Tumour budding-based grading as independent prognostic biomarker in HPV-positive and HPV-negative head and neck cancer.

BACKGROUND: The prognostic significance of tumour budding (TB) and minimal cell nest size (MCNS) was shown in human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCC). However, the optimisation of cutpoints, the prognostic impact in HPV-positive HNSCC, and the comparison with other histopathological grading systems are insufficiently investigated. METHODS: TB and MCNS were analysed digitally in 1 and 10 high-power fields (HPF) of 331 HPV-positive and HPV-negative cases from TCGA. Optimising the cutpoints a new cellular dissociation grading (CDG) system was defined and compared to the WHO grading and the Brandwein-Gensler (BG) risk model. RESULTS: The two-tiered CDG system based solely on TB yielded optimal prognostic stratification with shortened overall survival for CDG-high cases. Optimal cut-offs were two buds (1 HPF) and six buds (10 HPF), respectively. Analysing MCNS did not add prognostic significance to quantifying TB. CDG was a significant prognostic marker in HPV-negative and HPV-positive tumours and prognostically superior to the WHO and BG systems. High CDG was associated with clinically occult lymph-node metastases. CONCLUSIONS: The most comprehensive study of TB in HNSCC so far confirmed its prognostic impact in HPV-negative tumours and for the first time in HPV-positive tumours. Further studies are warranted to evaluate its applicability for therapy guidance in HNSCC.

The role of psycho-oncologic screenings in the detection and evaluation of depression in head and neck cancer aftercare patients.

PURPOSE: Cancer and morbidity during a therapeutic regimen can result in somatic and psychiatric impairment. We have evaluated the need of appropriate psychological screening by analyzing a large collective of head and neck cancer (HNC) patients with particularly burdensome symptoms. METHODS: HNC-aftercare patients were asked about somatic and psychological symptoms by means of standardized questionnaires of the European Organization for Research and Treatment of Cancer (EORTC Q30 and QLQ-H&N35). Patients with poor well-being values on the World Health Organization-5-Well-Being Index were screened for depression by using the Mini International Neuropsychiatric Interview, and adequate treatment was initiated, if necessary. RESULTS: Our sample consisted of 453 HNC-aftercare patients (average age 64.5 years; 72.0% male; 28.0% female). 25.1% showed abnormalities based on their WHO-5 questionnaire. A current major depressive episode was observed in 8.5% of the total study group. Patients with lip and oral cavity tumors showed the highest depression prevalence (18.9%). Time since initial HNC diagnosis showed no clear trend with regard to the number of depression cases. 50.0% of patients with a current major depressive episode consented to receiving assistance and/or therapy. Within the total study population, the most burdensome symptoms were found to be "dry mouth" (48.3%), "trouble doing strenuous activities" (46.0%), "trouble taking a long walk" (38.5%), and "worry" (35.5%). Aftercare patients with a depression diagnosis tended to have heavier symptom burdens than people without major depression. CONCLUSIONS: Despite the various cancer-related burdensome factors, prevalence levels of depression among the HNC-aftercare patients and the general population were similar. Nevertheless, since the number of diagnosed depression cases is high, the need for psychological treatment should be considered within the tumor collective. Furthermore, screening for depression should be implemented in clinical routines by using the appropriate standardized questionnaires.

Report on Late Toxicity in Head-and-Neck Tumor Patients with Long Term Survival after Radiochemotherapy.

Regular tumor follow-up care provided by ear-nose-throat (ENT) specialists ends when patients reach 5-year survival, but radiotoxicity is a continuous lifelong process. In this study, long-term head-and-neck cancer (HNC) survivors undergoing tumor follow-up (FU) care exceeding five years in a certified HNC center of a German university hospital were analyzed for newly diagnosed late sequelae after radio-(chemo-)therapy. Patients diagnosed with squamous cell carcinoma (SCC) of the oral cavity, larynx or oro-/hypopharynx receiving treatment between 1990 and 2010 with a tumor FU care beyond five years were reviewed retrospectively for signs of late sequelae after radio-(chemo-)therapy (R(C)T) including carotid artery stenosis, stenosis of the cranial esophagus, dysphagia, osteoradionecrosis, and secondary malignancies. Long-term survivors that solely received surgical treatment served as control. Of 1143 analyzed patients we identified 407 patients with an overall survival beyond five years, 311 with R(C)T and 96 patients without R(C)T. Furthermore, 221/1143 patients were lost to FU and the mortality rate within the first 5-years was 45%. Moreover, 27.7% of the long-term survivors were diagnosed with new onset late sequelae within the following five years. RT was significantly associated with a two-fold risk increase for newly diagnosed symptoms, especially after RT of the lymphatic pathways (LP) which showed a hazard ratio of 23.3 to develop alterations on the carotid arteries. Additional chemotherapy had no statistical correlation with any late onset toxicity nor did the mode of R(C)T (adjuvant/definitive). Although the validity of this study might be limited due to its retrospective nature and the dependence on the voluntary participation in a prolonged tumor FU, the results nevertheless provide the need to offer and encourage a tumor FU by ENT specialists exceeding the common 5-year margin. This could prevent secondary morbidities and improve quality of life for long-term cancer survivors.

Radiooncological View on Therapy Outcome after Multidisciplinary Treatment of Sinonasal Tumors.

PURPOSE: We report the outcome of a mono-institutional retrospective study of sinonasal carcinoma with the primary focus on GTV (gross tumor volume) and the effect of radiotherapy. METHODS: 53 patients with sinonasal carcinoma and that of the nasal cavity, paranasal sinus or both except lymphoma were included. All patients were treated between 1999 and 2017. For tumor volume delineation, all pre-therapeutic images were fused to the planning CT (computed tomography). RESULTS: The median follow-up was 17 months [0.3-60], the median age 60 years, 35 males and 18 females were included. Squamous cell carcinoma (SCC) (60.4%) was the predominant histology, followed by adenocarcinoma (15.1%). The mean composite OS (overall survival) time was 33.3 ± 3.5 months. There was no significant difference in the 5 y composite OS between tumor localization or radiotherapy setting. The simultaneous integrated boost concept showed a trend towards improving five-year composite OS compared to the sequential boost concept. The only factor with a significant impact on the 5 y composite OS rate was the pre-therapeutic GTV (cutoff 75 cm3; p = 0.033). The GTV ≥ 100 cm3 has no effect on the 5 y composite OS rate for SCC. CONCLUSIONS: The pre-therapeutic GTV is a prognostic factor for five-year composite OS for the entire group of patients with sinonasal tumors, influencing the outcome after completion of all treatment strategies. The GTV seems to not influence five-year composite OS in SCC. For this rare tumor entity, an intensive, multidisciplinary discussion is essential to finding the best treatment option for the patient.

[GERD and adjuvant radio-chemotherapy predespose to recurrent voice prosthesis leakage]. / GERD und adjuvante Radiochemotherapie prädisponieren für rezidivierende Stimmprotheseninsuffizienz.

After total laryngectomy, regaining ability to speech is a keystone in regards of life quality. Voice prostheses have been shown to be a sufficient tool for satisfying communication, although frequent replacements of prostheses are burdening certain patients. Therefore, a more accurate understanding of mechanisms of prosthetic leakage is urgently needed. METHODS: We performed a retrospective analysis of 58 Patients after laryngectomy. Additionally, we analyzed pre- and post-therapeutic CT-scans of 22 Patients regarding pharyngeal stenosis. RESULTS: In 40 Patients, at least one replacement of voice prosthesis was documented during observation period, median device life was 235 days. Patients treated with adjuvant radiotherapy (RT) showed a significantly longer device life than patients with adjuvant radio-chemotherapy (RCT, p = 0.002). Furthermore, patients suffering of gastroesophageal reflux disease (GERD) showed a significantly shortened device life (p = 0.04).17 patients (42.5 %) suffered of clinically relevant stenosis of the neopharynx, which was treated with dilatation in 14 patients (82 %) and did not affect prosthesis device life. CONCLUSION: GERD is a risk factor for shortened voice prosthesis' device life and therefore should be treated effectively after laryngectomy. Also, adjuvant RCT predisposes a shortened device life.Stenosis is observed frequently after laryngectomy but does not affect device life when effectively treated.

Laryngeal and Pharyngeal Movements During Inner Singing: A Cross-Sectional Study.

INTRODUCTION: Laryngeal and pharyngeal activity during inner singing is discussed in the context of vocal hygiene. Inner singing is defined as imagined singing, reading music silently, and listening to vocal music. When vocal rest is prescribed, doctors, speech therapists, and voice pedagogues recommend avoiding listening to music or reading music silently, since it is suggested that inner singing unconsciously influences the glottis, and thus moves the vocal folds involuntarily. The aim of this study was to compare the degree to which involuntary laryngeal and/or pharyngeal activity occur during inner singing, inner speech, and at rest, and to evaluate if current recommendations concerning vocal hygiene are still reasonable. MATERIAL AND METHOD: Thirty vocally healthy participants were examined transnasally with a flexible videoendoscope. The sample consisted of 10 nonsingers, 10 lay singers, and 10 professional singers. Participants were examined during five tasks including rest, silent reading, imagining a melody, listening to music, and reading music. Two medical doctors specializing in phoniatrics analyzed the videos both qualitatively and quantitatively. RESULTS: During the endoscopic examination, the raters identified movements at the base of the tongue, the posterior and lateral pharynx wall, the arytenoid cartilage, and the vocal folds. The inner singing tasks showed significantly more laryngeal movements as well as significantly more glottal closures than the control tasks (at rest, silent reading). Pharyngeal structures did not show an increase in activity during inner singing. These findings were independent of the level of proficiency in singing. CONCLUSION: When total vocal rest is prescribed, patients should also be advised to avoid music imagination. Still, further research is needed to survey in detail the actual effects of these involuntary movements during inner singing on the regeneration process of vocal fold healing.

Liposarcoma of the Thyroid: A Case Report with a Review of the Literature.

BACKGROUND: Liposarcomas of the thyroid gland are extremely rare tumors, and, to our knowledge, only 12 cases have been reported in the English literature. An accurate diagnosis is challenging due to the nonspecific clinical presentation of this cancer, frequently defined just by a swelling of the neck. PATIENT FINDINGS: We present an 82-year-old woman with liposarcoma of the thyroid, complaining of a fast-growing neck mass. MRI and neck ultrasound showed a large lipomatous mass, which corresponded to a cold nodule in the thyroid scan. After performing a total thyroidectomy, the diagnosis of a well-differentiated liposarcoma of the thyroid gland was made, showing an MDM2 amplification in fluorescence in situ hybridization. Since neither a metastasis nor a residual tumor was found, no further adjuvant therapy was needed. RESULTS: We searched the literature for previous case reports and identified only 12 cases worldwide to form our database. A demographic as well as clinical and histopathological analysis was made. In most cases, the liposarcoma occurred in patients >60 years of age. All histological subtypes, such as well-differentiated and myxoid liposarcomas, and pleomorphic and dedifferentiated liposarcomas, were found in the literature. In only 38.46% of the cases, an infiltration of the adjacent organs was observed. Surgery was the most common treatment chosen. CONCLUSIONS: Our review provides clinical and histopathological features of a primary liposarcoma of the thyroid to enable the identifi-cation of this rare tumor entity and assist in the decision-making process regarding therapeutic options and tumor follow-up.

HNSCC cells resistant to EGFR pathway inhibitors are hypermutated and sensitive to DNA damaging substances.

Despite remarkable successes with targeted therapies in the treatment of cancer, resistance can occur which limits the clinical outcome. In this study, we generated and characterized resistant cell clones derived from two different head and neck squamous cell carcinoma (HNSCC) cell lines (Cal27, UD-SCC-5) by long-term exposure to five targeted- and chemotherapeutics (afatinib, MK2206, BEZ235, olaparib and cisplatin). The resistant tumor cell clones showed an increased ERK1/2 expression and an altered expression of the stem-cell markers CD44, ALDH1, Oct4, Sox2, Nanog and Bmi1. None of the single markers alone was predictive for resistance to all five targeted- and chemotherapeutics. Furthermore, long-term exposure of tumor cells to these five drugs resulted in an eightfold increase in the mutational rate compared to untreated cells. Interestingly, targeted- and chemotherapy resistant cell clones remained sensitive to irradiation. Lastly, clones that were resistant to afatinib, MK2206 or BEZ235 showed cross-resistance to further treatment with therapeutics that affect the same signaling pathway, but remained sensitive to those affecting different pathways such as cisplatin and olaparib. In contrast, cell clones which were once resistant to cisplatin or olaparib were found to be multidrug-resistant. These data might indicate that patients with HNSCC benefit more by a first line targeted therapy followed by cisplatin as a second line therapy.