Feasibility of individualized home exercise programs for patients with head and neck cancer-study protocol and first results of a multicentre single-arm intervention trial (OSHO #94).

INTRODUCTION: Patients with head and neck cancer (PwHNC) benefit from targeted exercise interventions: symptom relief, compensation for dysfunction, improvement in quality of life (QoL). Data on acceptance physical interventions in PwHNC are rare. The 'OSHO #94' trial investigates the short- and medium-term effects of individualized home exercise in PwHNC on QoL, physical activity and functionality. The study includes a feasibility phase (proof of concept) in order to evaluate the acceptance. Here we present the study protocol as well as the feasibility results. METHODS AND ANALYSIS: This prospective, multicentre, single-arm intervention study includes PwHNC ≥18 years of age in aftercare or palliative care with stable remission under immunotherapy. The study opened in January 01, 2021, with estimated completion by December 31, 2024. The PwHNC receive an individualized home exercise program consisting of mobilization, coordination, strengthening and stretching exercises. This should be carried out at least three times a week over 12 weeks for 15 to 30 minutes, supplemented by aerobic training two to three times a week for 30 minutes (intervention). Once weekly telephone calls with a physiotherapist are performed. Subsequently, there is a 12-week follow-up (FU) without exercise specifications/contact. Outcomes are measured before and after the intervention and following the FU. Primary outcome of the feasibility phase (n = 25) was the determination of the dropout rate during the intervention with a termination cut off if more than 30% PwHNC withdrew premature. The primary outcome of the OSHO #94' trial (N = 53) is the change in global QoL score from pre- to post-intervention (EORTC QLQ-C30). Secondary outcomes include clinical and patient-reported measures, training details as well as functional diagnostic data (e.g. level of physical activity, training frequency, flexibility, fall risk and aerobic performance). RESULTS: 25 PwHNC were enrolled onto the feasibility cohort. Only16% (4/25 patients) did not complete the study. Therefore, recruitment of PwHNC was continued. The dropout rate was adjusted from 30% (N = 60) to 20% (N = 53, calculated sample size n = 42 PwHNC and 20% (n = 11) to dropout). CONCLUSIONS: Individualized home exercise programs in PwHNC in aftercare seem feasible. Consequently, the aim is now to evaluate the short and medium-term effects of individualized home exercise.

Tolerability and efficacy of the cancer vaccine UV1 in patients with recurrent or metastatic PD-L1 positive head and neck squamous cell carcinoma planned for first-line treatment with pembrolizumab - the randomized phase 2 FOCUS trial.

Background: Globally, head and neck squamous cell carcinoma (HNSCC) is the seventh most common malignancy. Despite aggressive multimodal treatment approaches, recurrent and/or metastatic (R/M) disease develops in >50% of patients. In this setting, pembrolizumab was approved for patients with PD-L1 expression. However, response rates with checkpoint inhibitor monotherapy remain limited and strategies to strengthen tumor-directed immune responses are needed. Objective: The FOCUS trial is designed to estimate the effectiveness of UV1 vaccination in combination with pembrolizumab versus pembrolizumab as a single agent in patients with R/M HNSCC. Methods and analysis: The FOCUS trial is a two-armed, randomized, multicenter phase II study which was designed to evaluate the efficacy and feasibility of the hTERT-targeted cancer vaccine UV1 as add-on to pembrolizumab in the 1st line treatment of patients with R/M PD-L1 positive (combined positive score ≥1) HNSCC. Secondary objectives are the exploration of patient subgroups most likely deriving benefit from this novel combination and the establishment of liquid biopsy tumor monitoring in HNSCC. Ethics and dissemination: This clinical study was designed and will be conducted in compliance with Good Clinical Practice and in accordance with the Declaration of Helsinki. It is intended to publish the results of this study in peer-reviewed scientific journals and to present its content at academic conferences. Conclusions: A significant number of patients with R/M HNSCC are frail and may not tolerate chemotherapy, these patients may only be suitable for pembrolizumab monotherapy. However, long term disease stabilizations remain the exception and there is a need for the development of efficacious combination regimens for this patient population. The FOCUS study aims to optimize treatment of R/M HNSCC patients with this promising new treatment approach. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT05075122, identifier NCT05075122.

Prevalence of Obstructive Sleep Apnea in Head and Neck Squamous Cell Carcinoma Patients before and after Treatment.

Background and Objectives: Obstructive sleep apnea (OSA) is common not only in the general population but even more so in patients with tumors of the head and neck region. Untreated, it leads to reduced quality of life, increased daytime sleepiness, and other comorbidities. The aim of this study was to determine the difference in the occurrence of OSA in the patient population with head and neck tumors compared with the general population as represented by the Trend cohort of the Study of Health in Pomerania (SHIP), and to assess the influence of tumor treatment. Materials and Methods: Between July 2018 and December 2021, preoperative polysomnography was conducted in 47 patients with histologically confirmed squamous cell carcinoma in the oropharynx, hypopharynx, or larynx. A follow-up polysomnography was performed in 23 patients 2-11 months after completing treatment. The collected data were correlated with tumor treatment and tumor size. Results: Of the included patients, 43 were male and 4 were female. Age ranged from 54 to 90 years. The pretherapeutic measurement found no significant difference in the prevalence of a pathologically elevated apnea-hypopnea index (AHI) in our patients compared with the SHIP Trend cohort. In the follow-up measurement after completion of treartment, a significant deterioration in AHI was observed. Initially, 70% of patients had an AHI > 5; after therapy, this increased to 87% (p = 0.008). The effect was particularly pronounced in the group of patients with advanced tumor stages who had received primary chemoradiation. Conclusions: OSA is a relevant condition in patients with head and neck cancer. Tumor treatment can lead to an increased occurrence of sleep-related breathing disorders, especially in patients with advanced tumor stages undergoing primary chemoradiation. Additional studies are necessary to better understand the exact mechanism involved.

[Current trends in liquid biopsy and diagnostics-contributions from ASCO and ESMO 2022]. / Aktueller Stand zu "liquid biopsy" und Diagnostik ­ Beiträge vom ASCO und ESMO 2022.

BACKGROUND: Liquid biopsy is a promising new diagnostic tool that is already used in clinical practice for multiple tumor entities and which also has great potential for head and neck cancer. Herein, the authors discuss a selection of publications from the American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) meetings in 2022. OBJECTIVE: Relevant publications are evaluated and summarized. METHODS: Using a databank inquiry, abstracts from the 2022 ASCO and ESMO conferences regarding liquid biopsy and related diagnostics for head and neck squamous cell carcinoma were collected. Work without relevant data and statements of intent were not included. Duplicate articles across conferences were only quoted once. A total of 532 articles were screened, 50 articles were selected for further review, and 9 articles were selected for presentation. RESULTS: Six articles on cell- and RNA-based liquid biopsy and three articles on more general diagnostic tools in the treatment of head and neck cancer are presented. The results are discussed in relation to current treatment standards. CONCLUSION: Multiple studies show promising results for the use of circulating tumor DNA (ctDNA) for treatment surveillance in head and neck cancer. Integration into clinical practice will depend on larger study cohorts and sinking costs.

Population Based Average Parotid Gland Volume and Prevalence of Incidental Tumors in T1-MRI.

Representative epidemiologic data on the average volume of the parotid gland in a large population-based MRI survey is non-existent. Within the Study of Health in Pomerania (SHIP), we examined the parotid gland in 1725 non-contrast MRI-scans in T1 weighted sequence of axial layers. Thus, a reliable standard operating procedure (Intraclass Correlation Coefficient > 0.8) could be established. In this study, we found an average, single sided parotid gland volume of 27.82 cm3 (95% confidence interval (CI) 27.15 to 28.50) in male and 21.60 cm3 (95% CI 21.16 to 22.05) in female subjects. We observed positive associations for age, body mass index (BMI), as well as male sex with parotid gland size in a multivariate model. The prevalence of incidental tumors within the parotid gland regardless of dignity was 3.94% in the Northeast German population, slightly higher than assumed. Further epidemiologic investigations regarding primary salivary gland diseases are necessary.

Reliability of the Acoustic Voice Quality Index AVQI and the Acoustic Breathiness Index (ABI) when wearing CoViD-19 protective masks.

PURPOSE: Investigating whether the Acoustic Voice Quality Index (AVQI) and the Acoustic Breathiness Index (ABI) are valid and comparable to previous unmasked measurements if the speaker wears a surgical mask or a FFP-2 mask to reduce the risk of transmitting air-borne viruses such as SARS-CoV-2. METHODS: A convenience sample of 31 subjectively healthy participants was subjected to AVQI and ABI voice examination four times: Twice wearing no mask, once with a surgical mask and once with a FFP-2 mask as used regularly in our hospital. The order of the four mask conditions was randomized. The difference in the results between the two recordings without a mask was then compared to the differences between the recordings with each mask and one recording without a mask. RESULTS: Sixty-two percent of the AVQI readings without a mask represented perfectly healthy voices, the largest AVQI without a mask value was 4.0. The mean absolute difference in AVQI was 0.45 between the measurements without masks, 0.48 between no mask and surgical mask and 0.51 between no mask and FFP-2 mask. The results were neither clinically nor statistically significant. For the ABI the resulting absolute differences (in the same order) were 0.48, 0.69 and 0.56, again neither clinically nor statistically different. CONCLUSION: Based on a convenience sample of healthy or only mildly impaired voices wearing CoViD-19 protective masks does not substantially impair the results of either AVQI or ABI results.

Tissue Microarray Analyses Suggest Axl as a Predictive Biomarker in HPV-Negative Head and Neck Cancer.

The receptor tyrosine kinase Axl is described to promote migration, metastasis and resistance against molecular targeting, radiotherapy, and chemotherapy in various tumor entities, including head and neck squamous cell carcinoma (HNSCC). Since clinical data on Axl and its ligand Gas6 in HNSCC are sparse, we assessed the association of Axl and Gas6 expression with patient survival in a single center retrospective cohort in a tissue microarray format. Expression was evaluated manually using an established algorithm and correlated with clinicopathological parameters and patient survival. A number of 362 samples yielded interpretable staining, which did not correlate with T- and N-stage. Protein expression levels were not associated with the survival of patients with p16-positive oropharyngeal SCC. In HPV-negative tumors, Axl expression did not impact patients treated with primary or adjuvant radio(chemo)therapy, but was significantly associated with inferior overall and recurrence-free survival in patients treated with surgery alone. Gas6 was a positive predictor of survival in patients whose treatment included radiotherapy. Associations remained significant in multivariable analysis. Our data question a meaningful contribution of the Axl/Gas6 pathway to radio-resistance in HNSCC and instead suggest that strong Axl expression identifies tumors requiring adjuvant radio(chemo)therapy after surgery.

[Chemotherapy and targeted therapy of head and neck squamous cell carcinomas at the 2021 ASCO meeting]. / Chemotherapie und zielgerichtete Therapie von Kopf-Hals-Plattenepithelkarzinomen beim ASCO-Kongress 2021.

BACKGROUND: This article summarizes new findings on chemo- and targeted therapy of head and neck squamous cell carcinoma presented at the 2021 American Society of Clinical Oncology (ASCO) conference. OBJECTIVE: Relevant publications were evaluated and summarized. METHODS: The abstract database of the 2021 ASCO conference was searched. Publications were selected if they focused on chemo- or targeted therapies in head and neck squamous cell carcinoma. Publications covered in other articles of this issue were omitted, as were study proposals without results. RESULTS: The authors present six articles. Dosage and novel forms of application are shown for cisplatin. Cetuximab is used in the neoadjuvant setting and for progressive disease following immune therapy. Lastly, two new drugs in the form of liposomal irinotecan and the mHRAS inhibitor tipifarnib are discussed. CONCLUSION: Patient-specific and possibly local application of cisplatin might be considered in the future. Moreover, mHRAS inhibition might also be useful for selected patients after sequencing.

Design-Dependent Calculation of the Prosthesis Length in Malleostapedotomy.

OBJECTIVE: The results of a recently published micro-CT study suggested a correlation of the distance between long incus process and stapes footplate and the required prosthesis length in malleostapedotomy. The goal of this study was to test the reliability of that assumption. METHODS: Rectangular and bent prostheses were tested in 11 cadaveric human temporal bone specimens; 1 of them showed a stapedial artery. Prosthesis length was calculated based on the distance between long incus process and stapes footplate. The rate of acceptable prosthesis insertion into the vestibule was investigated. RESULTS: In both prostheses designs, the insertion depth into the vestibule did not exceed 1.0 mm. Two prostheses did not pass the footplate level in bent prostheses (18%) and 1 in rectangular prostheses (9%). CONCLUSION: A rough estimation of the required prosthesis length in malleostapedotomy seems possible if the distance between long incus process and stapes footplate is known and a design-dependent equation exists.