Case-tailored indicated extracapsular dissection versus "one-size-fits-all" nerve dissection: Has the bet been won?

OBJECTIVE: The aim of the study was to trace the development of surgical therapy in a large cohort, examine its changes at one single institution that has been specializing in salivary gland pathologies over the last 22 years, and to determine the extent to which a possible shift in the surgical therapy of parotid benign tumors towards less radical methods was correlated with a change in the incidence of facial palsy and Frey's syndrome. STUDY DESIGN: Retrospective clinical study. METHODS: A retrospective evaluation of the records of all patients treated for benign parotid tumors at a tertiary referral center between 2000 and 2022 was carried out. Surgical methods were classified into four groups: extracapsular dissection, partial superficial parotidectomy, superficial parotidectomy and complete parotidectomy. RESULTS: A total of 4037 patients were included in the study. Our analysis demonstrated an increase in the total number of parotidectomies for benign lesions from 71 (2000) to 298 (2022), mostly due to the increase in extracapsular dissections (from 9 to 212). The increased performance of less radical surgery was associated with a significantly decreased incidence of perioperative complications. CONCLUSIONS: Our study showed that the increased performance of less radical surgery was associated with better functional outcomes over the years.

Postoperative Pain Following Eye Enucleation: A Prospective Observational Study.

Background and Objectives: Enucleation of an eye is the most invasive procedure in ophthalmologic surgery. It can be the result of various diseases (malignant/chronic/trauma/infection) and is nevertheless relatively rare, but leads to the loss of a strongly innervated neuronal organ. This study systematically evaluates postoperative pain levels following enucleation of the eye globe. Materials and Methods: This prospective single-center study enrolled twenty-four patients undergoing enucleation of the eye globe. Perioperatively all patients completed (preoperative day, day of surgery, 1st, 2nd, and 3rd day following surgery) standardized questionnaires concerning their pain experience and treatment-related side-effects (internal protocol, QUIPS, painDETECT®). Patients received usual pain therapy in an unstandardized individual manner. Results: Preoperatively, mean average pain intensity of all included patients was 3.29 ± 2.46 (range, 0-8), 3.29 ± 3.24 (range, 0-8) on the day of surgery, 4.67 ± 1.90 (range, 2-10) on day 1, 3.25 ± 1.39 (range, 1-6) on day 2, and 2.71 ± 1.30 (range, 1-6) on day 3 after surgery. Mean maximum pain intensity was 4.71 ± 3.28 (range, 0-10) preoperatively, 4.04 ± 3.78 (range, 0-10) on the day of surgery, 5.75 ± 2.01 (range, 2-10) on day 1, 4.25 ± 1.89 (range, 2-10) on day 2, and 3.88 ± 1.54 (range, 2-8) on day 3 after surgery. Nineteen patients (79.2%) stated that they would have preferred more pain therapy. Conclusions: Patients undergoing eye enucleation report pain sensations in need of intervention in this university hospital. Thus, effective standardized pain treatment concepts are now a high priority to be established in an interdisciplinary manner containing standardized regimens and continuous regional procedures. Awareness of this problem in the medical team should be sharpened through targeted training and information.

Machine Learning-assisted immunophenotyping of peripheral blood identifies innate immune cells as best predictor of response to induction chemo-immunotherapy in head and neck squamous cell carcinoma - knowledge obtained from the CheckRad-CD8 trial.

PURPOSE: Individual prediction of treatment response is crucial for personalized treatment in multimodal approaches against head-and-neck squamous cell carcinoma (HNSCC). So far, no reliable predictive parameters for treatment schemes containing immunotherapy have been identified. This study aims to predict treatment response to induction chemo-immunotherapy based on the peripheral blood immune status in patients with locally advanced HNSCC. METHODS: The peripheral blood immune phenotype was assessed in whole blood samples in patients treated in the phase II CheckRad-CD8 trial as part of the pre-planned translational research program. Blood samples were analyzed by multicolor flow cytometry before (T1) and after (T2) induction chemo-immunotherapy with cisplatin/docetaxel/durvalumab/tremelimumab. Machine Learning techniques were used to predict pathological complete response (pCR) after induction therapy. RESULTS: The tested classifier methods (LDA, SVM, LR, RF, DT, and XGBoost) allowed a distinct prediction of pCR. Highest accuracy was achieved with a low number of features represented as principal components. Immune parameters obtained from the absolute difference (lT2-T1l) allowed the best prediction of pCR. In general, less than 30 parameters and at most 10 principal components were needed for highly accurate predictions. Across several datasets, cells of the innate immune system such as polymorphonuclear cells, monocytes, and plasmacytoid dendritic cells are most prominent. CONCLUSIONS: Our analyses imply that alterations of the innate immune cell distribution in the peripheral blood following induction chemo-immuno-therapy is highly predictive for pCR in HNSCC.

The modified Polsby-Popper score, a novel quantitative histomorphological biomarker and its potential to predict lymph node positivity and cancer-specific survival in oral tongue squamous cell carcinoma.

BACKGROUND: The significance of different histological spreading patterns of tumor tissue in oral tongue squamous cell carcinoma (TSCC) is well known. Our aim was to construct a numeric parameter on a continuous scale, that is, the modified Polsby-Popper (MPP) score, to describe the aggressiveness of tumor growth and infiltration, with the potential to analyze hematoxylin and eosin-stained whole slide images (WSIs) in an automated manner. We investigated the application of the MPP score in predicting survival and cervical lymph node metastases as well as in determining patients at risk in the context of different surgical margin scenarios. METHODS: We developed a semiautomated image analysis pipeline to detect areas belonging to the tumor tissue compartment. Perimeter and area measurements of all detected tissue regions were derived, and a specific mathematical formula was applied to reflect the perimeter/area ratio in a comparable, observer-independent manner across digitized WSIs. We demonstrated the plausibility of the MPP score by correlating it with well-established clinicopathologic parameters. We then performed survival analysis to assess the relevance of the MPP score, with an emphasis on different surgical margin scenarios. Machine learning models were developed to assess the relevance of the MPP score in predicting survival and occult cervical nodal metastases. RESULTS: The MPP score was associated with unfavorable tumor growth and infiltration patterns, the presence of lymph node metastases, the extracapsular spread of tumor cells, and higher tumor thickness. Higher MPP scores were associated with worse overall survival (OS) and tongue carcinoma-specific survival (TCSS), both when assessing all pT-categories and pT1-pT2 categories only; moreover, higher MPP scores were associated with a significantly worse TCSS in cases where a cancer-free surgical margin of <5 mm could be achieved on the main surgical specimen. This discriminatory capacity remained constant when examining pT1-pT2 categories only. Importantly, the MPP score could successfully define cases at risk in terms of metastatic disease in pT1-pT2 cancer where tumor thickness failed to exhibit a significant predictive value. Machine learning (ML) models incorporating the MPP score could predict the 5-year TCSS efficiently. Furthermore, we demonstrated that machine learning models that predict occult cervical lymph node involvement can benefit from including the MPP score. CONCLUSIONS: We introduced an objective, quantifiable, and observer-independent parameter, the MPP score, representing the aggressiveness of tumor growth and infiltration in TSCC. We showed its prognostic relevance especially in pT1-pT2 category TSCC, and its possible use in ML models predicting TCSS and occult lymph node metastases.

Explainable convolutional neural networks for assessing head and neck cancer histopathology.

PURPOSE: Although neural networks have shown remarkable performance in medical image analysis, their translation into clinical practice remains difficult due to their lack of interpretability. An emerging field that addresses this problem is Explainable AI. METHODS: Here, we aimed to investigate the ability of Convolutional Neural Networks (CNNs) to classify head and neck cancer histopathology. To this end, we manually annotated 101 histopathological slides of locally advanced head and neck squamous cell carcinoma. We trained a CNN to classify tumor and non-tumor tissue, and another CNN to semantically segment four classes - tumor, non-tumor, non-specified tissue, and background. We applied Explainable AI techniques, namely Grad-CAM and HR-CAM, to both networks and explored important features that contributed to their decisions. RESULTS: The classification network achieved an accuracy of 89.9% on previously unseen data. Our segmentation network achieved a class-averaged Intersection over Union score of 0.690, and 0.782 for tumor tissue in particular. Explainable AI methods demonstrated that both networks rely on features agreeing with the pathologist's expert opinion. CONCLUSION: Our work suggests that CNNs can predict head and neck cancer with high accuracy. Especially if accompanied by visual explanations, CNNs seem promising for assisting pathologists in the assessment of cancer sections.

Radiotherapy combined with docetaxel alters the immune phenotype of HNSCC cells and results in increased surface expression of CD137 and release of HMGB1 of specifically HPV-positive tumor cells.

PURPOSE: Human papilloma virus (HPV) positive head and neck squamous cell carcinoma (HNSCC) tumors respond significantly better to anticancer treatments. It is assumed to be due to a better response to radiotherapy (RT), and presumably to an increased immunogenicity. However, little is known how the immune phenotype of HNSCC tumor cells is modulated by standard treatment, namely by radiochemotherapy (RCT). METHODS: Therefore, we aimed to examine the impact of the HPV status on the immune phenotype of HNSCC cell lines following RCT with 5 × 3Gy or 1 × 19.3Gy and/or docetaxel, by analyzing cell death, release of damage-associated molecular patterns (DAMPs), surface expression of immune checkpoint molecules (ICMs) and the impact on activation of human monocyte-derived dendritic cells (hmDCs). RESULTS: Cell death induction and Hsp70 release following RCT was independent of the HPV status, and RCT significantly increased the expression of the immune suppressive ICMs PD-L1, PD-L2 and HVEM. An immune stimulatory ICM, CD137, was significantly increased following RCT only on HPV-positive cell lines, as well as the release of HMGB1. Although the treatment increased cell death and modulated ICM expression in HNSCC, the hmDCs were not activated after co-incubation with treated tumor cells. CONCLUSION: Our data with the HPV-dependent release of HMGB1 and increased expression of CD137 following RCT provide a hint for increased immunogenicity underlining the better prognosis for HPV positive tumors following RCT.

A comparison between p16-positive head and neck cancer of unknown primary (HPV-HNCUP) and oropharyngeal squamous cell carcinoma (HPV-OPSCC): are they the same disease?

INTRODUCTION: The following study aimed to answer the question if HPV-HNCUP and HPV-OPSCC are the same disease. Propensity score matching (PSM) was used to compare the oncological outcomes of both groups, in particular the 5-year overall survival rate (OS), the 5-year disease specific survival rate (DSS) and the 5-year progression free survival rate (PFS). MATERIALS AND METHODS: Firstly, between January 1st, 2007, and March 31st, 2020 a total of 131 patients were treated with HNCUP at our Department. Out of these, 21 patients with a confirmed positive p16 status were referred to surgery followed by adjuvant therapy. Secondly, between January 1st, 2000, and January 31st, 2017, a total of 1596 patients were treated with an OPSSC at our Department. Out of these, 126 patients with a confirmed positive p16 status were referred to surgery followed by adjuvant therapy. After PSM, 84 patients with HPV-OPSCC and 21 HPV-HNCUP remained in the study for further comparison. RESULTS: The OS was 63.5% (95% CI 39.4-87.6) for HPV-HNCUP and 88.9% (95% CI 90.4-100.0) for HPV-OPSCC patients and therefore, significantly lower for the first mentioned (p = 0.013). The DSS was also significantly impaired for HPV-HNCUP (71.0%, 95% CI 46.3-95.7), in comparison with HPV-OPSCC patients (95.5%, 95% CI 90.4-100.0; p = 0.002). The PFS for HPV-HNCUP patients was lower (75.6%, 95% CI 54.0-97.2) yet not significantly different to HPV-OPSCC (90.4%, 95% CI 83.5-97.3; p = 0.067). CONCLUSIONS: The results presented demonstrate a significant reduced OS and DSS for HPV-HNCUP patients. Accordingly, in our study HPV-HNCUP and HPV-OPSCC are two different entities with a different oncological outcome.

[Highlights of the ASCO and ESMO annual meetings 2022: radiotherapy of head and neck cancer]. / Highlights der ASCO- und ESMO­Jahrestagungen 2022: Strahlentherapie von Kopf­Hals­Tumoren.

At the 2022 annual meetings of the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO), several studies on radiation therapy for head and neck squamous cell carcinoma (HNSCC) were presented. Among the main topics were new concepts for treatment de-escalation with the goal of reducing side effects. Radiotherapy alone for nasopharyngeal carcinoma with an intermediate-risk profile was found to be noninferior to chemoradiotherapy with cisplatin while improving tolerability. In the phase II DIREKHT trial for adjuvant radiotherapy, individualized deintensification concepts of radiation dose or volume were implemented. Overall, this treatment resulted in excellent levels of locoregional control with a minimal side effects profile. In subgroup analysis, however, an increased locoregional recurrence rate was observed for tumors of the oral cavity. In 2022, as in the previous year, there was a continued focus on the role of immune checkpoint inhibitors in combination with platinum-based chemoradiotherapy in the first-line treatment of locally advanced HNSCC. In the HNSCC-15-132 trial, sequential application of the PD­1 inhibitor pembrolizumab to chemoradiotherapy was not significantly, but numerically superior to concomitant application. The phase III KEYNOTE-412 trial evaluated the efficacy of concomitant and sequential additive pembrolizumab therapy compared to additive placebo in 804 patients with locally advanced HNSCC. The observed benefit in terms of event-free survival in the pembrolizumab group marginally missed statistical significance, probably due to the particular study design. In addition, new 5­year overall survival data from the phase II trial of chemoradiotherapy in combination with the inhibitor of apoptosis proteins (IAP) antagonist xevinapant versus placebo were presented. The xevinapant group continued to demonstrate a significant survival advantage and a sustained response to treatment.

Risk of magnetic resonance imaging-induced magnet dislocation for different types of cochlear implants: a single-center retrospective study.

BACKGROUND: When performing magnetic resonance imaging (MRI) in patients with a cochlear implant (CI), complication rates vary widely in the literature. The primary objective of this retrospective study was to determine the prevalence of complications, in particular magnet dislocation, in patients with CI undergoing 1.5 Tesla (T) MRI. As a secondary objective, the prevalence of magnet dislocation for specific cochlear implant device types was elaborated. METHODS: In a single-center retrospective study, all patients with a cochlear implant presenting for an MRI examination at 1.5 T at our institution between January 1st, 2010 and December 31st, 2020 were included. Implants with axial and diametrical magnets were included in the study. MRI safety measures were applied before imaging. The prevalence of complications was evaluated. Magnet dislocation rates were calculated for device types with at least 20 MRI exposures. RESULTS: During the study period, 196 MRI examinations were performed in a total of 128 patients, accounting for 149 different implants (21 implanted bilaterally) with a total of 231 implant exposures to MRI (average 1.69 ± 1.57; min. 1, max. 12). Complications were reported in 50 out of 231 cochlear implant exposures (21.6%). Magnet dislocation occurred in a total of 27 cases (11.7%). Dislocation rates were 29.6% for the Cochlear® CI500 series (24 dislocations from 81 exposures), 1.1% for the Cochlear® CI24RE series (1 from 87) and 0% for the MED-EL® Synchrony (0 from 36). The dislocation rate for the CI500 was significantly higher than for the CI24RE (χ2(1) = 26.86; p < 0.001; ϕ = 0.40) or the Synchrony (χ2(1) = 13.42; p < 0.001; ϕ = 0.34). CONCLUSIONS: For 1.5 T MRI, the risk of magnet dislocation ranges from 0 to 29.6% and depends on the CI device type. Implants with a diametrical magnet can be considered potentially MRI-safe, whereas in CIs with axial magnets, the CI500 is at high risk of magnet dislocation. Therefore, apart from a strict indication for an MRI and adherence to safety protocols, post-MRI follow-up examination to rule out magnet dislocation is recommended.

Deep learning for automatic head and neck lymph node level delineation provides expert-level accuracy.

Background: Deep learning-based head and neck lymph node level (HN_LNL) autodelineation is of high relevance to radiotherapy research and clinical treatment planning but still underinvestigated in academic literature. In particular, there is no publicly available open-source solution for large-scale autosegmentation of HN_LNL in the research setting. Methods: An expert-delineated cohort of 35 planning CTs was used for training of an nnU-net 3D-fullres/2D-ensemble model for autosegmentation of 20 different HN_LNL. A second cohort acquired at the same institution later in time served as the test set (n = 20). In a completely blinded evaluation, 3 clinical experts rated the quality of deep learning autosegmentations in a head-to-head comparison with expert-created contours. For a subgroup of 10 cases, intraobserver variability was compared to the average deep learning autosegmentation accuracy on the original and recontoured set of expert segmentations. A postprocessing step to adjust craniocaudal boundaries of level autosegmentations to the CT slice plane was introduced and the effect of autocontour consistency with CT slice plane orientation on geometric accuracy and expert rating was investigated. Results: Blinded expert ratings for deep learning segmentations and expert-created contours were not significantly different. Deep learning segmentations with slice plane adjustment were rated numerically higher (mean, 81.0 vs. 79.6, p = 0.185) and deep learning segmentations without slice plane adjustment were rated numerically lower (77.2 vs. 79.6, p = 0.167) than manually drawn contours. In a head-to-head comparison, deep learning segmentations with CT slice plane adjustment were rated significantly better than deep learning contours without slice plane adjustment (81.0 vs. 77.2, p = 0.004). Geometric accuracy of deep learning segmentations was not different from intraobserver variability (mean Dice per level, 0.76 vs. 0.77, p = 0.307). Clinical significance of contour consistency with CT slice plane orientation was not represented by geometric accuracy metrics (volumetric Dice, 0.78 vs. 0.78, p = 0.703). Conclusions: We show that a nnU-net 3D-fullres/2D-ensemble model can be used for highly accurate autodelineation of HN_LNL using only a limited training dataset that is ideally suited for large-scale standardized autodelineation of HN_LNL in the research setting. Geometric accuracy metrics are only an imperfect surrogate for blinded expert rating.

Differences in Need for Opioids After Sinonasal Surgery at Day of Surgery and in the Postoperative Period.

INTRODUCTION: In the last years, the use of opioid analgesics has increased, as well as their morbidity and mortality, especially in the United States. Most patients after sinonasal surgery receive opioid analgesics, although up to 90% have leftover opioid pills. Around 70% of these patients keep the opioid analgesics, which could possibly lead to improper use. The objective of the following study was the investigation of the need for, use of, timing and side effects of opioid and non-opioid analgesics after sinonasal surgery. METHODS: This was a retrospective study of (n = 280) patients who underwent sinonasal surgery in the Otolaryngology Department of the University Erlangen-Nürnberg between January and December 2018. The postoperative pain (3-5 days after surgery) using the numeric rating scale and the postoperative need for on-demand opioids and non-opioid analgesics in relation to demographic and surgical parameters were evaluated. RESULTS: Of total, 59.64% of all patients received opioid analgesics postoperatively on the day of surgery. On the first postoperative day (POD1), the mean pain score yielded the highest values; however, only 0.71% of the patients needed opioid analgesics, and pain was sufficiently controlled with non-opioids or no pain medication at all. There was a significant reduction of the pain score from POD2 to 5 (P = .01; P < .01, respectively). Only 1.8% of the patients needed an opioid analgesic from POD1-5. Of total, 2.1% of the patients presented with a postoperative bleeding complication, and only 1 (0.4%) patient needed endoscopic coagulation. CONCLUSION: Our results indicate that the majority of patients need opioid analgesics almost exclusively on the day of surgery. There were no major complications in patients taking either opioid or non-opioids. Our results indicate that the postoperative pain regimen from POD1 should initially be started using non-opioid analgesics and be further escalated to opioid analgesics in individual cases.

Limited parotid surgery as sole form of treatment for carefully selected malignant tumours of the parotid gland: Still sufficient on the long-term?

BACKGROUND: The aim of the study was to investigate the oncological and functional outcome following extracapsular dissection as the sole form of treatment in locally limited low-grade malignant parotid tumours in the long term. METHODS: The records of all patients treated for T1-T2 low-grade malignant tumours of the parotid gland solely by means of extracapsular dissection between 2005 and 2017 were studied retrospectively. RESULTS: A total of 16 cases formed our study sample (7 men, 9 women). Their mean age was 50.2 years (21-84 years). Mean follow-up was 107 months (60-201 months). In 6 cases the tumour was an acinic cell carcinoma, in 9 cases a mucoepidermoid carcinoma and in one case a basal cell adenocarcinoma. Regarding the T category, the tumour was Tis in one case, T1 in 12 cases and T2 in three cases. The five-year disease-specific survival rate was 100 %, as was local disease control. Facial nerve function was House-Brackmann grade I without exception. CONCLUSIONS: Our study showed very encouraging long-term results following primary extracapsular dissection as the sole surgical therapy for carefully selected low-stage, low-grade, inferiorly located lesions in patients with high compliance. LAY SUMMARY: The "one-size-fits-all" strategy of complete parotidectomy with neck dissection might be tantamount to overtreatment by less aggressive cases of parotid cancer. Extracapsular dissection seems to be oncologically sufficient for carefully selected T1-T2 low-grade cases in the long-term in patients with ensured follow-up.

Analgesia after tonsillectomy with controlled intravenous morphine - overdue or exaggerated?

Abstract Objective: To assess the value of a morphine Patient Controlled Intravenous Analgesia (PCIA) after Tonsillectomies (TE). Methods: 30 adult patients were treated with oral analgesics (protocol group) and compared to 30 patients treated with a morphine PCIA for the first 3 Postoperative Days (PODs) after TE. Average and maximum pain severities (Numeric Rating Scale - NRS: 0-10) on PODs 1-3, analgesic score, quality of life, patient satisfaction and side effects were defined as outcome measures. Results: Average pain severities of the protocol and the PCIA group were of similar magnitude (NRS) (POD1: 4.48 vs. 4.71 [p = 0.68], POD2: 4.75 vs. 4.22 [p = 0.32] and POD3: 4.44 vs. 4.25 [p = 0.71]). Maximum pain intensities on POD1 (p = 0.92), POD2 (p = 0.51) and POD3 (p = 0.36) were also comparable between both groups. Patients with a PCIA consumed significantly more opioids (p = 0.001) without significant more side-effects. Conclusion: The PCIA did not provide a superior pain control compared to oral analgesics. In view of the considerable effort and the high opioid consumption, it cannot be recommended as a standardized application for pain control after TE.

Additional Diffusion-Weighted Imaging with Background Body Signal Suppression (DWIBS) Improves Pre-Therapeutical Detection of Early-Stage (pT1a) Glottic Cancer: A Feasibility and Interobserver Reliability Study.

(1) Background: Early-stage glottic cancer is easily missed on magnetic resonance imaging (MRI). Diffusion-weighted imaging (DWI) may improve diagnostic accuracy. Therefore, our aim was to assess the value of adding diffusion-weighted imaging with background body signal suppression (DWIBS) to pre-therapeutic MRI staging. (2) Methods: Two radiologists with 8 and 13 years of experience, blinded to each other's findings, initially interpreted only standard MRI, later DWIBS alone, and afterward, standard MRI + DWIBS in 41 patients with histopathologically proven pT1a laryngeal cancer of the glottis. (3) Results: Detectability rates with standard MRI, DWIBS only, and standard MRI + DWIBS were 68-71%, 63-66%, and 73-76%, respectively. Moreover, interobserver reliability was calculated as good (κ = 0.712), very good (κ = 0.84), and good (κ = 0.69) for standard MRI, DWIBS only, and standard MRI + DWIBS, respectively. (4) Conclusions: Standard MRI, DWIBS alone, and standard MRI + DWIBS showed an encouraging detection rate, as well as distinct interobserver reliability in the diagnosis of early-stage laryngeal cancer when compared to the definitive histopathologic report.

Case report: Patient specific combination of surgery and immunotherapy in advanced squamous cell carcinoma of the head and neck - a case series and review of literature.

Background: Prognosis of patients with recurrent or metastatic head and neck cancer is generally poor. Adjuvant immunotherapy (IT) featuring immune checkpoint inhibition (ICI) is standard of care in advanced stage head and neck squamous cell carcinoma (HNSCC) and cutaneous squamous cell carcinoma (CSCC). ICI response rates in CSCC are described as higher than in HNSCC. IT is constantly shifting into earlier disease stages which confronts the surgeon with immunotherapeutically pre-treated patients. It is therefore becoming increasingly difficult to assess which patients with symptomatic tumor disease and a lack of curative surgical option might benefit from salvage surgery. Case presentations: The following 6 cases describe therapeutic decision-making regarding ICI and (salvage) surgery in patients with advanced stage HNSCC or CSCC. Cases A and B focus on neoadjuvant ICI followed by salvage surgery. In Cases C and D salvage surgery was performed after short-term stabilization with partial response to ICI. The last two cases (Cases E and F) address the surgical approach after failure of ICI. All cases are discussed in the context of the current study landscape and with focus on individual decision-making. For better understanding, a timetable of the clinical course is given for each case. Conclusions: ICI is rapidly expanding its frontiers into the neoadjuvant setting, frequently confronting the surgeon with heavily pretreated patients. Salvage surgery is a viable therapeutic concept despite the rise of systemic treatment options. Decision-making on surgical intervention in case of a salvage surgery remains an individual choice. For neoadjuvant ICI monitoring regarding pathological tumor response or tumor necrosis rate, we suggest correlation between the initial biopsy and the definite tumor resectate in order to increase its significance as a surrogate marker. Scheduling of neoadjuvant ICI should be further investigated, as recent studies indicate better outcomes with shorter time frames.

Differences and Similarities in the Pattern of Early Metabolic and Morphologic Response after Induction Chemo-Immunotherapy versus Induction Chemotherapy Alone in Locally Advanced Squamous Cell Head and Neck Cancer.

Background: In head and neck cancer patients, parameters of metabolic and morphologic response of the tumor to single-cycle induction chemotherapy (IC) with docetaxel, cis- or carboplatin are used to decide the further course of treatment. This study investigated the effect of adding a double immune checkpoint blockade (DICB) of tremelimumab and durvalumab to IC on imaging parameters and their significance with regard to tumor cell remission. Methods: Response variables of 53 patients treated with IC+DICB (ICIT) were compared with those of 104 who received IC alone. Three weeks after one cycle, pathologic and, in some cases, clinical and endoscopic primary tumor responses were evaluated and correlated with a change in 18F-FDG PET and CT/MRI-based maximum-standardized uptake values (SUVmax) before (SUVmaxpre), after treatment (SUVmaxpost) and residually (resSUVmax in % of SUVmaxpre), and in maximum tumor diameter (Dmax) before (Dmaxpre) and after treatment (Dmaxpost) and residually (resD). Results: Reduction of SUVmax and Dmax occurred in both groups; values were SUVmaxpre: 14.4, SUVmaxpost: 6.6, Dmaxpre: 30 mm and Dmaxpost: 23 mm for ICIT versus SUVmaxpre: 16.5, SUVmaxpost: 6.4, Dmaxpre: 21 mm, and Dmaxpost: 16 mm for IC alone (all p < 0.05). ResSUVmax was the best predictor of complete response (IC: AUC: 0.77; ICIT: AUC: 0.76). Metabolic responders with resSUVmax ≤ 40% tended to have a higher rate of CR to ICIT (88%; n = 15/17) than to IC (65%; n = 30/46; p = 0.11). Of the metabolic nonresponders (resSUVmax > 80%), 33% (n = 5/15) achieved a clinical CR to ICIT versus 6% (n = 1/15) to IC (p = 0.01). Conclusions: ICIT and IC quickly induce a response and 18F-FDG PET is the more accurate modality for identifying complete remission. The rate of discrepant response, i.e., pCR with metabolic nonresponse after ICIT was >30%.

Systematic classification of confocal laser endomicroscopy for the diagnosis of oral cavity carcinoma.

INTRODUCTION: Confocal laser endomicroscopy (CLE) is an optical imaging technique that allows in vivo microscope-like images of the upper aerodigestive tract's mucosa in 1000-fold magnification. The assessment of morphological tissue characteristics for the correct differentiation between healthy and malignoma suspected mucosa requires strict evaluation criteria. This study aims to validate a score for oral cavity squamous cell carcinoma (OCSCC) diagnostic. METHODS: We performed CLE and examined a total of twelve patients. All 95 sequences (778 s, 6224 images) originate from the area of the primary tumor 260 s, 2080 images) and unsuspicious mucosa of the oral cavity (518 s, 4144 images). Specimen were taken at corresponding locations and analyzed histologically in H&E staining as a reference standard. A total of eight examiners (four experienced and four inexperienced) evaluated the sequences based on a scoring system. The primary endpoints are sensitivity, specificity, and accuracy. Secondary endpoints are inter-rater reliability and receiver operator characteristics. RESULTS: Healthy mucosa showed epithelium with uniform size and shape with distinct cytoplasmic membranes and regular vessel architecture. CLE of malignant cells demonstrated a disorganized arrangement of variable cellular morphology. We calculated an accuracy, sensitivity, specificity, PPV, and NPV of 88.7 %, 90.1 %, 87.4 %, 87.5 %, and 90.0 %, respectively, with inter-rater reliability and κ-value of 0.775, and an area under the curve of 0.935. CONCLUSIONS: The results confirm that this scoring system is applicable in the oral cavity mucosa to classify benign and malignant tissue.

Factors Influencing the Outcome of Head and Neck Cancer of Unknown Primary (HNCUP).

Background: This study on patients with head and neck cancer of unknown primary (HNCUP) assesses the impact of surgical and non-surgical treatment modalities and the tumour biology on the oncological outcome. Methods: A total of 80 patients with HNCUP (UICC I−IV) were treated with simultaneous neck dissection followed by adjuvant therapy, between 1 January 2007 and 31 March 2020. As the primary objective, the influence of treatment modalities on the overall survival (OS), the disease-specific survival (DSS) and the progression-free survival (PFS) were analysed in terms of cox regression and recursive partitioning. The tumour biology served as secondary objectives. Results: The 5-year OS for the entire cohort was 67.7%, (95% CI: 54.2−81.2%), the 5-year DSS was 82.3% (72.1−92.5%) and the 5-year PFS was 72.8% (61.8−83.8%). Cox regression revealed that patients undergoing adjuvant radiotherapy only had a four times higher risk to die compared to patients receiving chemoradiation therapy (HR = 4.45 (1.40; 14.17), p = 0.012). The development of distant metastases had a significantly negative impact on OS (HR = 8.24 (3.21−21.15), p < 0.001) and DSS (HR = 23.79 (6.32−89.56), p < 0.001). Recursive portioning underlined the negative influence of distant metastases on OS (3.2-fold increase in death probability) and DSS (4.3-fold increase in death probability), while an UICC stage of IVb increased the risk for further progression of the disease by a factor of 2. Conclusions: The presence of distant metastases as well as adjuvant treatment with radiation without concomitant chemotherapy, were among others, significant predictors for the overall survival of HNCUP patients, with distant metastases being the most significant predictor.

Cartilaginous bending spring tympanoplasty: a temporal bone study and first clinical results.

OBJECTIVE: Anchoring grafts for tympanic membrane (TM) reconstruction in anterior and subtotal TM defects is essential to prevent medialisation and can be facilitated by cartilaginous bending spring tympanoplasty (CBST). The purpose of this study was to analyse the impact of spring cartilages on middle ear transfer functions and patient hearing levels. METHODS: In six fresh-frozen human temporal bones a cartilage graft (measuring 6 × 2 mm with a thickness of 0.1-0.2 mm) was formed into a 'U'-shaped bending spring, to be placed between the medial tympanic wall and the tympanic underlay grafts. The stapes velocity for excitation by exponential sweeps from 400 to 10,000 Hz was measured with a laser Doppler vibrometer. The resulting middle ear transfer functions were compared with the reconstructed middle ear. For clinical evaluation, 23 ears in 21 patients with chronic otitis media and an intact ossicular chain were operated using CBST. At each follow-up visit, the patients underwent pure-tone audiometry and the Freiburg monosyllabic speech test at a presentation level of 65 dB SPL for the word recognition score (WRS). RESULTS: The measured stapes velocities at one-third octave midband frequencies averaged 3.56 × 10-2 ± 9.46 × 10-3 (mm/s/Pa) compared to 3.06 × 10-2 ± 6.86 × 10-3 (mm/s/Pa) with the bending and underlay cartilage in place (p = 0.319; r = 0.32). The bending spring tympanoplasty reduced the transfer function by 1.41 ± 0.98 dB on average. In the clinical part of the study, the graft success rate was 96% (22 out of 23 patients) after a mean follow-up of 5.8 ± 2.4 months (min. 3.5 months, max. 12.0 months). The air-bone gap improved significantly by 6.2 dB (± 6.6 dB; p < 0.001; r = 0.69), as well as the WRS from 61.8 ± 33.3% preoperatively to 80.0 ± 20.9% postoperatively (p = 0.031; r = 0.35). CONCLUSION: Experimental data as well as initial clinical results suggest that CBST is an effective method for reconstructing anterior or subtotal defects of the tympanic membrane with satisfactory audiologic results and graft success rates comparable to previously described methods. It can, therefore, be added to the arsenal of tympanoplasty techniques for anterior and subtotal TM perforations.

Advance directives in patients with head and neck cancer - status quo and factors influencing their creation.

BACKGROUND: Advance Care Planning including living wills and durable powers of attorney for healthcare is a highly relevant topic aiming to increase patient autonomy and reduce medical overtreatment. Data from patients with head and neck cancer (HNC) are not currently available. The main objective of this study was to survey the frequency of advance directives (AD) in patients with head and neck cancer. METHODS: In this single center cross-sectional study, we evaluated patients during their regular follow-up consultations at Germany's largest tertiary referral center for head and neck cancer, regarding the frequency, characteristics, and influencing factors for the creation of advance directives using a questionnaire tailored to our cohort. The advance directives included living wills, durable powers of attorney for healthcare, and combined directives. RESULTS: Four hundred and forty-six patients were surveyed from 07/01/2019 to 12/31/2019 (response rate = 68.9%). The mean age was 62.4 years (SD 11.9), 26.9% were women (n = 120). 46.4% of patients (n = 207) reported having authored at least one advance directive. These documents included 16 durable powers of attorney for healthcare (3.6%), 75 living wills (16.8%), and 116 combined directives (26.0%). In multivariate regression analysis, older age (OR ≤ 0.396, 95% CI 0.181-0.868; p = 0.021), regular medication (OR = 1.896, 95% CI 1.029-3.494; p = 0.040), and the marital status ("married": OR = 2.574, 95% CI 1.142-5.802; p = 0.023; and "permanent partnership": OR = 6.900, 95% CI 1.312-36.295; p = 0.023) emerged as significant factors increasing the likelihood of having an advance directive. In contrast, the stage of disease, the therapeutic regimen, the ECOG status, and the time from initial diagnosis did not correlate with the presence of any type of advance directive. Ninety-one patients (44%) with advance directives created their documents before the initial diagnoses of head and neck cancer. Most patients who decide to draw up an advance directive make the decision themselves or are motivated to do so by their immediate environment. Only 7% of patients (n = 16) actively made a conscious decision not create an advance directive. CONCLUSION: Less than half of head and neck cancer patients had created an advance directive, and very few patients have made a conscious decision not to do so. Older and comorbid patients who were married or in a permanent partnership had a higher likelihood of having an appropriate document. Advance directives are an essential component in enhancing patient autonomy and allow patients to be treated according to their wishes even when they are unable to consent. Therefore, maximum efforts are advocated to increase the prevalence of advance directives, especially in head and neck cancer patients, whose disease often takes a crisis-like course.