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Zusammenfassung. Hintergrund: Kopf-Hals-Tumore stellen Patient_innen und Angehörige wegen komplexer Behandlungen und Veränderungen vitaler Funktionen sowie des Aussehens vor große Herausforderungen. Sie benötigen vielseitige Unterstützung und profitieren von koordinierter, interprofessioneller Zusammenarbeit sowie Advanced Nursing Practice. Problem/Ziel: In einem Kopf-Hals-Tumorzentrum fehlte eine koordinierende Ansprechperson für Betroffene und das Betreuungsteam. Deshalb sollte ein Advanced Nursing Practice-Angebot entwickelt werden. Methoden: Es wurden ein Konzept für Advanced Nursing Practice, Methoden der Praxisentwicklung und Aktionsforschung eingesetzt. Das Projekt verlief in vier Phasen: Nach Stakeholderanalyse und Literaturrecherche wurde das Angebot konzipiert, in einer Pilotphase getestet und mittels Struktur-/Prozessdaten sowie einer zweiten Stakeholderbefragung evaluiert. Ergebnisse: Für Betroffene wurde eine evidenzbasierte, kontinuierliche, personenzentrierte Betreuung über das Behandlungskontinuum gefördert. Die Expertise von Pflegenden sowie die Zusammenarbeit mit internen und externen Fachpersonen wurde gefördert. Betroffene schätzten die Kontinuität, welche die Advanced Practice Nurse bot. Diskussion: Die methodischen Ansätze unterstützten ein zielorientiertes Vorgehen, insbesondere wurden durch partizipative Praxisentwicklung Befürchtungen von Mitarbeitenden aufgefangen. Grenzen/Transfer: Ein nachhaltiges Angebot kann noch nicht gewährleistet werden. Zu empfehlen ist das Vorgehen mit Stakeholderanalyse, interprofessionellem Fokus und frühzeitigem Planen der Evaluation.

Background In recent years, the list of tumor entities in the sinonasal tract has significantly expanded, requiring advanced diagnostic testing. We report the case of a 32-year-old patient with an unusual NUT carcinoma originating in the maxillary sinus, which showed extensive well-differentiated, papillary squamous morphology, similar to the spectrum of the recently described DEK::AFF2 fusion-associated carcinoma. Methods We performed immunohistochemical and molecular studies including EBV- and HPV-testing, as well as DNA/RNA next generation sequencing. Results The tumor showed predominantly exophytic papillary growth with mature squamous differentiation. An additional component harbored atypical, less differentiated basaloid tumor cells with infiltration of the adjacent stroma. Conspicuous inflammation was evident. There was no evidence of HPV DNA or EBV RNA. Next-generation sequencing revealed a NUT::NSD3 gene fusion corresponding to (“speckled-type”) immunopositivity of NUT in the tumor cells. Conclusions We describe a NUT::NSD3 gene fusion-associated NUT carcinoma of the sinonasal tract with a deceptively well-differentiated papillary growth pattern, thus expanding the morphological spectrum of this typically poorly differentiated neoplasm.

Radiotherapy (RT) along with surgery is the mainstay of treatment in head and neck squamous cell carcinoma (HNSCC). Radioresistance represents a major source of treatment failure, underlining the urgent necessity to explore and implement effective radiosensitization strategies. The MET receptor widely participates in the acquisition and maintenance of an aggressive phenotype in HNSCC and modulates the DNA damage response following ionizing radiation (IR). Here, we assessed MET expression and mutation status in primary and metastatic lesions within a cohort of patients with advanced HNSCC. Moreover, we investigated the radiosensitization potential of the MET inhibitor tepotinib in a panel of cell lines, in vitro and in vivo, as well as in ex vivo patient-derived organotypic tissue cultures (OTC). MET was highly expressed in 62.4% of primary tumors and in 53.6% of lymph node metastases (LNM), and in 6 of 9 evaluated cell lines. MET expression in primaries and LNMs was significantly associated with decreased disease control in univariate survival analyses. Tepotinib abrogated MET phosphorylation and to distinct extent MET downstream signaling. Pretreatment with tepotinib resulted in variable radiosensitization, enhanced DNA damage, cell death, and G2–M-phase arrest. Combination of tepotinib with IR led to significant radiosensitization in one of two tested in vivo models. OTCs revealed differential patterns of response toward tepotinib, irradiation, and combination of both modalities. The molecular basis of tepotinib-mediated radiosensitization was studied by a CyTOF-based single-cell mass cytometry approach, which uncovered that MET inhibition modulated PI3K activity in cells radiosensitized by tepotinib but not in the resistant ones.

Supplementary Table 1 shows HNSCC patients' characteristics

Supplementary figure 1 provides data concerning establishment of organotypic tissue cultures from freshly-resected HNSCC specimen Supplementary figure 2 shows analyses of MET expression and mutational status in a HNSCC cohort Supplementary figure 3 shows impact of MET inhibition by tepotinib in HNSCC cell lines in vitro Supplementary figure 4 shows effects of combined treatment by tepotinib and ionizing radiation on HNSCC cell lines Supplementary figure 5 shows analyses of OTCs responses to treatment by tepotinib combined with ionizing radiation Supplementary figure 6 shows results of assays studying mechanisms underlying tepotinib-mediated radiosensitization of HNSCC cell lines

Supplementary Methods

Supplementary Table 2 provides odds ratio per protein (CyTOF measurements)

Importance: Multidisciplinary perioperative assessment for patients undergoing complex oncologic head and neck cancer (HNC) surgery is widely implemented. However, to our knowledge, the association of multiprofessional preoperative assessment, information, and briefing with postoperative outcomes has not been evaluated. Objective: To compare postoperative complications, length of hospital stay (LOS), readmissions, mortality, and costs per case among patients undergoing complex oncologic HNC surgery before and after the implementation of a comprehensive preoperative multiprofessional assessment and information day (MUPAID). Design, Setting, and Participants: This retrospective, single-center case-control study was conducted at a tertiary referral head and neck anticancer center/university cancer institute and compared patients with HNC who were undergoing complex oncological surgeries between January 2012 and July 2018 before (control group) and after (intervention group) implementation of the institutional MUPAID. Data analysis was conducted between 2019 and 2020. The intervention group comprised patients who participated in the MUPAID beginning in February 2015. These patients were assessed by a multiprofessional team and provided with structured and comprehensive information on the surgical procedure and its functional, social, financial, and psychological effects, as well as the postoperative care, rehabilitation, and follow-up period. Patients in the control group had also undergone complex oncologic HNC surgery and were selected through surgical procedure codes. Main Outcomes and Measures: The end points were postoperative rate and severity of complications, LOS, readmissions, mortality, and costs per case. Results: The study included 161 patients, 81 in the intervention (25 women [30.9%]) and 80 in the control group (18 women [22.5%]). The groups showed no relevant differences in sociodemographic, disease, and procedural characteristics. The intervention cohort presented with fewer major local and systemic complications (Clavien-Dindo score, III-V: 34.6% vs 52.5%; difference proportion, −0.179; 95% CI, −0.33 to −0.03), shorter median LOS (12 days [IQR, 10-16 days] vs 16 days [IQR, 11-20] days; effect size, 0.482; 95% CI Cohen d, 0.152-0.812) and decreased median charge per case ($50 848 [IQR, $42 510-$63 479] vs $69 602 [IQR, $45 631-$96 280]; effect size, 0.534; 95% CI Cohen d, 0.22-0.85). Conclusions and Relevance: The results of this case-control study suggest that MUPAID for patients who are undergoing complex oncologic HNC surgery is associated with shortened LOS and costs per case as well as decreased complications severity. These results are promising on a patient level in the potential to minimize individual treatment burden, as well as on an institutional and health care system level in the potential significant optimization of surgical outcomes and financial aspects.

Background To assess a large patient cohort with sinonasal malignancies focusing on regional involvement, recurrence and oncological outcome. Methods Patients (n = 144) with malignant tumors of the nasal cavity and paranasal sinuses were treated at our tertiary referral center between 2008 and 2019. A chart review on patient and tumor characteristics, treatment and long-term outcome was performed. Results Most frequent histological types were squamous cell carcinoma (SCC) (n = 74), adenocarcinoma (n = 24) and mucosal melanoma (n = 18). Primary therapy was surgery in 66% of patients (n = 95) of which 65.8% (n = 66) received adjuvant radiotherapy. Twenty patients (13.8%) were initially staged as cN + and in seven cases, pN + status was histopathologically confirmed. Fifty-six of 130 patients (43.1%) had a relapse after curative intended therapy, including nine loco-regional (6.9%) and seven isolated regional recurrences (5.4%). Twelve of these 16 patients with (loco-)regional recurrence had SCC. Adenoid cystic carcinoma (87.5%) and SCC (65.3%) showed the best long-term overall survival. Conclusions Regional involvement and regional recurrence are scarce. Because of rarity and heterogeneity, evidence on therapeutic management is sparse resulting in the lack of clinical guidelines. Graphical Abstract

Background Patients diagnosed with locoregionally advanced head and neck squamous cell carcinoma (LAHNSCC) regularly undergo staging with 18F-FDG PET/CT in our center. In cases of delays in radiotherapy (RT) planning CT more than 4 weeks after initial PET/CT or clinically suspected progress, PET/CT is repeated for restaging and as an RT planning reference. Our aim was to determine the impact of second-look PET/CT on stage migration, treatment change and RT planning. Methods Consequent treatment changes were categorized as minor and major. Minor changes were defined as PET/CT-based modifications of RT plans, e.g., the addition of anatomical compartments, changes in high- and low-risk dose levels or both. Major changes included changes from curative to palliative treatment intent and alterations of interdisciplinary treatment plans, such as the addition of induction chemotherapy, switch to primary surgery, no treatment and/or the necessity of additional diagnostic work-up resulting in the postponement or cancellation of treatment. Results Thirty-two newly diagnosed LAHNSCC patients who were treated between 2014 and 2018 underwent second-look PET/CT (median interval 42.5 days). Second-look PET/CT led to locoregional and distant upstaging in 3/32 and 1/32 patients, respectively. In 1/32 patients (3%), second-look PET/CT led to a palliative approach with systemic treatment. New lymph node metastases were discovered in 16 patients, 6 of whom also showed significant progression of the primary tumor, resulting in minor changes in 16 of the remaining 31 patients (52%) who were treated curatively. Conclusion If RT treatment planning of LAHNSCC was delayed by more than 4 weeks after initial PET/CT staging or when progression was clinically suspected, a second look at 18FDG-PET/CT was performed. This led to changes in treatment planning in more than half of the cases, which is expected to directly influence oncologic outcomes.

Background: Radiotherapy is a mainstay in head and neck squamous cell carcinoma (HNSCC) treatment but is mostly applied without stratification by molecular diagnostics. Development of reliable biomarkers may have the potential to improve radiotherapy (RT) efficacy and reduce toxicity. We conducted a systematic review to summarize the field of biomarkers in HNSCC treated by RT. Methods: Pubmed and EMBASE were searched independently by two researchers following pre-defined inclusion and exclusion criteria. Z curves were generated to investigate publication bias. OncoKB was used for identification of druggable targets. Results: 134 manuscripts remained for data extraction. 12% of tumors were AJCC/UICC stage I–II and 82% were stage III–IV. The most common biomarkers were proteins (39%), DNA (14%) and mRNA (9%). Limiting analysis to prospective data and statistically significant results, we found three potentially druggable targets: ERCC2, PTCH1 and EGFR. Regarding data quality, AJCC/UICC stage was missing in 32% of manuscripts. 73% of studies were retrospective and only 7% were based on prospective randomized trials. Z-curves indicated the presence of publication bias. Conclusion: An abundance of potential biomarkers in HNSCC is available but data quality is limited by retrospective collection, lack of validation and publication bias. Improved study design and reporting quality might accelerate successful development of personalized treatments in HNSCC.

Advanced nursing practice model for head and neck cancer: A practice development project

Surgery and radiotherapy are well-established standards of care for unilateral stage 0 and I early-stage glottic cancer (ESGC). Based on comparative studies and meta-analyses, functional and oncological outcomes after both treatment modalities are similar. Historically, radiotherapy (RT) has been performed by irradiation of the whole larynx. However, only the involved vocal cord is being treated with recently introduced hypofractionated concepts that result in 8 to 10-fold smaller target volumes. Retrospective data argues for an improvement in voice quality with non-inferior local control. Based on these findings, single vocal cord irradiation (SVCI) has been implemented as a routine approach in some institutions for ESGC in recent years. However, prospective data directly comparing SVCI with surgery is lacking. The aim of VoiceS is to fill this gap.In this prospective randomized multi-center open-label phase III study with a superiority design, 34 patients with histopathologically confirmed, untreated, unilateral stage 0-I ESGC (unilateral cTis or cT1a) will be randomized to SVCI or transoral COTo our knowledge, VoiceS is the first randomized phase III trial comparing SVCI with TLM. Results of this study may lead to improved decision-making in the treatment of ESGC.ClinicalTrials.gov NCT04057209. Registered on 15 August 2019. Cantonal Ethics Committee KEK-BE 2019-01506.

Objectives Sinonasal squamous cell carcinomas are rare and aggressive tumors. Curative therapy includes surgery and radiotherapy, with high risk for local morbidity and impaired quality of life. The objective of this study was to analyze a large cohort of patients with sinonasal squamous cell carcinoma on treatment morbidity and oncological outcome. Methods Patients with sinonasal squamous cell carcinoma (n = 75) treated at a tertiary referral center between 2008 and 2019 were identified. In patients with curative treatment intent (n = 70), a chart review and analysis on patient and tumor characteristics, morbidity, and oncological outcome was performed. Results Mean follow-up was 59 months. Primary curative therapy was surgery alone (n = 18), surgery with radiation (n = 25), and primary (chemo)radiation (n = 27). Forty-two (60%) patients suffered from treatment-related morbidity; most frequent symptoms were dry nasal mucosa (20%), nasal obstruction (14.3%), and vision impairment or loss (11.5%). Patients with early disease had less morbidity (51.4 vs 71.1%; P = 0.09), a lower recurrence rate (27% vs. 48.5%; P = 0.08), and better overall survival (92.5% vs. 71.1%; P = 0.01). Conclusion Treatment-related morbidity is common after curative treatment of sinonasal squamous cell carcinomas. Early disease is beneficial in terms of occurrence and severity as multimodal treatment and recurrence can more likely be avoided.

Major congenital anomalies are known to play a role in the management and prognosis of airway obstruction. Most studies assess acquired forms of airway obstruction. Data on congenital or otherwise non-acquired forms of airway obstruction is sparse. In this retrospective, single-institution cohort study, we sought to evaluate and compare the patterns of airway obstruction in children with and without major congenital anomalies, and to assess the impact of management and outcome, irrespective of aetiology. Fifty-five patients were included, 23 with and 32 without underlying major congenital anomalies. Multilevel airway obstruction (usually affecting the nasopharynx, oropharynx, and the trachea) was more common in children with congenital anomalies (91% vs. 41%, p < .001). Consequently, these children required more frequent and earlier surgical management, especially tracheostomy and adenotonsillar surgery.Conclusions: Major congenital anomalies are associated with multilevel airway obstruction and poor functional prognosis. A simple clinical definition considering impact of major congenital anomalies on development and growth may help guide management plans following endoscopic evaluation of the entire airway and flanked by multidisciplinary discussions. What is Known:• Children with major comorbidities display increased disease severity and more prevalent multilevel airway obstruction• Previous studies include both children with acquired and non-acquired forms of airway obstruction; therefore, the actual impact major comorbidities in children with non-acquired causes of airway obstruction remain unclear. What is New:• A total of 42% children in this study population had major comorbidities with and impact on growth and/or psychomotor development, with a higher prevalence of multilevel airway obstruction and worse rates of functional improvement/recovery.• Children with major comorbidities require tracheostomy more often and earlier than those without major comorbidities, and remain tracheostomy-dependent for a longer time.

Aim The potential impact of the daytime and season of radiotherapy application on acute and late toxicity burden was analyzed on a cohort of curatively treated head and neck squamous cell carcinoma patients. Methods Through a retrospective chart review, patient and tumor characteristics, treatment parameters and outcome were obtained. Patients treated with definitive or adjuvant radiotherapy with and without chemotherapy receiving ≥60 Gy between 2002 and 2015 were included (n = 617). Daily fraction times and dates were extracted. Median radiotherapy delivery time of each patient was categorized as morning (AM) and afternoon (PM). Treatment season was defined by the median day of the treatment course. Each year was divided into DARK and LIGHT by the March and September equinoxes. Acute (T) and late (A) toxicity were defined by TAME methodology. Results Median follow-up was 51 months. Mean T and A scores during and after radiotherapy in DARK vs. LIGHT were 1.98 vs. 1.61 (p = 0.0127) and 0.41 vs. 0.30 (p = 0.1699), respectively. Mean T and A scores during and after AM vs. PM radiotherapy were 1.71 vs. 1.88 (p = 0.0387) and 0.31 vs. 0.41 (p = 0.2638), respectively. Multivariate analyses indicated DARK vs. LIGHT as the only independent treatment time-related factor among other factors such as tumor subsite, UICC stage, radiotherapy technique, and chemotherapy for T. Conclusion This is the first study investigating the impact of seasonality on toxicity burden, showing higher acute toxicity with radiotherapy in DARK. The daytime did not predict the toxicity. The hypothesis-generating findings of this retrospective study should be further investigated.

OBJECTIVE Fear of recurrence (FoR) affects the quality of life of head and neck cancer survivors. Identification of factors predisposing to FoR may help to recognize and treat patients at risk. MATERIALS AND METHODS For this exploratory study, 101 disease-free head and neck cancer survivors completed a cross-sectional survey in 2017 that included the FoR questionnaire at a random point in time during their follow-up. Additionally, the patients were asked to choose their favorite among four follow-up schedules with or without systematic imaging and varying frequency of visits. RESULTS Elevated FoR was present in 36.6% of patients. Females and patients ≤65 years showed significantly higher FoR overall scores than males (score difference 3.40; CI 0.49-6.32; p = 0.022) and patients >65 years (score difference 4.25; CI 1.58-6.92; p = 0.002). A history of cancer recurrence or second primary malignancy increased the relative risk (RR) for elevated FoR (RR 1.7; CI 1.01-2.86; p = 0.046). Tumor stage and treatment modality were not significantly associated with elevated FoR or FoR overall score. Higher FoR overall scores were recorded in patients who favored intensive follow-up plans (mean overall FoR score 18 vs. 15; SD 7.7; p = 0.076) and systematic imaging in follow-up (17 vs. 13, SD 7.1; p = 0.034). CONCLUSION Fear of recurrence in head and neck cancer patients is associated with female sex, younger age, and history of a past recurrence or second primary malignancy. Due to its high prevalence, it should be addressed in clinical practice and future research. LEVEL OF EVIDENCE N/A Laryngoscope, 2022.

Aim: Lymph node (LN) metastases are associated with poor outcomes in patients with recurrent larynx squamous cell carcinoma (LSCC). Neck dissection (ND) is therefore commonly performed along with salvage total laryngectomy (STL). Here, we assess the rate of occult LN metastases and the diagnostic value of MRI and PET/CT for detecting them in recurrent LSCC. Methods: This retrospective study included patients with recurrent LSCC after primary (chemo)radiotherapy [(C)RT] who were re-staged by MRI and/or PET/CT and treated with STL and ND between 2004 and 2019. The histopathology of ND samples was used as the reference standard. Results: Forty-one patients were included. The prevalence of occult metastases in MRI-negative and PET/CT-negative neck nodes was between 3.2% and 6.1%. Negative predictive values of neck node re-staging were 93.9% for MRI, 96.8% for PET/CT, and 96.2% for MRI and PET/CT combined. Conclusion: Both MRI and PET/CT afforded good negative predictive values for nodal staging in patients with recurrent LSCC after (C)RT prior to STL. In selected patients, these radiological modalities, particularly PET/CT, could help to avoid unnecessary surgery to the neck and its associated morbidity.

Postoperative complications in head and neck surgery are well-known, but a predictive model to guide clinicians in free flap reconstructions has not been established. This retrospective single-center observational study assessed 131 patients who underwent ablative surgery and received free flap reconstruction. Primary endpoint was the occurrence of systemic complications (PSC). Secondary endpoint was the generation of a nomogram of complications according to the CDC classification. In the ordinal regression model, postoperative administration of furosemide [1.36 (0.63–2.11), p < 0.0001], blood loss [0.001 (0.0004–0.0020), p = 0.004], postoperative nadir hemoglobin [−0.03 (−0.07–0.01), p = 0.108], smoking [0.72 (0.02–1.44), p = 0.043], and type of flap reconstruction [1.01 (0.21–1.84), p = 0.014] as predictors. A nomogram with acceptable discrimination was proposed (Somer's delta: 0.52). Application of this nomogram in clinical practice could help identify potentially modifiable risk factors and thus reduce the incidence of postoperative complications in patients undergoing microvascular reconstruction of the head and neck.

Objectives The aim of this study was to determine the influence of perioperative fluid management and administration of vasopressors on early surgical revision and flap-related complications in free tissue transfer. Materials and methods Intraoperative amount of fluid and of vasopressors, relevant perioperative parameters, and comorbidities were recorded in 131 patients undergoing head and neck microvascular reconstruction and compared with early surgical complications, defined as interventions requiring surgery after a flap-related complication, and/or other surgical problems in the operating room within 30 days after initial surgery. The relationship between perioperative variables for each revision category was determined using an optimized multiple logistic regression. Results The administration of diuretics (p=0.001) as a treatment for perioperative fluid overload and the type of flap (p=0.019) was associated with a higher risk of early surgical revisions. Perioperative fluid overload (p=0.039) is significantly related to flap-related complications. We found no effect of intraoperative administration of vasopressors on early surgical revisions (p=0.8) or on flap-related complications (norepinephrine p=0.6, dobutamine p=0.5). Conclusion Perioperative fluid overload is associated with higher risks of early surgical revision and flap-related complications. In contrast, the administration of vasopressors seemed to have no effect on either surgical revision rate or flap-related complications. Clinical relevance In patients receiving microvascular reconstructions, a balanced fluid administration perioperatively and a targeted use of vasopressors should be the necessary strategy to reduce the complication rates in head and neck surgery.

Background: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human cancers, with a median survival of only three to six months. Standard treatment options and even targeted therapies have so far failed to improve long-term overall survival. Thus, novel treatment modalities for ATC, such as immunotherapy, are urgently needed. CD47 is a "don't eat me" signal, which prevents cancer cells from phagocytosis by binding to signal regulatory protein alpha on macrophages. So far, the role of macrophages and the CD47-signal regulatory protein alpha signaling axis in ATC is not well understood. Methods: This study analyzed 19 primary human ATCs for macrophage markers, CD47 expression, and immune checkpoints by immunohistochemistry. ATC cell lines and a fresh ATC sample were assessed by flow cytometry for CD47 expression and macrophage infiltration, respectively. CD47 was blocked in phagocytosis assays of co-cultured macrophages and ATC cell lines. Anti-CD47 antibody treatment was administered to ATC cell line xenotransplanted immunocompromised mice, as well as to tamoxifen-induced ATC double-transgenic mice. Results: Human ATC samples were heavily infiltrated by CD68- and CD163-expressing tumor-associated macrophages (TAMs), and expressed CD47 and calreticulin, the dominant pro-phagocytic molecule. In addition, ATC tissues expressed the immune checkpoint molecules programmed cell death 1 and programmed death ligand 1. Blocking CD47 promoted the phagocytosis of ATC cell lines by macrophages in vitro. Anti-CD47 antibody treatment of ATC xenotransplanted mice increased the frequency of TAMs, enhanced the expression of macrophage activation markers, augmented tumor cell phagocytosis, and suppressed tumor growth. In double-transgenic ATC mice, CD47 was expressed on tumor cells, and blocking CD47 increased TAM frequencies. Conclusions: Targeting CD47 or CD47 in combination with programmed cell death 1 may potentially improve the outcomes of ATC patients and may represent a valuable addition to the current standard of care.

Metastases and tumor recurrence have a major prognostic impact in head and neck squamous cell carcinoma (HNSCC); however, cellular models that comprehensively characterize metastatic and recurrent HNSCC are lacking. To this end, we obtained genomic, transcriptomic, and copy number profiles of the UM-SCC cell line panel, encompassing patient-matched metastatic and recurrent cells. UM-SCC cells recapitulate the most prevalent genomic alterations described in HNSCC, featuring common TP53, PI3K, NOTCH, and Hippo pathway mutations. This analysis identified a novel F977Y kinase domain PIK3CA mutation exclusively present in a recurrent cell line (UM-SCC14B), potentially conferring resistance to PI3K inhibitors. Small proline-rich protein 2A (SPRR2A), a protein involved in epithelial homeostasis and invasion, was one of the most consistently downregulated transcripts in metastatic and recurrent UM-SCC cells. Assessment of SPRR2A protein expression in a clinical cohort of patients with HNSCC confirmed common SPRR2A downregulation in primary tumors (61.9% of cases) and lymph node metastases (31.3%), but not in normal tissue. High expression of SPRR2A in lymph node metastases was, along with nonoropharyngeal location of the primary tumor, an independent prognostic factor for regional disease recurrence after surgery and radiotherapy (HR 2.81; 95% CI, 1.16–6.79; P = 0.02). These results suggest that SPRR2A plays a dual role in invasion and therapeutic resistance in HNSCC, respectively through its downregulation and overexpression. Implications: The current study reveals translationally relevant mechanisms underlying metastasis and recurrence in HNSCC and represents an adjuvant tool for preclinical research in this disease setting. Underlining its discovery potential this approach identified a PIK3CA-resistant mutation as well as SPRR2A as possible theragnostic markers.

The diagnostic role of fine-needle aspiration cytology (FNAC) and core-needle biopsy (CNB) has not been comprehensively assessed in head and neck sarcomas. A systematic review of published cases (1990-2020) was conducted. Diagnostic performance of both FNAC/CNB to determine tumor dignity and histopathological diagnosis was calculated. One hundred and sixty-eight cases were included for which FNAC (n = 156), CNB (n = 8), or both (n = 4) were used. Predominant histologies were skeletal muscle, chondrogenic and vascular sarcomas. FNAC correctly assessed dignity in 76.3% and histology in 45% of cases. Dignity was significantly better for vascular tumors, metastatic and recurrent specimens, and worse for chondrogenic sarcomas. CNB showed a 92% accuracy to identify dignity and 83% for histopathology. FNAC and CNB are useful methods for the diagnosis of head and neck sarcomas, particularly well-suited in the context of recurrent or metastatic disease. The role of CNB remains largely unexplored for this indication.

Highlights • The potential value of a second look PET/CT prior to radiotherapy was investigated. • New lymph node metastases were discovered in half of the patients. • Progression of the primary tumor and distant metastases were also observed. • This strategy led to changes in treatment planning in more than half of the cases., Background Patients diagnosed with locoregionally advanced head and neck squamous cell carcinoma (LAHNSCC) regularly undergo staging with 18F-FDG PET/CT in our center. In cases of delays in radiotherapy (RT) planning CT more than 4 weeks after initial PET/CT or clinically suspected progress, PET/CT is repeated for restaging and as an RT planning reference. Our aim was to determine the impact of second-look PET/CT on stage migration, treatment change and RT planning. Methods Consequent treatment changes were categorized as minor and major. Minor changes were defined as PET/CT-based modifications of RT plans, e.g., the addition of anatomical compartments, changes in high- and low-risk dose levels or both. Major changes included changes from curative to palliative treatment intent and alterations of interdisciplinary treatment plans, such as the addition of induction chemotherapy, switch to primary surgery, no treatment and/or the necessity of additional diagnostic work-up resulting in the postponement or cancellation of treatment. Results Thirty-two newly diagnosed LAHNSCC patients who were treated between 2014 and 2018 underwent second-look PET/CT (median interval 42.5 days). Second-look PET/CT led to locoregional and distant upstaging in 3/32 and 1/32 patients, respectively. In 1/32 patients (3%), second-look PET/CT led to a palliative approach with systemic treatment. New lymph node metastases were discovered in 16 patients, 6 of whom also showed significant progression of the primary tumor, resulting in minor changes in 16 of the remaining 31 patients (52%) who were treated curatively. Conclusion If RT treatment planning of LAHNSCC was delayed by more than 4 weeks after initial PET/CT staging or when progression was clinically suspected, a second look at 18FDG-PET/CT was performed. This led to changes in treatment planning in more than half of the cases, which is expected to directly influence oncologic outcomes.

Purpose Parapharyngeal space neoplasms (PSNs) are rare tumors of the head and neck region. In this study, we report our institutional experience with PSNs over a 27-years period. Methods Patients treated between 1992 and 2018 were identified through our tumor board database. Data concerning demographics, clinical presentation, disease features, treatment, complications and follow-up were obtained retrospectively. Results In total, 48 patients were identified. Most patients had benign tumors (67.5%), with pleomorphic adenoma and schwannoma being the most frequent entities. Malignant tumors represented the remaining 32.5% of neoplasms. Concerning tissue of origin, 67.5% of neoplasms originated from salivary glands and 17.5% were neurogenic. The vast majority of PSNs required open surgical approaches (77%). The most frequent reversible and irreversible complications included paralysis of facial, vagal, and hypoglossal nerves (transient 62.5%, permanent 31.3%). Tumor recurrences occurred in 16.7% of our patients. Conclusion Neoplasms of the parapharyngeal space (PPS) are rare. In our series, consistent with the literature, most patients had benign tumors. Fine-needle aspiration cytology (FNAC) and/or transoral biopsy in selected cases combined with radiographic imaging are helpful to plan the optimal approach (open/transoral) and extent of primary surgery. Close follow-up in malignant neoplasms is crucial to assess recurrence early. We present one of the largest recent studies on PPS tumors treated in a center. Given the low incidence of these tumors, our results contribute to the existing sparse evidence regarding the management and outcome of such tumors.

The aim of this study was to determine the influence of perioperative fluid management and administration of vasopressors on early surgical revision and flap-related complications in free tissue transfer.Intraoperative amount of fluid and of vasopressors, relevant perioperative parameters, and comorbidities were recorded in 131 patients undergoing head and neck microvascular reconstruction and compared with early surgical complications, defined as interventions requiring surgery after a flap-related complication, and/or other surgical problems in the operating room within 30 days after initial surgery. The relationship between perioperative variables for each revision category was determined using an optimized multiple logistic regression.The administration of diuretics (p=0.001) as a treatment for perioperative fluid overload and the type of flap (p=0.019) was associated with a higher risk of early surgical revisions. Perioperative fluid overload (p=0.039) is significantly related to flap-related complications. We found no effect of intraoperative administration of vasopressors on early surgical revisions (p=0.8) or on flap-related complications (norepinephrine p=0.6, dobutamine p=0.5).Perioperative fluid overload is associated with higher risks of early surgical revision and flap-related complications. In contrast, the administration of vasopressors seemed to have no effect on either surgical revision rate or flap-related complications.In patients receiving microvascular reconstructions, a balanced fluid administration perioperatively and a targeted use of vasopressors should be the necessary strategy to reduce the complication rates in head and neck surgery.

Background The potential impact of daytime and season of radiotherapy application on prognosis is unclear. This was analyzed in a retrospective cohort of patients who were diagnosed with non-metastatic head and neck squamous cell carcinoma (HNSCC) and treated with definitive radiotherapy with or without chemotherapy. Materials and methods Patient and tumor characteristics, treatment parameters and outcome until last follow-up or death were obtained. Median radiotherapy delivery daytime of each patient was categorized as morning (AM) and afternoon (PM). Treatment season was defined by median date of treatment course. Each year was divided into DARK and LIGHT according to equinoxes. Time-to-event endpoints were defined by first biopsy confirming the HNSCC. Results Six hundred fifty-five cases were identified who were treated with (chemo)radiotherapy between 2002 and 2015. Median follow-up was 47 months. No significant heterogeneity in patient, tumor and treatment characteristics were observed between DARK and LIGHT or regarding median daily fraction time (X2 p > 0.05). Five-year loco-regional control (73% vs. 61%; p = 0.0108) and progression-free survival (51% vs. 43%; p = 0.0374) were superior when radiotherapy was administered in DARK. Neither the daytime nor any other treatment time-related parameter affected prognosis. Conclusion This is the first study investigating and presenting the prognostic impact of seasonality regarding the treatment course on loco-regional control and progression-free survival (DARK > LIGHT). The biological mechanism of action is unclear. These results should be interpreted with caution and our findings have to be validated externally.

CASE REPORT We report on the case of a 47-year old woman with granulocyte colony-stimulating factor (G-CSF)-producing relapsed oropharyngeal squamous cell cancer. Palliative immunotherapy with nivolumab was started. Absolute neutrophilic count increased during the course of immunotherapy and correlated with tumour progression. Under chemotherapy with weekly paclitaxel, dramatic tumour regression and decreasing absolute neutrophilic count were noted. G-CSF concentration in serum increased from 4.77 to 9.61 pg/ml during the final phase of tumour progression. Immunohistochemical staining of the initial biopsies showed that some of the tumour cells as well as infiltrating cells stained positively for G-CSF, and some of the tumour cells even stained positively for the G-CSF receptor. CONCLUSION Leukaemoid reaction in malignant disease with increased neutrophilic granulocytes has been shown to correlate with dismal prognosis in other tumours. The role of G-CSF in progression and prognosis of head and neck squamous cell carcinomas is still unclear but in patients with these tumours there seems also to be a correlation between elevated G-CSF and poor prognosis. Further systematic evaluation of G-CSF secretion in this tumour entity should clarify the role and potential treatment possibilities for these tumours.

OBJECTIVES/HYPOTHESIS Hypopharyngeal squamous cell carcinoma (SCC) is a rare but aggressive malignancy, with low survival rates and high incidence of tumor and treatment-related morbidity. This study aims to analyze the long-term oncologic and functional outcomes of a large cohort of patients and to determine prognostic factors. STUDY DESIGN Retrospective cohort study. METHODS The records of all patients diagnosed with hypopharyngeal SCC and treated with curative intent at our tertiary referral center were reviewed. Patient and initial disease characteristics, features, and complications of primary treatment, recurrence patterns, and corresponding treatments and the oncologic and functional long-term outcome were determined. RESULTS For a total of 179 patients, primary radiotherapy (RT) was the predominant treatment modality (78%), whereas 22% underwent primary surgery. The median, 2-year, and 5-year overall survival (OS) for the study cohort were 47 months, 64% and 43%. The median survival after first and second relapse was 7 and 6 months, respectively. The 2 and 5-year relapse-free survival (RFS) was 52% and 36%. The median RFS after first relapse and salvage treatment was 9 months. A nodal status of ≥cN2 (HR = 1.89, CI:1.21-3.05, P

OBJECTIVES/HYPOTHESIS To assess the ability of specific positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) features to detect extracapsular extension (ECE) in head and neck squamous cell carcinoma (HNSCC) patients. STUDY DESIGN Retrospective study in a tertiary certified university cancer institute. METHODS We performed a review of patients with advanced HNSCC at Bern University Hospital between 2014 and 2018. Patients with pretherapeutic PET/CT and/or MRI who underwent neck dissection were included, with 212 patients fulfilling inclusion criteria. Blinded evaluation of specific PET/CT and MRI features with respect to presence of ECE was performed. Histopathological examination of neck dissection specimens was used as the gold standard to determine ECE status. RESULTS Out of the 212 included patients, 184 had PET/CT, 186 MRI, and 158 both modalities. Overall clinical stage IV (odds ratio [OR]: 2.26, 95% confidence interval [CI]: 2.25-11.74), ill-defined margins in both PET/CT and MRI (OR: 3.48, 95% CI: 1.21-9.98 and OR: 2.14, 95% CI: 0.94-4.89, respectively), and a maximum standardized uptake value ≥ 10 (OR: 5.44, 95% CI: 1.21-9.98) were all significant independent predictors of ECE. When combined, these four features led to a cumulative score able to predict ECE status with an accuracy of 91.43%. CONCLUSIONS The current findings indicate specific features in PET/CT and MRI are potential predictors of ECE status and may help in pretherapeutic stratification in HNSCC. LEVEL OF EVIDENCE 4 Laryngoscope, 2020.

For the treatment of early and locally advanced glottic laryngeal cancer, multiple strategies are available. These are pursued and supported by different levels of evidence, but also by national and institutional traditions. The purpose of this review article is to compare and discuss the current evidence supporting different loco-regional treatment approaches in early and locally advanced glottic laryngeal cancer. The focus is kept on randomized controlled trials, meta-analyses, and comparative retrospective studies including the treatment period within the last twenty years (≥ 1999) with at least one reported five-year oncologic and/or functional outcome measure. Based on the equipoise in oncologic and functional outcome after transoral laser surgery and radiotherapy, informed and shared decision-making with and not just about the patient poses a paramount importance for T1-2N0M0 glottic laryngeal cancer. For T3-4aN0-3M0 glottic laryngeal cancer, there is an equipoise regarding the partial/total laryngectomy and non-surgical modalities for T3 glottic laryngeal cancer. Patients with extensive and/or poorly functioning T4a laryngeal cancer should not be offered organ-preserving chemoradiotherapy with salvage surgery as a back-up plan, but total laryngectomy and adjuvant (chemo) radiation. The lack of high-level evidence comparing contemporary open or transoral robotic organ-preserving surgical and non-surgical modalities does not allow any concrete conclusions in terms of oncological and functional outcome. Unnecessary tri-modality treatments should be avoided. Instead of offering one-size-fits-all approaches and over-standardized rigid institutional strategies, patient-centered informed and shared decision-making should be favored.

Salivary duct carcinoma (SDCa) is a rare cancer with high rate of metastases and poor survival despite aggressive multimodality treatment. This study analyzes the genetic changes in SDCa, their impact on cancer pathways, and evaluates whether molecular patterns can identify subgroups with distinct clinical characteristics and outcome. Clinicopathologic details and tissue samples from 66 patients (48 males, 18 females) treated between 1995 and 2018 were obtained from multiple institutions. Androgen receptor (AR) was assessed by immunohistochemistry, and the Illumina TruSight 170 gene panel was used for DNA sequencing. Male gender, lympho-vascular invasion, lymph node metastasis, and smoking were significant predictors of disease-free survival. AR was present in 79%. Frequently encountered alterations were mutations in TP53 (51%), PIK3CA (32%) and HRAS (22%), as well as amplifications of CDK4/6 (22%), ERBB2 (21%), MYC (16%), and deletions of CDKN2A (13%). TP53 mutation and MYC amplifications were associated with decreased disease-free survival. Analysis of cancer pathways revealed that the PI3K pathway was most commonly affected. Alterations in the cell cycle pathway were associated with impaired disease-free survival (HR 2.6, P = 0.038). Three subgroups based on AR and ERBB2 status were identified, which featured distinct molecular patterns and outcome. Among AR positive SDCa, HRAS mutations were restricted to AR positive tumors without ERBB2 amplification and HRAS mutations featured high co-occurrence with PIK3CA alterations, which seems specific to SDCa. AR negative SDCa were associated with poor disease-free survival in multivariate analysis (HR 4.5, P = 0.010) and none of these tumors exhibited ERBB2 amplification or HRAS mutations. AR and ERBB2 status in SDCa thus classifies tumors with distinct molecular profiles relevant to future targeted therapy. Furthermore, clinical factors such as smoking and molecular features such as MYC amplification may serve as markers of poor prognosis of SDCa.

Background Current studies about percutaneous endoscopic gastrostomy (PEG) tube placement report equivalent patient outcomes with prophylactic PEG tubes (pPEGs) versus common nutritional support. Unreported was if omitting a pPEG is associated with an increased risk of complications leading to a treatment-related unplanned hospitalization (TRUH). Methods TRUHs were retrospectively analyzed in patients with advanced head and neck squamous cell carcinoma (n = 310) undergoing (chemo)radiotherapy with (pPEG) or without PEG (nPEG). Results In 88 patients (28%), TRUH was reported. One of the leading causes of TRUH in nPEG patients was inadequate oral intake (n = 16, 13%), and in pPEG patients, complications after PEG tube insertion (n = 12, 10%). Risk factors for TRUH were poor performance status, tobacco use, and surgical procedures. Conclusions Omitting pPEG tube placement without increasing the risk of an unplanned hospitalization due to dysphagia, dehydration or malnutrition, is an option in patients being carefully monitored. Patients aged > 60 years with hypopharyngeal carcinoma, tobacco consumption, and poor performance status appear at risk of PEG tube-related complications leading to an unplanned hospitalization.

OBJECTIVES Parotid lymph node metastases are common in head and neck cutaneous squamous cell carcinoma (cSCCHN). Here we evaluate the diagnostic, prognostic, and therapeutic implications of intraglandular lymph node (IGLN) metastases in cSCCHN. STUDY DESIGN Retrospective study in a tertiary referral university cancer institute. METHODS We included patients with cSCCHN who underwent parotidectomy and neck dissection (ND), with or without synchronous resection of the skin primary, between January 1999 and January 2018. The characteristics of cSCCHN with or without IGLN involvement were compared. RESULTS Altogether, 68 patients were included. Of the 29 (42.6%) patients classified as cN0, eight were upstaged pN+ and had concomitant IGLN involvement. Of 21 patients with pN0 disease, IGLN metastases were absent in only three cases, resulting in a specificity and sensitivity of parotid metastases to diagnose occult nodal neck metastases of 14.29% and 100%, respectively. The positive and negative predictive values were 14.29% and 100%, respectively. Univariate analyses only displayed a significantly higher rate of moderately and poorly differentiated primaries in patients with IGLN metastases (P = .015). Only advanced T-stages were significantly associated with neck recurrences. CONCLUSION IGLN status in advanced cSCCHN is potentially predictive for occul nodal neck metastases. Our results suggest that ND in patients with histopathologically negative IGLNs and clinically negative neck lymph nodes may not be necessary given the high negative predictive value of IGLN status in this group of patients. Therefore, accurate diagnostic evaluation of IGLN involvement is mandatory. LEVEL OF EVIDENCE 4 Laryngoscope, 2020.

Management of the neck lymph nodes is an integral part in the therapeutic approach of head and neck cancer. Within this context, neck dissection entails the removal of nodal levels contained in the cervical soft and fat tissue. Extent of surgery depends on several factors, including the site and stage of primary tumor and clinically metastatic involvement of neck lymph nodes. Levels at risk are systematically removed while preserving or when indicated selectively resecting the muscular, vascular and nervous structures of the neck. In this chapter, we discuss the surgical approach to the neck lymph nodes in the frame of head and neck cancer treatment and we review the main complications of neck dissection.

Ceruminous pleomorphic adenoma is a very rare, mostly benign tumor originating from the ceruminal glands in the external auditory canal. Histologically, it is a mixed tumor with epithelial and stromal parts of different proportions, and is recognized today by the World Health Organization (WHO) as a ceruminous adenoma. Similar to the pleomorphic adenoma of salivary glands, recurrence or malignant degeneration with cellular atypia and metastasis can occur on rare occasions. Here, we describe an 87-year old female patient with a growing spherical mass in the right external auditory canal. After exclusive endoscopic tumor resection, a ceruminous pleomorphic adenoma was histologically diagnosed. Due to the absence of nuclear pleomorphism, no increased mitotic rate, no perineural invasion and no fusion transcripts of the MYB or MYBL1 gene loci, an adenoid cystic carcinoma could be excluded. The postoperative course was without any evidence of complications. A literature review identified 44 articles with 49 patients that were considered. Hearing loss and ear sensations were the most commonly reported symptoms. Most cases underwent an excision via an endaural or retroauricular approach. Recurrences were described in four patients, three of which had a malignant transformation. Keywords: Pleomorphic adenoma; ceruminal gland tumor; ceruminous adenoma; endoscopic ear surgery; external auditory canal.

The neck affords one of the most surgically complex anatomy in the human body, as it contains vital or otherwise functionally relevant structures. Among these are the upper aero-digestive tract, the great neck vessels and cranial nerves VII, X, XI and XII along with the cervical and brachial plexus, and the phrenic nerve. Accurate knowledge of this intricate anatomy is essential to avoid complications, particularly long-term functional impairment, mainly following injury of nervous structures. The neck harbors more than 300 lymph nodes, whose physiopathological role in conditions such as infections and cancer represent an important surgically therapeutic target. In this chapter, we review the cervical fasciae and lymphatic drainage patterns of the neck as basis for its international known lymph node level system I–VI. Furthermore, the nodal levels are delineated in-depth while emphasizing the most important anatomical landmarks.

BACKGROUND Patients with head and neck squamous cell carcinoma (HNSCC) often acquire an impaired nutritional status resulting in compromised outcomes. Perioperative immunonutrition may have a positive effect on outcomes after elective surgery. METHODS Short-term outcomes before and after implementation of preoperative immunonutrition were retrospectively assessed. Regression models adjusted for outcome predictors were used to compare the length of stay (LOS) in the hospital, local infections, and general complications. RESULTS Four hundred eleven patients were included (control group = 209 and the intervention group = 202). With immunonutrition, hospital LOS was significantly lower (median 6 vs 8 days; adjusted mean difference of -5.65 days; P

Key Clinical Message Obstructive sleep apnea syndrome (OSAS) is a widespread and underdiagnosed disease. Causes are mostly related to obesity and anatomy with oro‐pharyngeal narrowing. Parapharyngeal tumors are rare but can easily be treated. Careful oro‐pharyngeal examination in OSAS patient is cheap, easy to perform by non‐ENT specialists, quick, and avoids inadequate treatment.

BACKGROUND The optimal treatment strategy for stage I-II glottic squamous cell carcinoma (SCC) is not well-defined. This study analyzed treatment results and prognostic factors. PATIENTS AND METHODS This is a single-institution retrospective analysis of 244 patients with T1-2 glottic SCC who underwent normofractionated radiotherapy (RT) and/or surgery between 1990 and 2013. The primary endpoint was relapse-free survival (RFS). RESULTS Median age was 65 years (range: 36-92 years), the majority (82%) having stage I disease. Definitive RT was used in 82% (median dose: 68 Gy, 2 Gy per fraction). Median follow-up was 59 months. The 5‑year RFS rates were 83 and 75% (p = 0.05) for stage I and 62 and 50% (p = 0.47) for stage II in the RT and surgery groups, respectively. Multivariate analyses indicate T1 vs. T2 and RT vs. surgery as independent prognostic factors for RFS, with hazard ratios of 0.38 (95% confidence interval, CI: 0.21-0.72) and 0.53 (95% CI: 0.30-0.99), respectively (p < 0.05). The 5‑year overall and cause-specific survival rates in the whole cohort were 92 and 96%, respectively, with no significant differences between treatment groups. Anterior commissure involvement was neither a prognostic nor a predictive factor. The incidence of secondary malignancies was not significantly different between patients treated with and without RT (22 vs. 9% at 10 years, respectively, p = 0.18). CONCLUSION Despite a possible selection bias, our series demonstrates improved RFS with RT over surgery in stage I glottic SCC.

Tam S et al. Estimating Survival After Salvage Surgery for Recurrent Oral Cavity Cancer. JAMA Otolaryngol Head Neck Surg 2017; 143:685–690 Loko-regionäre Rezidive eines Plattenepithelkarzinoms der Mundhöhle sind lebensbedrohlich und eine klinische Herausforderung. Welche Rolle spielt in diesen Fällen die Salvage-Chirurgie?

OBJECTIVES/HYPOTHESIS Head and neck squamous cell carcinoma (HNSCC) has a high tendency for regional lymphatic spreading. Nevertheless, isolated regional lymph node recurrences are rare, and only limited data regarding its management are available. The aim of this study was to describe treatment modalities and outcomes, and to identify prognostic factors. Study Design Retrospective cohort study. METHODS The records of all patients (n = 498) with tumor persistence or recurrence after curatively intended treatment for HNSCC were retrospectively reviewed. Patients with synchronous secondary tumors at initial presentation, tumor persistence, local or locoregional recurrence, and systemic metastases were excluded. RESULTS A total of 76 patients were included. The rate of occult additional metastasis in radiologically uninvolved neck compartments during salvage neck dissection was 25%. The salvaged patients showed a 37.5% 5-year recurrence-free survival (RFS). Multivariate analysis revealed initial stage IVA-B (hazard ratio [HR]: 4.16, P

Background: The Head and Neck Cancer Working Group of Swiss Group for Clinical Cancer Research (SAKK) has investigated the level of consensus (LOC) and discrepancy in everyday practice of diagnosis and treatment in head and neck cancer. Materials and Methods: An online survey was iteratively generated with 10 Swiss university and teaching hospitals. LOC below 50% was defined as no agreement, while higher LOC were arbitrarily categorized as low (51-74%), moderate (75-84%), and high (≥85%). Results: Any LOC was achieved in 62% of topics (n = 60). High, moderate, and low LOC were found in 18, 20, and 23%, respectively. Regarding Head and Neck Surgery, Radiation Oncology, Medical Oncology, and biomarkers, LOC was achieved in 50, 57, 83, and 43%, respectively. Conclusions: Consensus on clinical topics is rather low for surgeons and radiation oncologists. The questions discussed might highlight discrepancies, stimulate standardization of practice, and prioritize topics for future clinical research.

Background: The Head and Neck Cancer Working Group of Swiss Group for Clinical Cancer Research (SAKK) has investigated the level of consensus (LOC) and discrepancy in everyday practice of diagnosis and treatment in head and neck cancer. Materials and Methods: An online survey was iteratively generated with 10 Swiss university and teaching hospitals. LOC below 50% was defined as no agreement, while higher LOC were arbitrarily categorized as low (51-74%), moderate (75-84%), and high (≥85%). Results: Any LOC was achieved in 62% of topics (n = 60). High, moderate and low LOC were found in 18, 20, and 23%, respectively. Regarding Head and Neck Surgery, Radiation Oncology, Medical Oncology, and biomarkers, LOC was achieved in 50, 57, 83, and 43%, respectively. Conclusions: Consensus on clinical topics is rather low for surgeons and radiation oncologists. The questions discussed might highlight discrepancies, stimulate standardization of practice, and prioritize topics for future clinical research.

Dysphagia represents one of the most serious adverse events after curative-intent treatments with a tremendous impact on quality of life in patients with head and neck cancers. Novel surgical and radiation therapy techniques have been developed to better preserve swallowing function, while not negatively influencing local control and/or overall survival. This review focuses on the current literature of swallowing outcomes after curative treatment strategies. Available results from recent studies relevant to this topic are presented, demonstrating the potential role of new treatment modalities for early- and intermediate-stage oropharyngeal cancers. Based on this, we present the rationale and design of the currently active EORTC 1420 "Best of" trial, and highlight the potential of this study to help prioritizing either surgery- or radiation-based treatment modalities for the treatment of oropharyngeal cancer in the future. ispartof: FRONTIERS IN ONCOLOGY vol:9 ispartof: location:Switzerland status: published