Locally-advanced head and neck squamous cell carcinoma (HNSCC) is mainly defined by the presence of pathologic cervical lymph nodes (LNs) with or without extracapsular spread (ECS). Current radiologic criteria to classify LNs as non-pathologic, pathologic, or pathologic with ECS are primarily shape-based. However, significantly more quantitative information is contained within imaging modalities. This quantitative information could be exploited for classification of LNs in patients with locally-advanced HNSCC by means of artificial intelligence (AI). Currently, various reviews exploring the role of AI in HNSCC are available. However, reviews specifically addressing the current role of AI to classify LN in HNSCC-patients are sparse. The present work systematically reviews original articles that specifically explore the role of AI to classify LNs in locally-advanced HNSCC applying Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and the Study Quality Assessment Tool of National Institute of Health (NIH). Between 2001 and 2022, out of 69 studies a total of 13 retrospective, mainly monocentric, studies were identified. The majority of the studies included patients with oropharyngeal and oral cavity (9 and 7 of 13 studies, respectively) HNSCC. Histopathologic findings were defined as reference in 9 of 13 studies. Machine learning was applied in 13 studies, 9 of them applying deep learning. The mean number of included patients was 75 (SD ± 72; range 10–258) and of LNs was 340 (SD ± 268; range 21–791). The mean diagnostic accuracy for the training sets was 86% (SD ± 14%; range: 43–99%) and for testing sets 86% (SD ± 5%; range 76–92%). Consequently, all of the identified studies concluded AI to be a potentially promising diagnostic support tool for LN-classification in HNSCC. However, adequately powered, prospective, and randomized control trials are urgently required to further assess AI’s role in LN-classification in locally-advanced HNSCC.

Many patients with head-and-neck cancer (HNC) suffer from speech or swallowing disorders. We investigated the impact of dysphagia on health-related quality of life (HRQOL), functioning, and distress in HNC survivors, and whether cancer rehabilitation can alleviate these conditions. Before admission (T0) and at discharge (T1) of three-week inpatient cancer rehabilitation, patient-reported outcomes were collected. HRQOL, symptoms, functioning, and psychological distress were assessed with EORTC QLQ-C30 and Hospital Anxiety and Depression Scale (HADS) questionnaires. Of 63 HNC patients, 22 had dysphagia, 23 needed no speech therapy (Control-1), and 18 needed speech therapy, but showed no symptoms of dysphagia (Control-2). Before rehabilitation, HRQOL, physical, social, and emotional functioning were significantly lower in dysphagia patients than in controls. Dysphagia patients reported more severe general symptoms including fatigue, pain, sleep disturbances, nausea/vomiting, diarrhea, and financial worries. Furthermore, the emotional and social functioning of Control-2 was significantly worse than Control-1. For all HNC patients, social, emotional, and role functioning, fatigue, nausea/vomiting, insomnia, and appetite loss significantly improved at T1. Improvements in HRQOL were most noticeable in dysphagia patients. Psychooncological counseling reduced depression in dysphagia and Control-2 patients to levels seen in the general population. In conclusion, dysphagia patients suffer severely from impaired functioning and systemic symptoms but benefit substantially from rehabilitation.

Background: Routine electronic assessment of patient-reported outcomes (ePROs) can improve cancer care; yet, its implementation in routine practice and long-term sustainability remain unclear. Understanding these aspects is critical to advancing the field. Objective: To review and describe the past and current status, time trends, and long-term sustainability of clinical ePRO applications in routine oncology care. Methods: We conducted a systematic review of publications on ePRO use in oncology care up to December 31, 2023, searching PubMed and Web of Science and extracting data on clinical ePRO applications. We included peer-reviewed studies including patients with cancer using ePRO assessments in clinical practice, excluding research letters and conference abstracts. Data from the review were analyzed using descriptive statistics and univariate regression models to evaluate time trends, with year of publication as the predictor. A follow-up survey was sent to authors of published ePRO applications to assess their current use of the application or reasons for discontinuation. Responses from the follow-up survey were analyzed descriptively. Results: For the review, we screened 2933 references, and 303 met inclusion criteria. Results showed that Europe was the most common region (n=141, 46.5%), and study populations consisted mostly of adult patients (n=276, 91.1%) under chemotherapy treatment (n=124, 40.9%) assessed in an outpatient setting (n=261, 86.1%). The EORTC (European Organisation for Research and Treatment of Cancer; n=77, 25.4%) and PRO-CTCAE (Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events) questionnaires (n=65, 21.5%) were most frequently integrated into ePRO applications. In the univariate analysis, we found that publications increased significantly over time (2003-2023, P<.001). Trends showed a rise in mobile app use (odds ratio [OR] 1.211, P<.001), remote assessments (OR 1.094, P=.002), and feedback provided to patients (OR 1.060, P=.04). Of the 303 studies, 221 unique clinical ePRO applications were identified, merging publications at the application level. The follow-up survey had a 35.3% response rate (78/221), with 61.1% of ePRO applications still in use, lasting a median of 5 years. The most common reason for discontinuation was a lack of funding and resources (42.9%, 12/28). Conclusions: The field of ePRO assessment in oncology is rapidly evolving, with a shift toward remote, app-based tools and a growing emphasis on providing feedback to patients. We present, for the first time, data on the sustainability of ePRO use in routine care. While our findings offer valuable insights, they should be interpreted in light of potential response bias in the follow-up survey. Several ePRO applications remain in active use, highlighting potential for long-term integration into clinical practice. However, financial constraints, limited reimbursement models, and challenges with workflow integration continue to hinder broader and more sustainable adoption. Addressing these barriers will be essential to support the continued use of ePROs in clinical care.

Current literature regarding survival and treatment outcome of SBRT in patients with pulmonary oligometastatic head and neck squamous cell carcinoma (HNSCC) is limited. Additionally, most of the published studies include metastatic lesions deriving also from primaries with histologies other than SCC when investigating the outcome of SBRT. The aim of the present retrospective study is to explore local control (LC) of treated metastases, progression-free survival (PFS), and overall survival (OS) of exclusively pulmonary oligometastatic HNSCC-patients treated with SBRT. Between 2006 and 2021, a total of 46 patients were treated with SBRT for a maximum of four pulmonary oligometastases (PM) concurrently (mean PM per patient = 2.0; range 1 to 6 PM, total of 92). Of these, 17 patients (37.0%) developed new pulmonary metastases after their first SBRT. Repeated courses of SBRT were required once in 15 patients (88.2%) and twice in 2 patients (11.8%). Median follow-up was 17 months (range, 0–109 months). One year after completion of SBRT, LC rate, PFS, and OS were 98.7%, 37.9%, and 79.5%, respectively. After two years, LC rate, PFS, and OS were 98.7%, 28.7%, and 54.9%; as well as 98.7%, 16.7%, and 31.0% after five years. Radiochemotherapy (HR 2.72, p < 0.001) or radiotherapy as primary treatment (HR 8.60; p = 0.003), as well as reduced patient performance status (HR 48.30, p = 0.002), were associated with lower PFS. Inferior OS correlated with poor performance status (HR 198.51, p < 0.001) and surgery followed by radiochemotherapy (HR 4.18, p = 0.032) as primary treatment, as well as radiotherapy alone (HR 7.11, p = 0.020). Treatment of more than one PM is an independent predictor of impaired OS (HR 3.30, p = 0.016). SBRT of HNSCC-derived PMs results in excellent LC rates and encouraging OS rates of 54.9% at two years along with good tolerability (no more than grade 2 toxicities). Favourable outcome and low toxicity also apply to repeated courses of SBRT of newly emerging PMs.

This study aims to evaluate the clinical outcome of stereotactic radiosurgery as the sole treatment for brain metastases and to assess prognostic factors influencing survival. A total of 108 consecutive patients with 213 metastases were retrospectively analyzed. Treatment was determined with close-meshed MRI follow-up. Various prognostic factors were assessed, and several prognostic indices were compared regarding their reliability to estimate overall survival. Median overall survival was 15 months; one-year overall survival was 50.5%. Both one- and two-year local controls were 90.9%. The rate of new metastases after SRS was 49.1%. Multivariate analysis of prognostic factors revealed that the presence of extracranial metastases, male sex, lower KPI, and progressive extracranial disease were significant risk factors for decreased survival. Of all evaluated prognostic indices, the Basic Score for Brain Metastases (BSBMs) showed the best correlation with overall survival. A substantial survival advantage was found for female patients after SRS when compared to male patients (18 versus 9 months, p = 0.003). SRS of brain metastasis is a safe and effective treatment option when frequent monitoring for new metastases with MRI is performed. Common prognostic scores lack reliable estimation of survival times. Female sex should be considered as an additional independent positive prognostic factor influencing survival.

Background: The crosstalk between cancer-associated fibroblasts (CAFs) and tumor cells promotes proliferation, tumor relapse, and the acquisition of a partial epithelial-to-mesenchymal (pEMT) phenotype in tumor cells. The aim of this study was to investigate the effects of patient-derived CAFs on tumor cell growth and radioresistance in head and neck squamous cell carcinoma (HNSCC). Methods: CAFs were isolated and cultured in a three-dimensional spheroid formation. SCC-25 tumor cells educated by the CAFs (SCC25-E cells) were subjected to irradiation, and the response of the CAF-stimulated tumor cells to radiotherapy was determined using an MTT assay, a clonogenic assay, and Western blotting. Tumor cell morphological changes and growth dynamics were assessed using 3D holotomographic microscopy and a live video microscope. Results: Patient-derived CAFs significantly increased the growth rate of SCC-25 cells. CAFs drove fibrosis in the tumor microenvironment (TME), functioned as a physical barrier, temporarily stopped tumor growth, and induced the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Viability after irradiation at 4–8 Gy was significantly higher in SCC25-E cells than in the controls (p = 8 × 10^–4 or lower). Furthermore, irradiation triggered the pEMT profile in HNSCC cells. Conclusions: CAFs’ education of tumor cells and the induced p38 phosphorylation had no influence on irradiation sensitivity. SCC25-E cultures demonstrated increased tumor cell growth, viability, and stress-induced phospho-p38 activation.