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Simple Summary: Many head and neck cancer patients suffer from recurrence of the tumor after previous treatment. The initial treatment usually entails operation, radiation treatment, chemotherapy, or combinations of these treatments. For those patients who have no distant metastases, there are limited options of curative treatments. Usually, surgery would be the treatment of choice. However, not all patients are operable, and the treatment results are not satisfactory. Interventional high-dose-rate radiotherapy (HDR-IRT, brachytherapy) is a special method of radiotherapy with unique physical properties. Re-irradiation with HDR-IRT combined with surgery improves the outcome and offers the patients a second chance of curative treatment. After three years of the treatment, 88% of the patients had no local recurrences. A minority of patients, approximately 35%, experienced significant yet controllable complications throughout the follow-up duration. We have confidence that this perioperative and multidisciplinary approach yields favorable clinical results with a tolerable incidence of side effects. (1) Background: to report on the use of high-dose-rate (HDR) interventional radiotherapy (brachytherapy, IRT) as a salvage treatment for patients with regionally relapsed head and neck cancers. (2) Methods: A retrospective study of 60 patients treated with HDR-IRT for loco-regionally relapsed head and neck cancers at our institution (2016–2020). Treatment procedure, results, and related toxicities were collected. Local and overall survival outcomes were analyzed. (3) Results: The median follow-up was 22.4 months. Twenty-nine (48.3%) patients had locoregional recurrences with a median time of 28.9 months. The local-recurrence free-survival was 88.1% and 37.3% at 3 years and 5 years. At the last follow-up, 21 patients were alive and the median time to death was 24 months. The overall survival was 39.2% and 16.6% at 3 years and 5 years. Collectively, there were 28 events of grade ≥ 3 late toxicities recorded in 21 patients (35%). (4) Conclusions: Salvage HDR-IRT combined with surgery offers a second-line curative treatment option for regionally relapsed head and neck cancers with acceptable outcomes and toxicities. [ABSTRACT FROM AUTHOR]

Many head and neck cancer patients assigned to definitive or adjuvant chemoradiation treatment do not complete the concurrent cisplatin dose. We determined corresponding risk factors and developed a prognostic instrument to help identify these patients. Ten pre-treatment characteristics were retrospectively analyzed in 154 patients with head and neck cancer who were treated via chemoradiation with cisplatin. These pre-treatment characteristics included age, sex, Karnofsky performance score, tumor site, primary tumor stage, nodal stage, histologic grade, upfront surgery, human papilloma virus status, and history of smoking. The characteristics significantly associated with the completion of cisplatin-based treatment, the receipt of ≥80% cisplatin, or showing a strong trend of association after multivariate analyses were used for the prognostic instrument. For each characteristic, 0 points were assigned for worse outcomes, and 1 point was assigned for better outcomes. Patients' scores were calculated by adding these points. Age ≤ 60 years and a Karnofsky performance score of 90–100 were significantly associated with both endpoints after multivariate analysis, and male gender showed a trend for association with the receipt of ≥80% cisplatin. Patient scores were 0, 1, 2, and 3 points. The corresponding rates of completion of cisplatin-based treatment were 14%, 41%, 62%, and 72%, respectively (p = 0.004). The rates of receipt of ≥80% cisplatin were 29%, 54%, 72%, and 94%, respectively (p < 0.001). This new prognostic instrument helps to predict whether head and neck cancer patients scheduled for chemoradiation will receive cisplatin as planned. [ABSTRACT FROM AUTHOR]

Many patients with squamous cell carcinoma of the head and neck (SCCHN) receive cisplatin-based chemoradiation. Cisplatin 100 mg/m2 every three weeks is toxic and alternative cisplatin regimens are desired. Two courses of 20 mg/m2/day 1–5 (cumulative 200 mg/m2) were shown to be similarly effective and better tolerated than 100 mg/m2 every three weeks. Previous studies suggested that cumulative doses >200 mg/m2 may further improve outcomes. In this study, 10 patients (group A) receiving two courses of 25 mg/m2/day 1–5 (cumulative 250 mg/m2) in 2022 were retrospectively matched and compared to 98 patients (group B) receiving two courses of 20 mg/m2/day 1–5 or 25 mg/m2/day 1–4 (cumulative 200 mg/m2). Follow-up was limited to 12 months to avoid bias. Group A achieved non-significantly better 12-month loco-regional control (100% vs. 83%, p = 0.27) and metastases-free survival (100% vs. 88%, p = 0.38), and similar overall survival (89% vs. 88%, p = 0.90). No significant differences were found regarding toxicities, completion of chemotherapy, and interruption of radiotherapy. Given the limitations of this study, chemoradiation with two courses of 25 mg/m2/day 1–5 appears an option for carefully selected patients as a personalized treatment approach. Longer follow-up and a larger sample size are needed to properly define its role. [ABSTRACT FROM AUTHOR]

Simple Summary: Bruton's Tyrosine Kinase (BTK) was originally considered to be primarily expressed in cells of hematopoietic origin. Apart from the 77 kDa BTK isoform expressed in immune cells, elevated expression of novel BTK isoforms of 80 and 65 kDa have been recently described for several solid tumor entities. These newly described isoforms have been linked to tumor growth and poor prognosis. Therefore, we aimed to investigate whether BTK isoforms are also expressed in head and neck squamous cell carcinoma (HNSCC) and further the molecular and cellular consequences of BTK expression for HNSCC tumorigenesis. We confirmed the expression of the BTK-p65 and BTK-p80 isoforms in HNSCC and revealed that both isoforms are products of the same mRNA. Abrogation of BTK activity inhibited tumor progression in our study. Thus, targeting BTK activity appears as a promising therapeutic option for patients suffering from BTK expressing HNSCC. Here, we describe the expression of Bruton's Tyrosine Kinase (BTK) in head and neck squamous cell carcinoma (HNSCC) cell lines as well as in primary HNSCC samples. BTK is a kinase initially thought to be expressed exclusively in cells of hematopoietic origin. Apart from the 77 kDa BTK isoform expressed in immune cells, particularly in B cells, we identified the 80 kDa and 65 kDa BTK isoforms in HNSCC, recently described as oncogenic. Importantly, we revealed that both isoforms are products of the same mRNA. By investigating the mechanism regulating oncogenic BTK-p80/p65 expression in HNSSC versus healthy or benign tissues, our data suggests that the epigenetic process of methylation might be responsible for the initiation of BTK-p80/p65 expression in HNSCC. Our findings demonstrate that chemical or genetic abrogation of BTK activity leads to inhibition of tumor progression in terms of proliferation and vascularization in vitro and in vivo. These observations were associated with cell cycle arrest and increased apoptosis and autophagy. Together, these data indicate BTK-p80 and BTK-p65 as novel HNSCC-associated oncogenes. Owing to the fact that abundant BTK expression is a characteristic feature of primary and metastatic HNSCC, targeting BTK activity appears as a promising therapeutic option for HNSCC patients. [ABSTRACT FROM AUTHOR]

Background: Patients with human papilloma virus (HPV)-related oropharyngeal cancer have a better prognosis than nonvirally associated patients, most likely because of better immune responses. Increased infiltration of T lymphocytes into the oropharyngeal tumor tissue has been observed, but the dynamics of circulating lymphocytes and monocytes are not fully understood. The aim of this study was to understand the population dynamics of circulating monocyte subsets in oropharyngeal cancer (OPC) patients with regard to the clinicopathological parameters and accompanying immunological consequences in view of the CD4/CD8 T cell subset composition, and the expression of checkpoint pathway proteins programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1). Materials and Methods: The abundance of circulating monocyte subsets and peripheral blood CD4/CD8 T cells of oropharyngeal cancer patients and their PD-L1 and PD-1 expression levels were analyzed by flow cytometry. Results: The studied oropharyngeal cancer patients revealed heterogeneous individual redistributions of CD14++CD16− (classical), CD14++CD16+ (intermediate), and CD14dim+CD16+ (nonclassical) monocyte subsets compared with healthy donors. These differences in monocyte subset alterations were independent in patients with TNM or HPV status but entailed further immunological consequences. Increased percentages of nonclassical monocytes significantly correlated with increased levels of monocytic PD-L1 expression. We observed significantly decreased levels of CD4+ effector T cells, which were accompanied by increased CD4+ effector memory T cells in OPC patients compared with healthy donors, each having a stronger effect in patients with decreased levels of classical monocytes. Conclusion: We conclude that oropharyngeal cancer, as a malignancy from a lymphoid-tissue-rich anatomical region, has a strong systemic impact on the differentiation and regulation of circulating innate and adaptive immune cells. Further comprehensive investigations are required for the possible future usability of the described immunological alterations as bioliquid parameters for prognosis or therapy response prediction. [ABSTRACT FROM AUTHOR]

Simple Summary: The formation of head and neck squamous cell carcinoma (HNSCC) is closely associated with cigarette smoking, alcohol abuse, and aging, but the immunologic alterations of peripheral monocytes and T-cells within this process are not fully understood. We aimed to investigate the impact of these factors on the abundances and characteristics of monocytes and CD4/CD8 T-cell subsets in the peripheral blood. Our data revealed distinct impacts of the individual behavior and age on the dynamics of these circulating immune cell subsets in head and neck cancer patients. Head and neck squamous cell carcinoma (HNSCC) represents a heterogeneous malignant disease of the oral cavity, pharynx, and larynx. Although cigarette smoking, alcohol abuse, and aging are well-established associated factors for HNSCC, their respective influence on immunologic alterations of monocyte subsets or T-cell compositions in the peripheral blood has not yet been fully unveiled. Using flow cytometry, whole blood measurements of CD14/CD16 monocyte subsets and analyses of T-cell subsets in isolated PBMC fractions were carried out in 64 HNSCC patients in view of their tobacco and alcohol consumption, as well as their age, in comparison to healthy volunteers. Flow cytometric analysis revealed significantly increased expression of monocytic CD11b, as well as significantly decreased expression levels of CX3CR1 on classical and intermediate monocyte subsets in smoking-related and in alcohol-related HNSCC patients compared to healthy donors. Peripheral monocytes revealed an age-correlated significant decrease in PD-L1 within the entirety of the HNSCC cohort. Furthermore, we observed significantly decreased abundances of CD8+ effector memory T cells in active-smoking HNSCC patients and significantly increased percentages of CD8+ effector T cells in alcohol-abusing patients compared to the non-smoking/non-drinking patient cohort. Our data indicate an enhanced influence of smoking and alcohol abuse on the dynamics and characteristics of circulating monocyte subsets and CD4/CD8 T-cell subset proportions, as well as an age-related weakened immunosuppression in head and neck cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: We detected an increase in the mean age at diagnosis among 2450 patients with head and neck carcinoma diagnosed between 2004 and 2018 in the head and neck cancer center Ulm (Germany) in comparison to the mean age in the general population of the main catchment area. Carcinoma incidences were rising too. The steepest ascent in incidence rates was found in the age group >70 years of age. These results indicate that health care providers need to prepare for an increasingly older group of cancer patients. This study is the first step to a nationwide analysis among German patients. Background: The impact of demographic change on the age at diagnosis in German head and neck cancer (HNC) patients is unclear. Here we present an evaluation of aging trends in HNC at a tertiary referral center. Methods: Retrospective cohort study on aging trends at the initial diagnosis of newly diagnosed patients with HNC between 2004 and 2018 at the head and neck cancer center Ulm in relation to demographic data of the catchment area. Results: The study population consisted of 2450 individuals diagnosed with HNC with a mean age of 62.84 (±11.67) years. We observed a significant increase in annual incidence rates and mean age over time. Mean age among HNC patients increased significantly more than among the population in the catchment area. Whereas the incidence rate of patients <50 years did not change, the incidence of HNC patients aged ≥70 years increased the most. The mean patient age in the main tumor sites increased significantly. Surprisingly, HPV-positive patients were not younger than HPV-negative patients, but showed a non-significant trend towards a higher mean age (63.0 vs. 60.7 years). Conclusions: Increasing incidence rates in older patients pose a challenge for health care systems. A nationwide study is needed to assess the dynamics and impact of aging on the incidence of HNC. [ABSTRACT FROM AUTHOR]