Tumor volume as a predictive parameter in the sequential therapy (induction chemotherapy) of head and neck squamous cell carcinomas.

PURPOSE: Tumor volume in locally advanced head and neck squamous cell carcinomas (LAHNSCC) treated by induction chemotherapy (ICT) and followed by radiochemotherapy (RCT) was measured. The presence of potential correlation of initial tumor volume and volume reduction after ICT and RCT with remission status, overall survival (OS) and disease-free survival (DFS) were investigated. Furthermore, reliability of approximation of the tumor volume relying on its diameter to manual three-dimensional measurement was assessed. METHODS: Data of patients with LAHNSCC treated by ICT consisting of docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by definite RCT were retrospectively analyzed. The tumor volume was calculated slice-by-slice in contrast-enhanced CT or MRI before and after ICT as well as after complete treatment. The volume was compared to radiologic remission status, correlated with OS and DFS, and to volume estimation using tumor diameter. RESULT: 65 patients were included. Primary tumor volume did not correlate with complete remission rate (CR) after ICT and RCT, OS or DFS. The change in tumor volume between baseline imaging and post-RCT had a significant impact on OS (p = 0.026) and DFS (p = 0.028). The agreement between tumor volume and radiologic remission was 72.14%. CONCLUSION: The initial tumor volume had no influence on CR, OS or DFS. A severe response to ICT did not predict a powerful RCT outcome. The change in tumor volume post-RCT had an impact on OS and DFS. Tumor volume estimation using its diameter seems to be a reliable method.

[Treatment of head and neck squamous cell carcinoma recurrences and distant metastases : Highlights of the 2018 ASCO meeting]. / Therapie der rezidivierten und fernmetastasierten Plattenepithelkarzinome des Kopf-Hals-Bereichs : Highlights des ASCO-Meetings 2018.

This year, the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC) was mainly dominated by immunotherapy. The corresponding studies are presented in another article. Beside this, results of phase II studies in particular were presented at the ASCO Annual Meeting, in which-as in recent years-new drugs (monoclonal antibodies, small molecules) played a major role. Furthermore, a clinical scoring system for prognosis evaluation in R/M-HNSCC patients was presented and the influence of HPV status on survival in this patient cohort was investigated. The studies presented herein reflect the different drug-based treatment concepts in R/M-HNSCC and represent the variety of therapeutic approaches in the recurrent and metastatic setting.

[New aspects in thyroid cancer treatment : Highlights of the ASCO Annual Meeting 2018]. / Neue Aspekte in der Therapie von Schilddrüsenkarzinomen : Highlights vom ASCO-Kongress 2018.

Whereas surgical treatment of thyroid carcinoma plays an important role especially in the early stages, a multimodal approach is pursued in the palliative setting, which, in addition to classical chemotherapy primarily involves treatment with tyrosine kinase inhibitors. An analysis of clinical trials and studies presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2018 is presented. In particular, studies on the treatment of radioiodine-refractory differentiated thyroid cancer, anaplastic thyroid cancer and immunotherapy were selected and analyzed. Clinically and preclinically relevant studies are presented and critically interpreted in this review.

Current studies of immunotherapy in head and neck cancer.

BACKGROUND: Recently, enormous progress in cancer therapy has been achieved by the use of immune checkpoint inhibitors. Activating the body's own immune system has added a novel and powerful therapeutic option for the treatment of melanoma and lung cancer. Furthermore, the potential use of immunotherapy is being extensively explored also in other malignancies. OBJECTIVE OF REVIEW: This review summarises current clinical studies using immune checkpoint modulators for the treatment of head and neck cancer (HNSCC). TYPE OF REVIEW: Systematic review. SEARCH STRATEGY: A PubMed search from 2010 onwards was performed for the use of immune checkpoint inhibitors in clinical trials of HNSCC. An equivalent search was performed at clinicaltrials.gov. Additionally, the abstracts from the annual meetings of the ASCO, ESMO and AACR were screened. RESULTS: A total of 45 relevant studies using immune checkpoint inhibitors in HNSCC were identified. In the majority of these studies, antagonistic antibodies targeting the immune checkpoint receptors PD-1 are used either solely or combined, mostly with other immunomodulatory antibodies, such as inhibitors of CTLA-4. Most studies are still recruiting patients (26/45). In the primary setting, we identified 16 studies using checkpoint inhibition as neoadjuvant/adjuvant modality for treatment with curative intent. The response rate upon treatment with PD-1 antagonists in relation to the PD-L1 status is being investigated in 12 trials. Novel immune checkpoint modulators combined with the inhibition of the PD-1/PD-L1 axis or CTLA-4 have been set up in six trials. So far, only four studies that use immune checkpoint inhibition in HNSCC have presented results and all of these explored the inhibition of the PD-1/PD-L1 axis. The studies demonstrated overall response rates (ORR) in the range of 20%. These preliminary data suggest that a PD-L1 expression ≥1% is associated with a higher response rate compared to a PD-L1 expression ≤1%. The anti-PD-1-antibody pembrolizumab extended the duration of response in recurrent and/or metastatic (R/M) HNSCC (by approximately 53 weeks) in a phase Ib study. Therefore, pembrolizumab was granted accelerated approval for the treatment of platinum refractory R/M HNSCC by the FDA. CONCLUSION: Numerous clinical trials are addressing the suitability and efficacy of immune checkpoint modulators in HNSCC with the predominant targets being the established immune checkpoint receptors PD-1/PD-L1 and CTLA-4. Recently, presented results have shown a survival benefit, a favourable safety profile and an extended duration of response in favour of using immune checkpoint modulation in R/M HNSCC.

Oncologic treatment landscape for head and neck squamous cell carcinoma : Treatment infrastructure in German-speaking countries.

BACKGROUND: The treatment of head and neck squamous cell carcinoma (HNSCC) is highly complex and requires a multimodal approach. However, guidelines for the treatment of most forms of HNSCC do not exist in German-speaking countries with the exception of oral cavity cancer. The aim of this cross-sectional study was to describe the current treatment landscape and infrastructure in German-speaking countries. METHODS: From November 2013 to July 2014, 204 departments of otorhinolaryngology (ORL) in Germany, Austria, and the German-speaking part of Switzerland were contacted and invited to take part in a web-based survey on the treatment of HNSCC. In order to cover the study in its entirety, we published three consecutive papers of which this paper is the first. RESULTS: In all, 62 treatment centers (30.4 %) participated in the survey. These centers included 21 university hospitals, 16 certified cancer centers, and 35 large centers, which diagnose at least 75 HNSCC patients annually. In 91.9 % of all cases, there were outpatient consultation hours (that were monodisciplinary in 61.4 %). A multidisciplinary tumor board was existent in 98.4 % of the cases. Of 62 ORL departments, 50 had a hospital cancer registry, 41 of 62 conducted oncological studies, and 35 of 62 assessed their patients' quality of life. CONCLUSION: The infrastructure of the treatment for HNSCC can be considered mostly well-developed and supports interdisciplinary cooperation. Potential improvements can be made regarding the standardization of tumor boards, the participation in clinical trials, and the availability of cancer registries and the data gathered therein.

Postoperative antibiotic prophylaxis in clean-contaminated head and neck oncologic surgery: a retrospective cohort study.

Antibiotic prophylaxis is commonly used in head and neck oncologic surgery, due to the clean-contaminated nature of these procedures. There is a wide variety in the use of prophylactic antibiotics regarding the duration of application and the choice of agent. The purpose of this study was to determine whether short-term or long-term antibiotic prophylaxis has an impact on the development of head and neck surgical wound infection (SWI). Retrospective chart review was carried out in 418 clean-contaminated head and neck surgical oncology cases at our department. More than 50 variables including tumour type and stage, type of surgical treatment, co-morbidities, duration and choice of antibiotic prophylaxis, and the incidence of SWI were analysed. Following descriptive data analysis, Chi square test by Pearson and Fisher's exact test were used for statistical evaluation. Fifty-eight of the 418 patients (13.9 %) developed SWI. Patients with advanced disease and tracheotomy showed a significantly higher rate of SWI than those with early stage disease and without tracheotomy (p = 0.012 and p = 0.00017, respectively). However, there was no significant difference between the SWI rates in the short term and long term treatment groups (14.6 and 13.2 %, respectively; p = 0.689). Diabetes and body weight were not found to be risk factors for SWI. Long-term antibiotic prophylaxis was not associated with a decrease in SWI in the entire cohort of patients undergoing clean-contaminated major head and neck oncologic surgery. Our data confirmed the extent of surgery and tracheotomy as being risk factors for postoperative SWI.

Timing of neck dissection in patients undergoing transoral robotic surgery for head and neck cancer.

BACKGROUND: Oncologic transoral robotic surgery (TORS) requires in most cases the concurrent or staged surgical treatment of the regional lymph nodes in the neck as well. The purpose of this study was to determine whether the timing of the regional lymphadenectomy (neck dissection) has an impact on the surgical outcomes and on the complication rates. METHODS: Single-institution, prospective case series with internal control group. Twenty-one patients underwent TORS and appropriate neck dissection concurrently (control group), while 20 patients underwent neck dissection in a timely staged fashion, 8.4 days (median; range, 3-28 days) following their TORS procedure (experimental group). Outcome measures included nodal yield, intraoperative pharyngocervical fistula formation, postoperative fistula formation, postoperative bleeding from the primary and from the neck dissection site, haematoma, seroma, and infection. RESULTS: Nodal yield values, as the oncologic quality indicator of a neck dissection, were comparable in the experimental and in the control group. Complication rates did not differ between the groups: intraoperative and postoperative fistula formation, postoperative bleeding, haematoma and seroma rates were similarly low in the two groups. There was no infection in either group. CONCLUSIONS: In the present cohort of 41 TORS-patients, the timing of neck dissection did not make a significant difference in the outcomes. We suggest therefore that aspiring and established TORS-teams do not restrict their appropriate indications due to robotic slot and theatre time constraints, but perform each indicated TORS-case as soon as possible within their given systems, even if the neck dissections cannot be done on the same day.

[The most important study results of primary chemoradiation for head and neck squamous cell carcinoma : highlights of the ASCO Meeting 2013]. / Die wichtigsten Studienergebnisse der primären Radio-Chemo-Therapie von Kopf-Hals-Tumoren : Highlights des ASCO-Meetings 2013.

Primary concomitant and sequential chemoradiation is a commonly used therapeutic strategy for head and neck squamous cell carcinoma. At the annual meeting of the American Society of Clinical Oncology 2013 numerous trial results were presented. A selection of the most important trials will be summarized in this article. This year several results from phase II and III trials in concomitant and sequential therapy were demonstrated.

[Therapy of recurrent and metastatic squamous cell carcinoma of the head and neck : highlights of the ASCO Meeting 2013]. / Therapie der Rezidiv- und Fernmetastasen bei Plattenepithelkarzinomen des Kopf- und Halsbereichs : Highlights des ASCO-Meetings 2013.

In many cases squamous cell carcinoma of the head and neck is already in an advanced stage when initially diagnosed. Despite definitive treatment, loco-regional recurrences and metastases are common and patients ultimately require systemic treatment. Epidermal growth factor receptor (EGFR) inhibitors have proven to significantly prolong survival and have therefore become the first line treatment in recurrent and metastatic squamous cell carcinoma of the head and neck in addition to platinum and 5-FU treatment. Good results have also been reported for EGFR inhibitors in cases where platinum-based treatment has failed. Further strategies, such as salvage surgery, platinum-based chemotherapy, targeted therapy, chemoradiation and reirradiation are currently under investigation to reduce toxicity and improve survival and health-related quality of life.

Expression of insulin-like growth factor II mRNA-binding protein 3 in squamous cell carcinomas of the head and neck.

BACKGROUND: Insulin-like growth factor II mRNA-binding protein 3 (IMP3) was found overexpressed in various cancer types suggesting its possible role in carcinogenesis. Analysis of IMP3 expression in head and neck squamous cell carcinomas (HNSCC) is rare so that we evaluated it using tissue microarray method. METHOD: Immunohistochemical analysis of IMP3 was performed on samples from over 400 patients. The expression was measured semiquantitative, subsequently divided into four categories (negative, weak, medium, or strong) and correlated with several available clinicopathologic parameters. RESULTS: For HNSCC, positive IMP3 expression was observed in patients with all tumor stages (pT1-4) and nodal stages (pN0-3), showing also significant statistical correlation (P=0.023 and P=0.0013, respectively). No further correlations were found. Separate analysis according to tumor localization (oral cavity, oropharyngeal, and laryngeal) showed a significant correlation of positive IMP3 expression and overall survival (P=0.038) only in patients with tumors of the oral cavity. Multivariate analysis showed IMP3 as an independent predictive marker for oral squamous cell carcinomas (OSCC). CONCLUSION: Insulin-like growth factor II mRNA-binding protein 3 (IMP3) expression might be used as an independent prognostic factor in the subgroup of OSCC.

[New aspects of current therapeutic strategies in oropharyngeal carcinoma: highlights of the 2012 ASCO meeting]. / Neue Aspekte zur aktuellen Therapie von Oropharynxkarzinomen: Highlights vom ASCO-Kongress 2012.

Beside the surgical treatment of head and neck cancer, the concept of organ and function preserving therapy of locally advanced HNSCC (head and neck squamous cell carcinoma) especially of oropharyngeal origin is becoming increasingly important. The comparison of induction chemotherapy plus chemoradiation and primary concomitant chemoradiation has recently been the subject of randomized clinical trials. New combinations of different (chemo)radiation regimens and targeted therapies are also under investigation for HNSCC. Molecular markers predicting treatment efficacy as well as new potential targets are also being evaluated in several clinical trials. The good prognosis of HPV-associated HNSCC has sparked efforts to deintensify treatment to minimize therapy-related toxicities. The impact of specific therapies is growing due to the increasing incidence of young patients with HPV-positive carcinomas.

[New aspects in the therapy of recurrence and metastasis of head and neck cancer: highlights from the 2012 ASCO meeting]. / Neue Therapieaspekte bei Rezidiv und Fernmetastase des Kopf- und Hals-Karzinoms: Highlights vom ASCO-Kongress 2012.

The majority of patients with a squamous cell carcinoma of the head and neck region (HNSCC) initially present in a locally advanced stage of the disease. Despite aggressive protocols in first-line treatment, some of these patients develop locoregional recurrences or metastases and are, in particular, extraordinarily challenging for the multidisciplinary treatment team. Therefore, among resectability and prior therapy, age, performance status and individual expectations of the patient have to be taken into account. Apart from surgical options like salvage surgery, chemotherapy and target therapy as well as reirradiation are possible treatment concepts. Unfortunately, most treatment options offer only little to no survival benefit.

[The most important results on primary chemoradiation for head and neck squamous cell carcinoma: highlights from the 2012 ASCO meeting]. / Die wichtigsten Studienergebnisse der primären Radiochemotherapie von Kopf-Hals-Tumoren: Highlights vom ASCO-Meeting 2012.

Primary concomitant and sequential chemoradiation is a commonly used therapeutic strategy for head and neck squamous cell carcinoma. At the annual meeting of the 2012 American Society of Clinical Oncology numerous trial results were presented. A selection of the most important trials will be summarized in this article. This year, several important results from phase III trials-including the long awaited comparison of sequential and concomitant chemoradiation-were demonstrated.

[New aspects of primary radiochemotherapy in head and neck cancer. Highlights from the 2011 ASCO Congress]. / Neue Aspekte der primären Radiochemotherapie bei Kopf-Hals-Tumoren. Highlights vom ASCO-Kongress 2011.

Primary radiochemotherapy is a treatment option for patients with locally advanced or unresectable head and neck cancer. Compared to conventional radiotherapy, intensity-modulated radiotherapy (IMRT) is associated with fewer long-term toxicities and better quality of life. Whether IMRT improves local control in these patients needs to be further investigated. The risk factors and treatment toxicities must be taken into consideration and discussed with the patients. New approaches combining radiotherapy and biological targets are a treatment option. The implementation of these substances in treatment protocols is increasing. Sensitive and specific prognostic biomarkers for patient identification to optimize treatment selection are important, but reliable parameters are still missing.

[Fluorescein aspiration during induction of anaesthesia : complication preceding surgical treatment of cerebrospinal fluid fistula]. / Fluoreszeinaspiration während der Narkoseeinleitung : Komplikation vor operativer Sanierung einer Liqourfistel.

This case history deals with an 85-year-old patient who underwent surgery to treat rhinoliquorrhea. The patient aspirated a lutescent fluid shortly after anesthesia was administered. However, this fluid was not gastric juice but cerebrospinal fluid (CSF) running down the nasopharynx. The CSF had been stained with fluorescein prior to surgery in order to help localize the CSF fistula. This case of top down aspiration is discussed and preventive measures which can be employed in order to avoid similar complications in patients with rhinoliquorrhea are presented.

[Wegener's granulomatosis in ENT: clinical presentation, diagnosis and therapy]. / Die Wegener Granulomatose: Klinik, Diagnose und Therapie anhand eines Fallberichts und einer Literaturübersicht.

INTRODUCTION: Wegener's granulomatosis (WG) is a vasculitis that effects the upper and lower part of the respiratory tract and the kidneys. Untreated the disease results in death within weeks or months. The diagnosis is based on clinical criteria, level of antineutrophil cytoplasmatic antibodies (ANCA) and signs of granulomatous necrotizing vasculitis in histology. METHODS: A case of an 18-year-old woman with initially symptoms of bilateral "mastoiditis" and weakness of her facial nerve is described. In this case ANCA levels remained normal for 3 months and persistent otological symptoms were predominant. The further clinical course was characterized by neurological problems (Palsy Nn. VII, IX, XII and thrombosis of the right sigmoid sinus). The initial therapy consisted of Prednisone 100 mg and Cyclophosphamide 100 mg daily. The patient has been treated successfully with Methotrexate 20 mg 1 x/week and Prednisone 15 mg/die for 4 months now. CONCLUSION: A common clinical presentation of WG involves the upper respiratory tract. Therefore ENT-specialists should be familiar with the disease. Especially in cases of persistent signs of bilateral "Mastoiditis" and neurological symptoms WG should be ruled out as differential diagnosis. A close interdisciplinary cooperation is essential for therapy and follow-up, because systemic involvement is the limiting prognostic factor.

Antimicrobial defence mechanisms of the human parotid duct.

The parotid duct transports saliva from the gland into the oral cavity. However, its immune response properties, along with the secretion and moistening principles of the duct, have not yet been fully investigated. These properties may play an important role in protecting the parotid gland from infection and also prevent development of sialodocholithiasis, as the parotid duct -- in contrast to the submandibular salivary duct -- is often free of duct concrements. Up to now, only the parotid gland has been investigated, without regard to its duct. The present study analyses the structures of the parotid duct in their relations to antimicrobial defence mechanisms and rheological properties. Investigations were performed on 23 parotid ducts using histological, histochemical and immunohistochemical methods. Epithelial and goblet cells of the parotid duct synthesize a complex mucous layer that covers the epithelium. The viscosity is influenced by secreted mucins and TFF peptides. This layer contains carbohydrates including N-acetyl-glucosamine, N-acetyl-galactosamine, galactose, mannose, fucose and sialic acids. The lamina propria contains granulocytes, T lymphocytes and macrophages. IgA, produced by plasma cells in the subepithelial layer, is frequently integrated in the secretory product. Synthesized mucins, TFF peptides, carbohydrates and immunoglobulins form a complex layer that can be expected to prohibit infection and enables salivary flow. Our study demonstrates that the steady secretion of the parotid gland, together with the ductal cellular and biochemical immune protection system, is likely to thwart ascending infections in the parotid duct and gland.

[Assessment of motivational changes in tinnitus sufferers. A study of the transtheoretical model]. / Erfassung der Veränderungsmotivation bei Tinnituspatienten. Eine Studie zum transtheoretischen Modell.

OBJECTIVES: Cognitive-behavioural treatment of chronic tinnitus needs active cooperation and motivation in patients. The transtheoretical model (TTM) defines the behavioural change using six different stages of change (SoC). In this study, we examined SoC in patients with tinnitus via a new self-rating instrument. SAMPLE AND METHODS: An item-pool, consisting of 48 questions, was administered to 125 tinnitus sufferers in a cross-sectional study. In addition to data on tinnitus history, the tinnitus strain (THI, German: TB-12), scores of anxiety and depression (HADS-D), and life quality (SF-12) were assessed. RESULTS: Four SoC could be identified empirically: (1) precontemplation, (2) contemplation/preparation, (3) action/maintenance, and (4) termination. Associations of the SoC with socio-demographic and tinnitus related data, as well as with the instruments applied, conformed with the theory. CONCLUSIONS: The results confirm the transfer of SoC theory to patients with tinnitus.