Head and Neck Cancer: A Study on the Complex Relationship between QoL and Swallowing Function.

Head and neck squamous cell carcinoma (HNSCC) is linked to significant morbidity, adversely affecting survival and functional capacity. Post-treatment challenges such as pain, dysphonia, and dysphagia are common, prompting increased attention in survivorship research. Quality of Life (QoL) questionnaires, especially the MD Anderson Dysphagia Inventory (MDADI), are prevalent outcome measures in clinical studies but often lack parallel objective swallowing function evaluations, leading to potential outcome discrepancies. This study aimed to illuminate the relationship between subjective QoL (EQ-5D-5L and MDADI) measures and objective swallowing function (evaluated via Fiberoptic Endoscopic Evaluation of Swallowing, FEES) in patients with HNSCC. The analysis revealed a notable discordance between objective measures of swallowing function, such as the Penetration-Aspiration Scale (PAS) and residue ratings in the vallecula or piriform sinus, and patients' subjective QoL assessments (p = 0.21). Despite the lack of correlation, swallowing-related QoL, as measured by the MDADI, was more indicative of disease severity than generic QoL assessments. Generic QoL scores did not demonstrate substantial variation between patients. In contrast, MDADI scores significantly declined with advancing tumor stage, multimodal therapy, and reliance on feeding tubes. However, the clinical significance of this finding was tempered by the less than 10-point difference in MDADI scores. The findings of this study underline the limitations of QoL measures as standalone assessments in patients with HNSCC, given their reliance on patient-perceived impairment. While subjective QoL is a crucial aspect of evaluating therapeutic success and patient-centric outcomes, it may fail to capture critical clinical details such as silent aspirations. Consequently, QoL assessments should be augmented by objective evaluations of swallowing function in clinical research and practice to ensure a holistic understanding of patient well-being and treatment impact.

Establishing safe high hydrostatic pressure devitalization thresholds for autologous head and neck cancer vaccination and reconstruction.

High hydrostatic pressure specifically devitalizes cells and tissues without major changes in their molecular structure. Hence, high hydrostatic pressure may enhance the development of whole-cell anti-tumor vaccines, representing tumor heterogeneity and thus (neo-) antigen diversity. Moreover, safe devitalization of tumor-infiltrated supporting tissue may facilitate reimplantation for functional reconstruction. However, precise high hydrostatic pressure thresholds for safe cancer cell killing are unknown. Here, we show that high hydrostatic pressure of at least 450 MPa is necessary to safely devitalize head and neck squamous cell cancer. A pressure of 300 MPa, which has been used frequently in cancer vaccine preparation, resulted in partial devitalization with 27% live cells in flow cytometry and 4% remaining autofluorescence in cell culture after one week. The remaining cells could form vital tumors in the chorioallantoic membrane assay. In contrast, 450 MPa killed all cells in vitro and prevented tumor outgrowth in ovo. The effectiveness of 450 MPa was attributed to the induction of DNA double-strand breaks, independent of apoptosis, autophagy, or methuosis. Furthermore, 450 MPa continued to induce immunogenic cell death. Our results demonstrate that 450 MPa of high hydrostatic pressure induces safe and sustained devitalization of head and neck cancer cells and tissues. Because of the heterogeneity in pressure resistance, we propose our approach as a starting point for determining the precise thresholds for other cancer entities. Further studies on head and neck cancer should focus on immunological co-cultures, combinations of immune checkpoint inhibition, and accurate anatomical reconstruction with pressure-treated autografts.