Treatment response of advanced HNSCC towards immune checkpoint inhibition is associated with an activated effector memory T cell phenotype.

Locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) is associated with a poor prognosis. The introduction of PD-1 inhibitors has led to a significant improvement in survival, but only a subpopulation of patients responds to therapy. Current biomarkers cannot reliably identify these patients. The identification of biomarkers for the prediction and monitoring of immunotherapy is therefore of great importance. In this study, we characterized lymphocyte subsets in the peripheral blood of HNSCC patients under PD-1 inhibition. Patients with primary response (n=11) to PD-1 inhibition showed an increase of the CD3+ effector memory (CD3/EM) population and an elevated expression of the activation marker CD69 in CD3+ T cells, particularly in the CD3/EM subpopulation at 3 months when treatment response was assessed. In contrast, patients with primary treatment failure and progressive disease (n=9) despite PD-1 inhibition had lower absolute lymphocyte counts and an increased expression of CTLA-4 in CD3+ T cells at the time of treatment failure compared with baseline, particularly in CD4+ and CD8+ effector memory populations. Our results demonstrate that HNSCC patients' response to immune checkpoint inhibition shows a distinct immune signature in peripheral blood, which could help identify refractory patients earlier. Furthermore, strategies to overcome primary therapy failure by inducing a beneficial T cell phenotype or adding alternative immune checkpoint inhibitors could improve response rates and survival of HNSCC patients.

TOFIMS mass spectrometry-based immunopeptidomics refines tumor antigen identification.

T cell recognition of human leukocyte antigen (HLA)-presented tumor-associated peptides is central for cancer immune surveillance. Mass spectrometry (MS)-based immunopeptidomics represents the only unbiased method for the direct identification and characterization of naturally presented tumor-associated peptides, a key prerequisite for the development of T cell-based immunotherapies. This study reports on the implementation of ion mobility separation-based time-of-flight (TOFIMS) MS for next-generation immunopeptidomics, enabling high-speed and sensitive detection of HLA-presented peptides. Applying TOFIMS-based immunopeptidomics, a novel extensive benignTOFIMS dataset was generated from 94 primary benign samples of solid tissue and hematological origin, which enabled the expansion of benign reference immunopeptidome databases with > 150,000 HLA-presented peptides, the refinement of previously described tumor antigens, as well as the identification of frequently presented self antigens and not yet described tumor antigens comprising low abundant mutation-derived neoepitopes that might serve as targets for future cancer immunotherapy development.

Prospective Evaluation of a Tumor Control Probability Model Based on Dynamic 18F-FMISO PET for Head and Neck Cancer Radiotherapy.

Our purpose was to evaluate an imaging parameter-response relationship between the extent of tumor hypoxia quantified by dynamic 18F-fluoromisonidazole (18F-FMISO) PET/CT and the risk of relapse after radiotherapy in patients with head and neck cancer. Methods: Before a prospective cohort of 25 head and neck cancer patients started radiotherapy, they were examined with dynamic 18F-FMISO PET/CT 0-240 min after tracer injection. 18F-FMISO image parameters, including a hypoxia metric, MFMISO, derived from pharmacokinetic modeling of dynamic 18F-FMISO and maximum tumor-to-muscle ratio (TMRmax) at 4 h after injection, gross tumor volume (GTV), relative hypoxic volume based on MFMISO, and a logistic regression model combining GTV and TMRmax, were assessed and compared with a previous training cohort (n = 15). Dynamic 18F-FMISO was used to validate a tumor control probability model based on MFMISO The prognostic potential with respect to local control of all potential parameters was validated using the concordance index for univariate Cox regression models determined from the training cohort, in addition to Kaplan-Meier analysis including the log-rank test. Results: The tumor control probability model was confirmed, indicating that dynamic 18F-FMISO allows stratification of patients into different risk groups according to radiotherapy outcome. In this study, MFMISO was the only parameter that was confirmed as prognostic in the independent validation cohort (concordance index, 0.71; P = 0.004). All other investigated parameters, such as TMRmax, GTV, relative hypoxic volume, and the combination of GTV and TMRmax, were not able to stratify patient groups according to outcome in this validation cohort (P = not statistically significant). Conclusion: In this study, the relationship between MFMISO and the risk of relapse was prospectively validated. The data support further evaluation and external validation of dynamic 18F-FMISO PET/CT as a promising method for patient stratification and hypoxia-based radiotherapy personalization, including dose painting.

HPV vaccination as preventive approach for recurrent respiratory papillomatosis - a 22-year retrospective clinical analysis.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a rare, benign disease of the aerodigestive tract, especially the larynx, caused by infection with the human papillomavirus (HPV) types 6 or 11. Current management focuses on surgical debulking with microdebrider of papillomatous lesions with or without concurrent adjuvant therapy, e.g. Cidofovir®. This retrospective study evaluates the results of patients treated at a department of the university clinic between 1990 and 2012 and compares the results of the conventional treatment with a new treatment approach using adjuvant vaccination with Gardasil®. METHODS: A retrospective Kaplan Maier analysis of n = 24 patients diagnosed and treated with RPR was performed. The records were reviewed for gender, age at the time of first manifestation of disease and time to recurrence. RESULTS: Only n = 2 (15.4%) of the n = 13 vaccinated patients developed a recurrence of the disease after a mean time of 54.9 months (SD: 9.5 months). All patients who were not vaccinated (n = 11; 100%) developed a relapse after a mean time of 12.3 months (SD: 9.72 months). CONCLUSION: We propose that adjuvant HPV vaccination with Gardasil® might have a preventive effect in RRP by occluding new papilloma formation.

Low plasma protein Z levels are associated with an increased risk for perioperative bleedings.

BACKGROUND AND OBJECTIVES: Protein Z (PZ) deficiency has been implicated both in bleeding diatheses and in thrombophilia. Considering its ambiguous nature and the conflicting clinical data so far, we set out to evaluate the impact of low PZ on perioperative bleeding in patients who underwent surgical (ENT) interventions involving a high risk of bleeding. PATIENTS AND METHODS: After exclusion of other coagulation disorders, 154 Patients were stratified into quartiles according to PZ plasma concentrations to evaluate the relation between PZ and bleeding complications. RESULTS: Low PZ levels were associated with increased blood loss (P < .001), increased need for blood transfusions (P < .001), and a higher rate of surgical revisions (P = .009) in a concentration-dependent fashion. Low PZ caused earlier (within 24 hours) and repetitive bleedings (P = .005). The number of major bleeding episodes was significantly increased when low PZ was combined with bleeding history (P < .05). Finally, ROC analyses confirmed the predictive value of low PZ for bleeding complications and PZ-thresholds for clinical practice were determined. CONCLUSIONS: Low PZ appears to be an underestimated risk factor for perioperative bleeding. Determination of PZ plasma concentrations might be useful in the preoperative workup in patients with a bleeding history, when detailed clotting analyses remain inconclusive.

SDF-1/CXCR4 expression is an independent negative prognostic biomarker in patients with head and neck cancer after primary radiochemotherapy.

INTRODUCTION: Preclinical and clinical data suggest that the chemokine pathway governed by SDF-1 and CXCR4 contributes to a resistant phenotype. This retrospective biomarker study aims to explore the specific prognostic value of SDF-1 and CXCR4 expression in locally advanced head and neck squamous cell carcinomas (HNSCC) treated with primary radiochemotherapy (RT-CT). MATERIAL AND METHODS: Biopsies from 141 HNSCC tumours of the oral cavity, oropharynx and hypopharynx were evaluated for SDF-1 and CXCR4 expression by immunofluorescence. SDF-1 and CXCR4 expression was correlated with clinico-pathological characteristics and outcome after RT-CT. RESULTS: Patients with tumours exhibiting overexpression of intracellular SDF-1 and CXCR4 have a higher risk for loco-regional relapse and a worse overall survival after RT-CT (multivariate analysis, hazard ratio 2.33, CI [1.18-4.62], p = 0.02 and hazard ratio 2.02, CI [1.13-3.59], p = 0.02, respectively). Similar results were observed when only the subgroup of HPV DNA negative patients were analysed (hazard ratio 2.23 and 2.16, p = 0.02 and p = 0.01, respectively). CONCLUSIONS: Our data support the importance of SDF-1 and CXCR4 expression for loco-regional control and overall survival in HNSCC after primary radiochemotherapy. Prospective multivariate validation and further studies into CXCR4 inhibition to overcome radiation resistance are warranted.

Geometric analysis of loco-regional recurrences in relation to pre-treatment hypoxia in patients with head and neck cancer.

INTRODUCTION: A previous pattern-of-failure study has suggested that up to 50% of the loco-regional failures (LRF) in head and neck squamous cell carcinoma (HNSCC) occur outside the initial hypoxic volume determined by [18F]-fluoromisonidazole-PET ([18F]-FMISO-PET). The aim of the present analysis was to correlate spatial patterns of failure with respect to the pretherapeutic dynamic [18F]-FMISO-PET/CT in HNSCC after radiochemotherapy (RCT). MATERIAL AND METHODS: Within a running phase 2 trial using [18F]-FMISO-PET imaging prior to RCT in HNSCC patients (n = 54), we have observed so far 11 LRF with a minimum follow-up of 12 months. For nine patients, LRF imaging (CT or [18F]-FDG-PET/CT) for pattern-of-failure analysis was available. Analysis included the static 4-h hypoxic subvolume (VH) as well as a M-parameter volume (VM), which is derived from modeling of dynamic PET. Deformable image registration of the CT scan with the recurrent tumor to the pre-treatment [18F]-FMISO-PET/CT and the planning CT was done to quantify the hypoxic subvolumes compared to the recurrent tumor volume. Moreover, a point-of-origin analysis was performed. RESULTS: A total of five local, two regional and two loco-regional recurrences were detected. After deformable image registration of the CT scan with the recurrent tumor to the pre-treatment [18F]-FMISO-PET/CT and the planning CT, a significant overlap of the recurrence volume with [18F]-FMISO-positive subvolumes in the initial gross tumor volume (GTV) was observed. Median overlap of 40.2%, range 9.4-100.0%, for VH and 49.0%, range 4.4-96.4%, for VM was calculated. The point-of-origin analysis showed median distances of 0.0 mm, range 0.0-11.3 mm to VH and 8.6 mm, range 0.0-15.5 mm to VM, respectively. CONCLUSIONS: Our data suggest that loco-regional recurrences after RCT originate from the initial GTV (primary tumor and/or lymph node metastases) containing hypoxic subvolumes, which supports the concept of hypoxia imaging-based dose escalation.

Overlap of highly FDG-avid and FMISO hypoxic tumor subvolumes in patients with head and neck cancer.

BACKGROUND: PET imaging may be used to personalize radiotherapy (RT) by identifying radioresistant tumor subvolumes for RT dose escalation. Using the tracers [18F]-fluorodeoxyglucose (FDG) and [18F]-fluoromisonidazole (FMISO), different aspects of tumor biology can be visualized. FDG depicts various biological aspects, e.g., proliferation, glycolysis and hypoxia, while FMISO is more hypoxia specific. In this study, we analyzed size and overlap of volumes based on the two markers for head-and-neck cancer patients (HNSCC). MATERIAL AND METHODS: Twenty five HNSCC patients underwent a CT scan, as well as FDG and dynamic FMISO PET/CT prior to definitive radio-chemotherapy in a prospective FMISO dose escalation study. Three PET-based subvolumes of the primary tumor (GTVprim) were segmented: a highly FDG-avid volume VFDG, a hypoxic volume on the static FMISO image acquired four hours post tracer injection (VH) and a retention/perfusion volume (VM) using pharmacokinetic modeling of dynamic FMISO data. Absolute volumes, overlaps and distances to agreement (DTA) were evaluated. RESULTS: Sizes of PET-based volumes and the GTVprim are significantly different (GTVprim>VFDG>VH >VM; p < .05). VH is covered by VFDG or DTAs are small (mean coverage 74.4%, mean DTA 1.4 mm). Coverage of VM is less pronounced. With respect to VFDG and VH, the mean coverage is 48.7% and 43.1% and the mean DTA is 5.3 mm and 6.3 mm, respectively. For two patients, DTAs were larger than 2 cm. CONCLUSIONS: Hypoxic subvolumes from static PET imaging are typically covered by or in close proximity to highly FDG-avid subvolumes. Therefore, dose escalation to FDG positive subvolumes should cover the static hypoxic subvolumes in most patients, with the disadvantage of larger volumes, resulting in a higher risk of dose-limiting toxicity. Coverage of subvolumes from dynamic FMISO PET is less pronounced. Further studies are needed to explore the relevance of mismatches in functional imaging.

Prognostic value of dynamic hypoxia PET in head and neck cancer: Results from a planned interim analysis of a randomized phase II hypoxia-image guided dose escalation trial.

BACKGROUND AND PURPOSE: To prospectively assess the prognostic value of tumour hypoxia determined by dynamic [18F]Fluoromisonidazole (dynFMISO) PET/CT, and to evaluate both feasibility and toxicity in patients with locally advanced squamous cell carcinomas of the head and neck (LASCCHN) treated with dynFMISO image-guided dose escalation (DE) using dose-painting by contours. PATIENTS AND METHODS: We present a planned interim analysis of a randomized phase II trial. N=25 patients with LASCCHN received baseline dynFMISO PET/CT to derive hypoxic volumes (HV). Patients with tumour hypoxia were randomized into standard radiochemotherapy (stdRT) (70Gy/35 fractions) or DE (77Gy/35 fractions) to the HV. Patients with non-hypoxic tumours were treated with stdRT. Loco-regional control (LRC) in hypoxic patients randomized to stdRT was compared to non-hypoxic patients. Feasibility and toxicity were analysed for patients in the DE arm and compared to stdRT. RESULTS: With a mean follow-up of 27months, LRC in hypoxic patients receiving stdRT (n=10) was significantly worse compared to the non-hypoxic group (n=5) (2y-LRC 44.4% versus 100%, p=0.048). The respective LRC for the DE group (n=10) was 70.0%. Treatment compliance as well as acute and late toxicity did not show significant differences between the DE and the standard dose arms. CONCLUSION: Tumour hypoxia determined by baseline dynFMISO PET/CT is associated with a high risk of local failure in patients with LASCCHN. First data suggest that DE to HV is feasible without excess toxicity.

SDF-1/CXCR4 expression in head and neck cancer and outcome after postoperative radiochemotherapy.

INTRODUCTION: Outcome after postoperative radiochemotherapy (RT-CT) for patients with advanced head and neck squamous cell carcinomas (HNSCC) remains unsatisfactory, especially among those with HPV negative tumours. Therefore, new biomarkers are needed to further define subgroups for individualised therapeutic approaches. Preclinical and first clinical observations showed that the chemokine receptor CXCR4 and its ligand SDF-1 (CXCL12) play an important role in tumour cell proliferation, survival, cancer progression, metastasis and treatment resistance. However, the data on the prognostic value of SDF-1/CXCR4 expression for HNSCC are conflicting. The aim of our hypothesis-generating study was to retrospectively explore the prognostic potential of SDF-1/CXCR4 in a well-defined cohort of HNSCC patients collected within the multicenter biomarker study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG). MATERIAL AND METHODS: Patients with stage III and IVA HNSCC of the oral cavity, oropharynx and hypopharynx were treated with resection and adjuvant radiotherapy (RT) with ≥60 Gy and concurrent cisplatin-based chemotherapy (CT). Tissue micro-arrays (TMAs) from a total of 221 patients were generated from surgical specimens, 201 evaluated for the SDF-1 and CXCR4 expression by immunofluorescence and correlated with clinico-pathological and outcome data. RESULTS: In univariate and multivariate analyses intracellular SDF-1 expression was associated with lower loco-regional control (LRC) in the entire patient group as well as in the HPV16 DNA negative subgroup. CXCR4 expression showed a trend for lower LRC in the univariate analysis which was not confirmed in the multivariate analysis. Neither for SDF-1 nor CXCR4 expression associations with distant metastasis free or overall survival were found. CONCLUSIONS: Our exploratory data support the hypothesis that overexpression of intracellular SDF-1 is an independent negative prognostic biomarker for LRC after postoperative RT-CT in high-risk HNSCC. Prospective validation is warranted and further exploration of SDF-1/CXCR4 as a potential therapeutic target to overcome treatment resistance in HNSCC appears promising.

Robustness of quantitative hypoxia PET image analysis for predicting local tumor control.

BACKGROUND: Previous studies suggested the maximum tumor to background ratio (TBRmax) in FMISO PET images as a potentially predictive parameter for local control after radio-chemotherapy (CRT) in head and neck squamous cell carcinomas (HNSCC). However, different TBRmax thresholds for stratification were reported, implying that a common threshold cannot readily be used among different institutions without the risk of reducing prediction accuracy. Therefore, this study investigated the robustness of using a common pre-defined TBRmax, simulating a multicenter clinical trial. MATERIAL AND METHODS: FMISO PET/CT was performed four hours post-injection in 22 patients with advanced HNSCC in a phase II FMISO dose escalation study. PET background regions of interest (ROIs) were manually defined in deep neck muscles. TBRmax was calculated as the mean of the highest-valued voxels within the high risk RT planning target volume. Its predictive power with respect to local control was tested, classifying patients using median TBRmax as threshold. The influence of systematically varying quantification between institutions was studied in silico by applying offsets of ± 10% and ± 20% to the TBRmax of all patients, while the threshold remained constant. The effect was analyzed using a receiver operating characteristic (ROC). True positive and false positive rates (TPR/FPR) as well as positive and negative predictive values (PPV/NPV) were evaluated. RESULTS: For the reference condition without an offset the median TBRmax was 2.0 (1.4-3.5). Patients were classified using this threshold and TPR = 0.7, FPR = 0.4, PPV = 0.5 and NPV = 0.8 were observed. Accuracy declined with increasing offsets. Negative offsets of -10% and -20% resulted in TPR = 0.43 and 0.14, FPR = 0.20 and 0.13, PPV = 0.50 and 0.33 and NPV = 0.75 and 0.68, respectively. Positive offsets of + 10% and + 20% resulted in TPR = 1.00 and 1.00, FPR = 0.53 and 0.67, PPV = 0.47 and 0.41 and NPV = 1.00 and 1.00, respectively. CONCLUSIONS: Using a common pre-defined TBRmax threshold in multicenter trials requires careful standardization and harmonization of all steps from patient preparation to image analysis. Our results indicate that TBRmax should deviate less than 10% from reference conditions (absolute value in this dataset ± 0.2). This conclusion likely applies to all low contrast nitroimidazole hypoxia PET tracers.

Impact of tumour volume on prediction of progression-free survival in sinonasal cancer.

BACKGROUND: The present study aimed to analyse potential prognostic factors, with emphasis on tumour volume, in determining progression free survival (PFS) for malignancies of the nasal cavity and the paranasal sinuses. PATIENTS AND METHODS: Retrospective analysis of 106 patients with primary sinonasal malignancies treated and followed-up between March 2006 and October 2012. Possible predictive parameters for PFS were entered into univariate and multivariate Cox regression analysis. Kaplan-Meier curve analysis included age, sex, baseline tumour volume (based on MR imaging), histology type, TNM stage and prognostic groups according to the American Joint Committee on Cancer (AJCC) classification. Receiver operating characteristic (ROC) curve analysis concerning the predictive value of tumour volume for recurrence was also conducted. RESULTS: The main histological subgroup consisted of epithelial tumours (77%). The majority of the patients (68%) showed advanced tumour burden (AJCC stage III-IV). Lymph node involvement was present in 18 cases. The mean tumour volume was 26.6 ± 21.2 cm(3). The median PFS for all patients was 24.9 months (range: 2.5-84.5 months). The ROC curve analysis for the tumour volume showed 58.1% sensitivity and 75.4% specificity for predicting recurrence. Tumour volume, AJCC staging, T- and N- stage were significant predictors in the univariate analysis. Positive lymph node status and tumour volume remained significant and independent predictors in the multivariate analysis. CONCLUSIONS: Radiological tumour volume proofed to be a statistically reliable predictor of PFS. In the multivariate analysis, T-, N- and overall AJCC staging did not show significant prognostic value.

A case of recurrent respiratory papillomatosis with malignant transformation, HPV11 DNAemia, high L1 antibody titre and a fatal papillary endocardial lesion.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a rare disease, which is characterised by the growth of papillomavirus-induced papillomas within the respiratory tract. Malignant transformation occurs in less than 1% of the cases. CASE PRESENTATION: We report a case of human papillomavirus (HPV) type 11-associated juvenile-onset RRP (JORRP) initially diagnosed at the age of two years. Remarkably high copy numbers of HPV11 DNA and antibody titres targeting the capsid protein L1 were detected in the patient's serum. The patient developed squamous cell carcinomas in both lungs and extraordinarily an HPV11 DNA-positive papillary endocardial lesion in the left atrium of the heart, which caused thromboembolic events leading to the patient's death at 19 years old. CONCLUSION: We here report a severe case of JORRP hallmarked by HPV11 DNAemia and very high antibody titres directed against the major viral capsid protein L1. Furthermore, the extent of malignant transformation and the discovery of a very rare fatal endocardial lesion highlight the unpredictability of JORRP and the complexity of its clinical management.

Cervical squamous cell lymph node metastases from an unknown primary site: survival and patterns of recurrence after radiotherapy.

INTRODUCTION: The purpose of the present retrospective study was to review outcome and patterns of failure of patients who were treated with radiotherapy for cervical lymph node metastases from an unknown primary site (CUP). PATIENTS AND METHODS: Between 2000 and 2009, 34 patients diagnosed with squamous cell CUP were admitted to radiotherapy in curative intent. In 26 of 34 patients (76%) neck dissection was performed prior to radiotherapy, extracapsular extension (ECE) was seen in 20 of 34 patients (59%). Target volumes included the bilateral neck and panpharyngeal mucosa. Concomitant chemotherapy was applied in 14 of 34 patients (41%). RESULTS: After a median follow-up of 45 months for the entire group, 2 of 34 patients (6%) presented with an isolated regional recurrence, another 2 of 34 patients (6%) developed both local and distant recurrence, and 6 of 34 patients (18%) had distant failure only. Estimated overall survival after 2- and 5 -years was 78% and 63%. All patients with N1 or N2a disease (n=6) were disease free after 5 years. ECE, concomitant chemotherapy and involvement of neck levels 4 and 5 were associated with worse overall survival on univariate analysis. CONCLUSION: Radiotherapy of the panpharynx and bilateral neck leads to excellent local control while distant metastases are the most frequent site of failure and prognostically limiting. Therefore intensified concomitant or sequential systemic therapies should be evaluated in future trials.

Impact of genotype and mutation type on health-related quality of life in patients with hereditary hemorrhagic telangiectasia.

CONCLUSIONS: Patients with hereditary hemorrhagic telangiectasia genotype ALK-1 (HHT2-ALK-1) with nonsense mutation demonstrated tendentially higher health-related quality of life (HR-QOL) scores than patients with HHT with genotype ENG (HHT1-ENG) with missense mutation. OBJECTIVE: HHT, also known as Osler-Weber-Rendu syndrome, comprises different expressions depending on genetic type and mutation type. The influence of HHT type on HR-QOL has not been established and is addressed in this paper. PATIENTS AND METHODS: A total of 94 patients with confirmed diagnoses of HHT (Curaçao criteria) participated in this study. EDTA (ethylene diamine tetraacetic acid) blood samples of 24 patients were sequenced genetically into genotype HHT1 (ENG) vs HHT2 (ALK-1) and mutation type missense vs nonsense. HR-QOL was assessed with the German Short Form 36 Health Survey (SF-36). RESULTS: HHT2 patients (genotype ALK-1) demonstrated significantly higher physical component scores than HHT1 patients (effect size d=0.62). Patients with genotype ENG (HHT1) with nonsense mutations showed significantly higher mental component scores than patients with missense mutations (effect size=0.79).

Quality of life after unilateral acoustic neuroma surgery via middle cranial fossa approach.

CONCLUSIONS: Patients with acoustic neuroma experienced reduced quality of life (QOL) after surgery. Individual factors did not have a significant effect on QOL. In the future, QOL should be a basic factor in the outcome evaluation of different therapeutic regimens in the treatment of acoustic neuroma. OBJECTIVE: To measure the QOL of patients who underwent unilateral acoustic neuroma surgery via the middle cranial fossa approach. MATERIAL AND METHODS: The Short Form-36 (SF-36) Health Survey and a self-designed disease-specific questionnaire were used during follow-up examinations to assess health-related QOL. The pure-tone average was used to specify hearing ability. Facial nerve function was described using the House-Brackmann grading system. A total of 28 male and 14 female patients who underwent surgery between 1997 and 2001 were included in the study. RESULTS: Patients' QOL scores revealed significant reductions in QOL in comparison to normative German QOL data. Gender, age, tumor size or location and clinical symptoms such as hearing loss and restricted facial nerve function did not have an effect on QOL. The SF-36 scales physical functioning, role functioning-physical, bodily pain, general health, social functioning and role functioning-emotional demonstrated significant QOL reductions.

How safe is percutaneous ethanol injection for treatment of thyroid nodule? Report of a case of severe toxic necrosis of the larynx and adjacent skin.

OBJECTIVE: Since 1990, percutaneous ethanol injection therapy (PEIT) has been clinically applied as a treatment for autonomous functioning nodules of the thyroid as well as for cystic lesions. Some additional indications are currently under consideration, e.g. inoperable advanced cancer of the thyroid. Since its inception, PEIT has generally been regarded as an effective, low-risk, inexpensive procedure which can be performed on an ambulatory basis. MATERIAL AND METHODS: We report the first case of severe ethyl toxic necrosis of the larynx combined with necrotic dermatitis in a patient treated with PEIT by a radiologist. RESULTS: The patient was admitted to hospital, where the necrosis and dermatitis were treated conservatively. A cyst which developed in the right false vocal fold was removed by microsurgery 10 months later. Voice was restored almost to normal but a significant reduction in nodular volume was not seen, probably due to the inexperience of the operator. CONCLUSION: PEIT for functional thyroid gland autonomy is an inexpensive method of treating hyperthyroidism with focal autonomy on an ambulatory basis if surgical intervention and radioiodine therapy are not feasible either for medical reasons or because of refusal by the patient. Severe complications must be taken into consideration and discussed with the patient. To avoid complications, substantial experience and a precise ultrasound-guided injection are required. In the case of complications the opinion of a specialist should be sought at anearly stage.