Immune checkpoint inhibitors for POLE or POLD1 proofreading-deficient metastatic colorectal cancer.

BACKGROUND: POLE and POLD1 proofreading deficiency (POLE/D1pd) define a rare subtype of ultramutated metastatic colorectal cancer (mCRC; over 100 mut/Mb). Disease-specific data about the activity and efficacy of immune checkpoint inhibitors (ICIs) in POLE/D1pd mCRC are lacking and it is unknown whether outcomes may be different from mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) mCRCs treated with ICIs. PATIENTS AND METHODS: In this global study, we collected 27 patients with mCRC harboring POLE/D1 mutations leading to proofreading deficiency and treated with anti-programmed cell death-ligand 1 alone +/- anti-cytotoxic T-lymphocyte antigen-4 agents. We collected clinicopathological and genomic characteristics, response, and survival outcomes after ICIs of POLE/D1pd mCRC and compared them with a cohort of 610 dMMR/MSI-H mCRC patients treated with ICIs. Further genomic analyses were carried out in an independent cohort of 7241 CRCs to define POLE and POLD1pd molecular profiles and mutational signatures. RESULTS: POLE/D1pd was associated with younger age, male sex, fewer RAS/BRAF driver mutations, and predominance of right-sided colon cancers. Patients with POLE/D1pd mCRC showed a significantly higher overall response rate (ORR) compared to dMMR/MSI-H mCRC (89% versus 54%; P = 0.01). After a median follow-up of 24.9 months (interquartile range: 11.3-43.0 months), patients with POLE/D1pd showed a significantly superior progression-free survival (PFS) compared to dMMR/MSI-H mCRC [hazard ratio (HR) = 0.24, 95% confidence interval (CI) 0.08-0.74, P = 0.01] and superior overall survival (OS) (HR = 0.38, 95% CI 0.12-1.18, P = 0.09). In multivariable analyses including the type of DNA repair defect, POLE/D1pd was associated with significantly improved PFS (HR = 0.17, 95% CI 0.04-0.69, P = 0.013) and OS (HR = 0.24, 95% CI 0.06-0.98, P = 0.047). Molecular profiling showed that POLE/D1pd tumors have higher tumor mutational burden (TMB). Responses were observed in both subtypes and were associated with the intensity of POLE/D1pd signature. CONCLUSIONS: Patients with POLE/D1pd mCRC showed more favorable outcomes compared to dMMR/MSI-H mCRC to treatment with ICIs in terms of tumor response and survival.

Tumor mutational burden is predictive of response to immune checkpoint inhibitors in MSI-high metastatic colorectal cancer.

BACKGROUND: Microsatellite instability (MSI) is a biomarker for response to immune checkpoint inhibitors (ICPIs). PD-1 inhibitors in metastatic colorectal carcinoma (mCRC) with MSI-high (MSI-H) have demonstrated a high disease control rate and favorable progression-free survival (PFS); however, reported response rates to pembrolizumab and nivolumab are variable and often <50%, suggesting that additional predictive biomarkers are needed. METHODS: Clinicopathologic data were collected from patients with MSI-H mCRC confirmed by hybrid capture-based next-generation sequencing (NGS) treated with PD-1/L1 inhibitors at five institutes. Tumor mutational burden (TMB) was determined on 0.8-1.1 Mb of sequenced DNA and reported as mutations/Mb. Potential biomarkers of response and time to progression were analyzed by univariate and multivariate analyses. Once TMB was confirmed as a predictive biomarker, a larger dataset of 18 140 unique CRC patients was analyzed to define the relevance of the identified TMB cut-point. RESULTS: A total of 22 patients were treated with PD-1/L1 inhibitors including 19 with pembrolizumab monotherapy. Among tested variables, TMB showed the strongest association with objective response (OR; P < 0.001) and PFS, by univariate (P < 0.001) and multivariate analysis (P < 0.01). Using log-rank statistics, the optimal predictive cut-point for TMB was estimated between 37 and 41 mutations/Mb. All 13 TMBhigh cases responded, while 6/9 TMBlow cases had progressive disease. The median PFS for TMBhigh has not been reached (median follow-up >18 months) while the median PFS for TMBlow was 2 months. A TMB of 37.4 mutations/Mb in a large MSI-H mCRC population (821/18, 140 cases; 4.5%) evaluated by NGS corresponded to the 35th percentile cut-point. CONCLUSIONS: TMB appears to be an important independent biomarker within MSI-H mCRC to stratify patients for likelihood of response to ICPIs. If validated in prospective studies, TMB may play an important role in guiding the sequencing and/or combinations of ICPIs in MSI-H mCRC.

Cross-sectional increase of adherence to multidisciplinary tumor board decisions.

BACKGROUND: Cancer research has made great progress in the recent years. With the increasing number of options in diagnosis and therapy the implementation of tumorboards (TUBs) has become standard procedure in the treatment of cancer patients. Adherence tests on tumor board decisions are intended to enable quality assurance and enhancement for work in tumor boards in order to continuously optimize treatment options for cancer patients. METHODS: Subject of this study was the adherence of the recommendations made in three of 14 tumorboards, which take place weekly in the Center for Integrated Oncology (CIO) at the University Hospital Bonn. In total, therapy recommendations of 3815 patient cases were checked on their implementation. A classification into four groups has been made according to the degree of implementation. A second classification followed regarding the reasons for differences between the recommendation and the therapy which the patient actually received. RESULTS: The study showed that 80.1% of all recommendations in the three TUBs were implemented. 8.3% of all recommendations showed a deviance. Most important reasons for the deviances were patient wish (36.5%), patient death (26%) and doctoral decision, due to the patient's comorbidities or side effects of the treatment (24.1%).Interestingly, deviance in all three tumor boards in total significantly decreased over time. CONCLUSIONS: Aim of the study was to clarify the use of tumor boards and find approaches to make them more efficient. Based on the results efficiency might be optimized by increased consideration of patients` preferences, improved presentation of patient-related data, more detailed documentation and further structuring of the tumor board meetings.

RET fusions in a small subset of advanced colorectal cancers at risk of being neglected.

Background: Recognition of rare molecular subgroups is a challenge for precision oncology and may lead to tissue-agnostic approval of targeted agents. Here we aimed to comprehensively characterize the clinical, pathological and molecular landscape of RET rearranged metastatic colorectal cancer (mCRC). Patients and methods: In this case series, we compared clinical, pathological and molecular characteristics of 24 RET rearranged mCRC patients with those of a control group of 291 patients with RET negative tumors. RET rearranged and RET negative mCRCs were retrieved by systematic literature review and by taking advantage of three screening sources: (i) Ignyta's phase 1/1b study on RXDX-105 (NCT01877811), (ii) cohorts screened at two Italian and one South Korean Institutions and (iii) Foundation Medicine Inc. database. Next-generation sequencing data were analyzed for RET rearranged cases. Results: RET fusions were more frequent in older patients (median age of 66 versus 60 years, P = 0.052), with ECOG PS 1-2 (90% versus 50%, P = 0.02), right-sided (55% versus 32%, P = 0.013), previously unresected primary tumors (58% versus 21%, P < 0.001), RAS and BRAF wild-type (100% versus 40%, P < 0.001) and MSI-high (48% versus 7%, P < 0.001). Notably, 11 (26%) out of 43 patients with right-sided, RAS and BRAF wild-type tumors harbored a RET rearrangement. At a median follow-up of 45.8 months, patients with RET fusion-positive tumors showed a significantly worse OS when compared with RET-negative ones (median OS 14.0 versus 38.0 months, HR: 4.59; 95% CI, 3.64-32.66; P < 0.001). In the multivariable model, RET rearrangements were still associated with shorter OS (HR: 2.97; 95% CI, 1.25-7.07; P = 0.014), while primary tumor location, RAS and BRAF mutations and MSI status were not. Conclusions: Though very rare, RET rearrangements define a new subtype of mCRC that shows poor prognosis with conventional treatments and is therefore worth of a specific management.

Comprehensive genomic profiles of metastatic and relapsed salivary gland carcinomas are associated with tumor type and reveal new routes to targeted therapies.

BACKGROUND: Relapsed/metastatic salivary gland carcinomas (SGCs) have a wide diversity of histologic subtypes associated with variable clinical aggressiveness and response to local and systemic therapies. We queried whether comprehensive genomic profiling could define the tumor subtypes and uncover clinically relevant genomic alterations, revealing new routes to targeted therapies for patients with relapsed and metastatic disease. PATIENTS AND METHODS: From a series of 85 686 clinical cases, DNA was extracted from 40 µm of formalin-fixed paraffin embedded (FFPE) sections for 623 consecutive SGC. CGP was carried out on hybridization-captured, adaptor ligation-based libraries (mean coverage depth, >500×) for up to 315 cancer-related genes. Tumor mutational burden was determined on 1.1 Mb of sequenced DNA. All classes of alterations, base substitutions, short insertions/deletions, copy number changes, and rearrangements/fusions were determined simultaneously. RESULTS: The clinically more indolent SGC including adenoid cystic carcinoma, acinic cell carcinoma, polymorphous low-grade adenocarcinoma, mammary analog secretory carcinoma, and epithelial-myoepithelial carcinomas have significantly fewer genomic alterations, TP53 mutations, and lower tumor mutational burden than the typically more aggressive SGCs including mucoepidermoid carcinoma, salivary duct carcinoma, adenocarcinoma, not otherwise specified, carcinoma NOS, and carcinoma ex pleomorphic adenoma. The more aggressive SGCs are commonly driven by ERBB2 PI3K pathway genomic alterations. Additional targetable GAs are frequently seen. CONCLUSIONS: Genomic profiling of SGCs demonstrates important differences between traditionally indolent and aggressive cancers. These differences may provide therapeutic options in the future.

Hybrid capture-based genomic profiling of circulating tumor DNA from patients with estrogen receptor-positive metastatic breast cancer.

BACKGROUND: Genomic changes that occur in breast cancer during the course of disease have been informed by sequencing of primary and metastatic tumor tissue. For patients with relapsed and metastatic disease, evolution of the breast cancer genome highlights the importance of using a recent sample for genomic profiling to guide clinical decision-making. Obtaining a metastatic tissue biopsy can be challenging, and analysis of circulating tumor DNA (ctDNA) from blood may provide a minimally invasive alternative. PATIENTS AND METHODS: Hybrid capture-based genomic profiling was carried out on ctDNA from 254 female patients with estrogen receptor-positive breast cancer. Peripheral blood samples were submitted by clinicians in the course of routine clinical care between May 2016 and March 2017. Sequencing of 62 genes was carried out to a median unique coverage depth of 7503×. Genomic alterations (GAs) in ctDNA were evaluated and compared with matched tissue samples and genomic datasets of tissue from breast cancer. RESULTS: At least 1 GA was reported in 78% of samples. Frequently altered genes were TP53 (38%), ESR1 (31%) and PIK3CA (31%). Temporally matched ctDNA and tissue samples were available for 14 patients; 89% of mutations detected in tissue were also detected in ctDNA. Diverse ESR1 GAs including mutation, rearrangement and amplification, were observed. Multiple concurrent ESR1 GAs were observed in 40% of ESR1-altered cases, suggesting polyclonal origin; ESR1 compound mutations were also observed in two cases. ESR1-altered cases harbored co-occurring GAs in PIK3CA (35%), FGFR1 (16%), ERBB2 (8%), BRCA1/2 (5%), and AKT1 (4%). CONCLUSIONS: GAs relevant to relapsed/metastatic breast cancer management were identified, including diverse ESR1 GAs. Genomic profiling of ctDNA demonstrated sensitive detection of mutations found in tissue. Detection of amplifications was associated with ctDNA fraction. Genomic profiling of ctDNA may provide a complementary and possibly alternative approach to tissue-based genomic testing for patients with estrogen receptor-positive metastatic breast cancer.

Emergence of EGFR G724S mutation in EGFR-mutant lung adenocarcinoma post progression on osimertinib.

Mutations in the epidermal growth factor receptor (EGFR) are drivers for a subset of lung cancers. Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) recently approved for the treatment of T790M-positive non-small cell lung cancer (NSCLC); however, acquired resistance to osimertinib is evident and resistance mechanisms remain incompletely defined. The EGFR G724S mutation was detected using hybrid-capture based comprehensive genomic profiling (CGP) and a hybrid-capture based circulating tumor DNA (ctDNA) assays in two cases of EGFR-driven lung adenocarcinoma in patients who had progressed on osimertinib treatment. This study demonstrates the importance of both tissue and blood based hybrid-capture based genomic profiling at disease progression to identifying novel resistance mechanisms in the clinic.

[Interventional radiology in the head and neck region]. / Interventionelle Radiologie im Kopf-Hals-Bereich.

In interventional neuroradiology, endovascular embolization represents an important and helpful tool in the treatment of multiple head and neck diseases. These interventional procedures may be performed with curative intent, to reduce the surgical risk within a multimodal treatment concept, or to improve or at least maintain a good quality of life within a palliative therapy concept. In addition to a good understanding of disease pathology, knowledge of vascular anatomy, including collateral vessels and dangerous extracranial-intracranial anastomoses, is essential for successful treatment, as is implementation of an established technique using appropriate material. Indications for endovascular embolization are i. otherwise unmanageable bleeding (caused by e. g., trauma, vascular malformation, or tumor), ii. reduction of perioperative bleeding by preoperative embolization in case of a hypervascularized tumor, iii. selective induction of tumor necrosis by palliative embolization to enhance local tumor control. Major complications such as stroke, loss of vision, and cranial nerve palsy are mostly due to a lack of preinterventional evaluation. Regarding neurological deficits, interventions within the supply region of the external carotid artery have a complication rate below 1%.

Comprehensive genomic profiling of salivary mucoepidermoid carcinomas reveals frequent BAP1, PIK3CA, and other actionable genomic alterations.

Background: We sought to identify genomic alterations (GAs) in salivary mucoepidermoid carcinomas. Patients and methods: DNA was extracted from 48 mucoepidermoid carcinomas. Comprehensive genomic profiling (CGP) including the calculation to tumor mutational burden (TMB) was performed on hybridization-captured adaptor ligation-based libraries of 315 cancer-related genes plus introns from 28 genes frequently rearranged for cancer and evaluated for all classes of GAs. Results: A total of 183 GAs were found in 80 unique genes. High-grade tumors had more GAs (mean 5 ± 3.8) compared with low (2.3 ± 1.4) or intermediate (2.6 ± 1.5) (P = 0.019). TP53 GAs were seen in all tumor grades (41.7%) but were most common in high-grade malignancies (56%) (P = 0.047). CDKN2A GAs were seen in 41.6% of tumors. PI3K/mTOR pathway activation, including PI3KCA mutations, were more common in high grade (52%) than in low- and intermediate-grade tumors (4.3%) (P = 0.007). BAP1 GAs were observed in 20.8% of tumors and BRCA1/2 GAs present in 10.5% of specimens. ERBB2 amplifications were seen in only 8.3% of tumors. The TMB for this patient group was relatively low with only 5 (10%) of cases having greater than 10 mutations/megabase of sequenced DNA. Conclusion: CGP of salivary mucoepidermoid carcinomas revealed diverse GAs that may lead to customized treatment options for patients with these rare tumors.

Comprehensive genomic profiling of anal squamous cell carcinoma reveals distinct genomically defined classes.

BACKGROUND: Squamous cell cancers of the anal canal (ASCC) are increasing in frequency and lack effective therapies for advanced disease. Although an association with human papillomavirus (HPV) has been established, little is known about the molecular characterization of ASCC. A comprehensive genomic analysis of ASCC was undertaken to identify novel genomic alterations (GAs) that will inform therapeutic choices for patients with advanced disease. PATIENTS AND METHODS: Hybrid-capture-based next-generation sequencing of exons from 236 cancer-related genes and intronic regions from 19 genes commonly rearranged in cancer was performed on 70 patients with ASCC. HPV status was assessed by aligning tumor sequencing reads to HPV viral genomes. GAs were identified using an established algorithm and correlated with HPV status. RESULTS: Sixty-one samples (87%) were HPV-positive. A mean of 3.5 GAs per sample was identified. Recurrent alterations in phosphoinositol-3-kinase pathway (PI3K/AKT/mTOR) genes including amplifications and homozygous deletions were present in 63% of cases. Clinically relevant GAs in genes involved in DNA repair, chromatin remodeling, or receptor tyrosine kinase signaling were observed in 30% of cases. Loss-of-function mutations in TP53 and CDKN2A were significantly enhanced in HPV-negative cases (P < 0.0001). CONCLUSIONS: This is the first comprehensive genomic analysis of ASCC, and the results suggest new therapeutic approaches. Differing genomic profiles between HPV-associated and HPV-negative ASCC warrants further investigation and may require novel therapeutic and preventive strategies.

[Management of atypical cervical mycobacteriosis in childhood]. / Management der zervikalen atypischen Mykobakteriose im Kindesalter.

Atypical mycobacteriosis is a rare cause of cervical lymphadenitis that most frequently affects immunoincompetent children between the ages of 12 months and 5 years. The typical clinical manifestation is a painless unilateral cervical mass. The nonspecific clinical symptoms and laboratory parameters complicate diagnosis and, therefore, therapeutic management. Various therapeutic options, including surgery, antimycobacterial drug therapy and wait-and-scan approaches are discussed in the literature. Complete surgical excision has become the established treatment of choice. However, controlled randomized studies that clearly demonstrate the benefits of a particular type of therapy are lacking.

[Dacryocystorhinostomy as part of the interdisciplinary treatment of lacrimal duct]. / Dakryozystorhinostomie nach West in der interdisziplinären Behandlung von Tränenwegsstenosen.

INTRODUCTION AND METHODS: Epiphora, which leads to blurry vision, is the leading symptom for intra- and/or postsaccal lacrimal duct stenosis. Due to the anatomy of the tear duct system, which lies between the fields of ophthalmology and otorhinolaryngology, and due to newly available techniques in interventional radiology to diagnose and treat patients with intra- and postsaccal lacrimal duct stenosis, various methods for diagnosis and treatment are available. We report the results of 107 patients who underwent endonasal dacryocystorhinostomy (DCR) between 2005 and 2011. RESULTS: Prior to the DCR, dacryocystography was performed in 95 of the 107 patients. In 68 of these 95 cases, balloon dilatation was unsuccessful. Histological examination of 64 patients showed chronic inflammation in 61 patients, non-Hodgkin's lymphoma was diagnosed in 2 patients and aspergilloma in1 patient. Over a follow-up time of 6 months to a maximum of 7 years we revised 15 of 107 patients, due to reocclusion after removal of the stent. None of these patients showed recurrence of epiphora. DISCUSSION: In comparison to transcutaneous DCR, endonasal DCR has certain benefits: it is less invasive, no visible scars occur because of the endonasal approach, and the function of the lacrimal pump remains uneffected. Furthermore, the possibility of co-treatment of endonasal pathologies during DCR exists. We observed no serious adverse events in our study group and the success rate was similar to other studies.

[Analysis of quality of life outcome for nasopharyngeal carcinoma patients after treatment]. / Posttherapeutische Lebensqualität beim Nasopharynxkarzinom.

BACKGROUND: This retrospective study analysed patient characteristics and quality of live (QoL) for patients with nasopharyngeal carcinoma (NPC) after treatment. MATERIAL AND METHODS: A cross-sectional investigation was conducted to assess the QoL of 20 NPC patients with cancer-free survival of more than one year, which were treated with radiotherapy (RT) or chemoradiotherapy (RCT) during the period 2001-2009 at the University Hospital Bonn, Germany. The QoL was assessed by the FACT-NP (functional assessment of cancer therapy-nasopharyngeal) questionnaire. RESULTS: The median age of the patients was 57 ± 13 years and the male/female ratio was 2.33/1.3 (15%) patients were treated with RT and 17 (85%) with RCT. The global QoL was good in our patients. Xerostomia, chewing, decrease of gustatory sense, discontent with sexual life and ear problems were of major concern with the majority of patients and affected the QoL negatively. Pain, lost of working ability, emotional distress, or family problems were no significant factors. CONCLUSION: The expected reduction of QoL after treatment must be explained in detail to the NPC patient. The integration of the family and partner, an antidepressant therapy or psycho-oncological support can be useful and necessary.

[Sinonasal tract malignancies : a 14-year single institution experience]. / Maligne Erkrankungen des Sinunasaltrakts : Eine monoinstitutionelle Erfahrung von 1996 bis 2010.

BACKGROUND: With a worldwide annual incident rate of 1/200,000 sinonasal tract malignancies are a relatively rare disease. MATERIAL AND METHODS: All patients with sinonasal malignancies (n = 177) treated between 1996 and 2010 at the Department of Head and Neck Surgery, University of Bonn, Germany were analyzed retrospectively. Data on age, gender and incidence were available for all patients but other demographic data, treatment regimes and outcome were only analyzed for carcinomas. RESULTS: Carcinomas were the most frequent histological diagnosis (58%). Unspecific sinonasal symptoms lasted on average for 4.7 ± 5 months before primary diagnosis. Interestingly, 64% of patients with sinonasal carcinoma presented with locally advanced disease (T3-4) but only 15% displayed corresponding regional lymph node metastases. The overall 3-year survival rate was 61%. Patients solely needing surgical treatment displayed a better survival rate than patients receiving combined surgery and adjuvant treatment or definitive radio(chemo)therapy. Multivariate analysis revealed a T-stage classification as the only independent prognostic factor for 3-year survival. CONCLUSIONS: Due to unspecific symptoms most sinonasal malignancies are diagnosed at an advanced stage of the disease and despite multimodal therapies these tumors still have an unfavorable prognosis.

[Interdisciplinary emergency departments : first experiences from the ENT and head and neck perspective]. / Interdisziplinäre Notfallzentren : Erste Erfahrungen aus HNO-ärztlicher Sicht.

BACKGROUND: Centralized emergency departments are becoming a major source of health care in Germany. In this study, we evaluated the importance for ENT health care. METHODS: In a retrospective study, all ENT emergency patients between May and July 2011 were characterized by diagnosis, therapy, and urgency (measured using the Manchester Triage System [MTS]). General epidemiological data from the emergency department were recorded between 2009 and 2011. RESULTS: Between 2009 and 2011, 50,699 patients were treated in the centralized emergency department of the University Hospital Bonn. A total of 15,658 (30.8%) needed ENT health care. During May 2011 to July 2011, ENT emergency patients had not only a wide variety of diseases but also a broad range of ages (0-98 years). Using the MTS, emergency patients (4% acute emergencies) were identified and urgency was determined prior to first contact with the physician. CONCLUSION: ENT emergency care plays an important role for centralized emergency departments. Most of the patients have ENT diseases treatable as an outpatient in a single visit. MTS can be used to determine the appropriate level of urgency.

[CT rhinometry : a correlation of rhinomanometry and multiplanar computer tomography of the nasal cavity]. / CT-Rhinometrie : Korrelation der Rhinomanometrie mit multiplanarer Computertomographie der Nasenhaupthöhle.

BACKGROUND: Otorhinolaryngologists require new diagnostic methods to give further insight into the physiology of nasal breathing. The functional aspects of radiological data in the field of ENT have rarely been examined. This study compares computed tomography (CT) scan area measurements of the paranasal sinuses with physiological data from rhinomanometry. PATIENTS AND METHODS: In a retrospective study, paranasal CT scans from 36 patients were analysed for volume, width and hydraulic diameter of the five key regions of the nasal cavity (CT rhinometry) and compared to the active anterior rhinomanometric (RMM) results representing the gold standard in nasal flow description. RESULTS: The highest correlation between the rhinomanometric results and CT rhinometry was found at the internal ostium, followed by the diffuser region. The structures important for regulating nasal flow could thus be identified in the CT area data. CONCLUSION: CT rhinometry revealed structures important for nasal breathing, in addition to providing anatomical and topographical data. CT rhinometry measured volumes, width and hydraulic diameters of the nasal cavity correlated with measurements of transnasal flow.

[Treatment results of nasopharyngeal carcinoma in adults]. / Ergebnisse beim Nasopharynxkarzinom im Erwachsenenalter.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a rare tumor entity in Germany in contrast to endemic countries in Asia or Africa. This retrospective study investigated patient characteristics and prognostic factors with respect to different NPC treatment strategies. PATIENTS AND METHODS: A total of 63 NPC patients treated during the period 1990-2009 at the University Hospital Bonn, Germany, were included. RESULTS: The median age of the patients was 56.4 years, the male:female ratio was 3.2:1, 23.8% were in Union Internationale Contre le Cancer (UICC) stage I/II and 76.2% were in stage III/IV. Most of the carcinomas were WHO type III (57.1%), followed by World Health Organization (WHO) type II (33.3%) and at last WHO type I (9.6%). The 5-year overall survival rate after concomitant chemoradiotherapy (RCT) was 75% and after radiotherapy (RT) 60%. The mortality rate increased by 3.5 times with each increase in T-stage (p ≤ 0.047). The recurrence rate (RR) after RCT was 34% and after RT alone 68% (p ≤ 0.04). Tumor ablation increased the RR significantly (p ≤ 0.047). CONCLUSION: Combined chemotherapy and RT is an effective treatment of NPC disease and clearly superior to RT alone. Tumor ablation before RCT/RT worsens the prognosis and is now obsolete.

[Facial impalement in childhood : obtain an overview before actionism]. / Kraniofaziale Pfählungsverletzung im Kindesalter : Überblick vor Aktionismus.

Facial impalement in childhood is very rare. In most cases, it is caused by accident. We present two young patients who suffered a facial impalement injury and were treated in the interdisciplinary emergency room of the University Hospital Bonn, Germany. The degree of injury could not be completely determined during the first examination. Serious complications could be excluded after examination via computed tomography (CT) and surgical exploration. The indication to use CT or magnetic resonance imaging in childhood has to be considered in order to obtain full and exact information about the extent of injury.

[Cystic lesion in the area of the vestibular folds]. / Zystische Raumforderung im Bereich der Taschenfalten.

Warthin tumor is the second most frequently seen benign tumor of the salivary glands and is generally located in the parotid gland. Although extraparotideal manifestations in the small salivary glands are rare, the occurrence of cystic lesions in the area of the nasopharynx, eyelid, oral cavity or vestibular folds should include the Warthin tumor in the differential diagnosis. The therapy of choice is complete surgical tumor resection.