative prognosticator for OS (HR 4.102) and increasing cT classification proved a negative prognosticator for DFS (HR 2.828) and LRFS (HR 2.676). Matched case-control analysis did not reveal a significant difference in oncological outcomes between cohorts. Deep margin status had a strong differential effect for DFS (p-value for interaction = 0.0205) and for LRFS (p-value for interaction = 0.0176) between cohorts, indicating a prognostic effect of deep margin status on both outcomes in the current cohort, but not in the historical cohort. DISCUSSION/CONCLUSION: The introduction of a new standardized technique of oriented fixation of TLM specimens did not affect oncological outcomes when compared to a historical TLM cohort, but assigned a significant prognostic effect to deep margin status for DFS and LRFS, facilitating the decision making process with regards to planning of second-look procedures, administration of adjuvant radiotherapy or determination of follow-up intensity.

Current indications for adjuvant treatment following transoral laser microsurgery of early and intermediate laryngeal cancer.

PURPOSE OF REVIEW: This review summarizes the information in the literature on the indications for adjuvant therapy after transoral laser microsurgery (TLM) for early/intermediate stage laryngeal cancer. RECENT FINDINGS: A high rate of 'nonevaluable' margins after TLM significantly complicates decision-making concerning adjuvant therapy. However, consensus grows that second-look TLM in patients with multiple superficial and deep positive margins is more sensible than sending these patients systematically for adjuvant radiotherapy (RT). SUMMARY: The classical adagium: 'Failure to achieve negative margins indicates need for adjuvant RT' does not translate automatically to patients with glottic cancer treated by TLM. Rather, specifically patients with multiple superficial positive margins and positive deep margins after TLM need careful judging what constitutes the best additional adjuvant treatment. Second-look resection is nowadays regarded as the preferred adjuvant treatment for many of these patients whereas RT is reserved for those in whom a second look TLM is judged unlikely to result in 'true negative margins.' Additionally, when the pathology of the re-resection reveals multiple foci of residual disease or suggests again a resection with positive margins, adjuvant postoperative RT is likely to result in a better local control. If this strict selection of patients for adjuvant RT is adhered to carefully, oncological and functional results will be optimal.

Photodynamic Therapy as an Alternative Therapeutic Tool in Functionally Inoperable Oral and Oropharyngeal Carcinoma: A Single Tertiary Center Retrospective Cohort Analysis.

Background: Head and neck cancer is typically treated with surgery, radiotherapy, chemoradiation, or a combination of these treatments. This study aims to retrospectively analyse oncological outcomes, adverse events and toxicity of treatment with temoporfin-mediated photodynamic therapy at a single tertiary referral center. More specifically, in a selected group of patients with otherwise (functionally) inoperable oral or oropharyngeal head and neck squamous cell carcinoma. Methods: Twenty-six consecutive patients who received photodynamic therapy for oral or oropharyngeal squamous cell carcinoma from January 2002 until July 2019 at the University Hospitals Leuven were included. These were (1) patients with an accessible recurrent or new primary tumor in an extensively treated area of the head and neck, not suitable for standard treatment, or (2) patients that were judged medically unfit to undergo standard treatment modalities. Results: Complete tumor response immediately after PDT was obtained in 76.9% of cases. During follow-up, a proportion of CR patients did recur, to reach recurrence-free rates at six months, one year and two years of 60.6%, 48.5% and 32.3%. Local control at the PDT treated area was 42.3% with a median recurrence free interval time of 9 months. Recurrence-free interval was statistically more favorable for oropharyngeal squamous cell carcinoma (with or without oral cavity extension) in comparison to oral cavity squamous cell carcinoma alone (p < 0.001). During a median follow-up period of 27 months, we report new tumor activity in 80.8% of patients. Median overall and disease-specific survival time was 31 and 34 months, respectively. Most reported adverse events were pain after treatment and facial edema. At the end of follow-up, swallowing and upper airway functionality were preserved in 76.9 and 95.7% of patients, respectively. Conclusion: Photodynamic therapy is a valuable treatment option in highly selected patients with oral and/or oropharyngeal (functionally) inoperable head and neck squamous cell carcinoma. Treatment with this alternative modality can induce durable local control in an important fraction of treated patients, with an acceptable toxicity profile.

Oncologic Outcomes After Salvage Laryngectomy for Squamous Cell Carcinoma of the Larynx and Hypopharynx: A Multicenter Retrospective Cohort Study.

OBJECTIVE: We aimed to analyze oncologic outcomes and identify patterns of failure and negative prognostic factors in patients who underwent salvage total laryngectomy (STL) for residual, recurrent, and second primary squamous cell carcinoma (SCC) of the larynx and hypopharynx. METHODS: This was a retrospective cohort study of patients who underwent STL in four major Belgian reference hospitals between 2002 and 2018 for residual/recurrent/second primary SCC in the larynx or hypopharynx after initial (chemo)radiation. Prognostic factors for oncologic outcomes were identified using univariable and multivariable analysis. RESULTS: A total of 405 patients were included in the final analysis. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), and locoregional relapse-free survival (LRFS) estimates were 47.7% (95% confidence interval [CI] 42.0-53.2%), 68.7% (95% CI 63.7-73.7%), 42.1% (95% CI 36.7-47.4%), and 44.3% (95% CI 38.8-49.7%), respectively. In a multivariable model, increasing clinical tumor stage of the residual/recurrent/second primary tumor, increasing number of metastatic cervical lymph nodes retrieved during neck dissection, hypopharyngeal and supraglottic tumor location, positive section margin status and perineural invasion were independent negative prognostic variables for OS, DSS, DFS, and LRFS. The type of second tumor was identified as an additional independent prognosticator for DSS, with local recurrences and second primary tumors having a better prognosis than residual tumor. CONCLUSIONS AND RELEVANCE: Favorable oncologic outcomes are reported after STL. Increasing clinical tumor stage, increasing number of metastatic cervical lymph nodes, hypopharyngeal and supraglottic tumor location, positive section margins, and perineural invasion are identified as independent negative prognosticators for all oncologic outcome measures.