To determine whether a single dose of double immune checkpoint blockade (induction chemoimmunotherapy (ICIT)) adds benefit to induction single-cycle platinum doublet (induction chemotherapy (IC)) in locally advanced head and neck squamous cell carcinoma (HNSCC), patients treated with cisplatin 30 mg/m² d1-3 and docetaxel 75 mg/m² d1 combined with durvalumab 1500 mg fixed dose d5 and tremelimumab 75 mg fixed dose d5 (ICIT) within the CheckRad-CD8 trial were compared with a retrospective cohort receiving the same chemotherapy (IC) without immunotherapy. The endpoint of this analysis was the complete response rate (CR). A total of 53 patients were treated with ICIT and 104 patients with IC only. CR rates were 60.3% for ICIT and 40.3% for IC (p = 0.018). In the total population (n = 157), the most important predictor to achieve a CR was treatment type (OR: 2.21 for ICIT vs. IC; p = 0.038, multivariate analysis). The most diverse effects in CR rates between ICIT and IC were observed in younger (age ≤ 60) patients with HPV-positive OPSCCs (82% vs. 33%, p = 0.176), while there was no difference in older patients without HPV-positive OPSCCs (53% vs. 48%). The analysis provides initial evidence that ICIT could result in higher CR rates than IC. Young patients with HPV-positive OPSCCs may have the greatest benefit from additional immune checkpoint inhibitors.

Superparamagnetic iron oxide nanoparticles (SPIONs) feature distinct magnetic properties that make them useful and effective tools for various diagnostic, therapeutic and theranostic applications. In particular, their use in magnetic drug targeting (MDT) promises to be an effective approach for the treatment of various diseases such as cancer. At the cellular level, SPION uptake, along with SPION-mediated toxicity, represents the most important prerequisite for successful application. Thus, the present study determines SPION uptake, toxicity and biocompatibility in human head and neck tumor cell lines of the tongue, pharynx and salivary gland. Using magnetic susceptibility measurements, microscopy, atomic emission spectroscopy, flow cytometry, and plasma coagulation, we analyzed the magnetic properties, cellular uptake and biocompatibility of two different SPION types in the presence and absence of external magnetic fields. Incubation of cells with lauric acid and human serum albumin-coated nanoparticles (SPION^LA-HSA) resulted in substantial particle uptake with low cytotoxicity. In contrast, uptake of lauric acid-coated nanoparticles (SPION^LA) was substantially increased but accompanied by higher toxicity. The presence of an external magnetic field significantly increased cellular uptake of both particles, although cytotoxicity was not significantly increased in any of the cell lines. SPIONs coated with lauric acid and/or human serum albumin show different patterns of uptake and toxicity in response to an external magnetic field. Consequently, the results indicate the potential use of SPIONs as vehicles for MDT in head and neck cancer.

While the treatment of squamous cell carcinoma of the head and neck (HNSCC) with radiotherapy (RT) is complemented more and more by immunotherapy in clinical trials, little is known about the impact of the human papillomavirus (HPV) status or the applied RT scheme on the immune phenotype of the tumor cells. Therefore, we aimed to examine the impact of the HPV status of four human HNSCC cell lines on cell death and the expression of immune checkpoint molecules (ICMs) after RT with either hypofractionation irradiation (5x3.0Gy) or a high single dose (1x19.3Gy) via multicolor flow cytometry and quantitative PCR at an early time point after therapy. In our study, 5x3.0Gy RT induced high numbers of early and late apoptotic cells independent of the HPV status, but necrosis was only increased in the HPV-positive UM-Scc-47 cells. Generally, the immune stimulatory ICMs (CD70, CD137-L, ICOS-L) were less affected by RT compared to the immune suppressive ones (PD-L1, PD-L2, and the herpesvirus entry mediator (HVEM)). A significant higher surface expression of the analyzed ICMs was found after hypofractionated RT compared to a single high dose; however, regardless of the HPV status, with the exception of ICOS-L. Here, HPV-positive HNSCC tumor cells showed a stronger response to 5x3.0Gy than HPV-negative ones. On the RNA level, only minor alterations of ICMs were observed following RT, with the exception of the HPV negative cell line CAL33 treated with 5x3.0Gy, where PD-L2, HVEM and CD70 were significantly increased. We conclude that the HPV status may not distinctly predict immunological responses following RT, and thus cannot be used as a single predictive marker for therapy responses in HNSCC. In contrast, the patient-specific individual expression of ICMs following RT is preferable for the targeted patient selection for immune therapy directed against distinct ICM.

Mucus consistency affects voice physiology and is connected to voice disorders. Nevertheless, the rheological characteristics of human laryngeal mucus from the vocal folds remain unknown. Knowledge about mucus viscoelasticity enables fabrication of artificial mucus with natural properties, more realistic ex-vivo experiments and promotes a better understanding and improved treatment of dysphonia with regard to mucus consistency. We studied human laryngeal mucus samples from the vocal folds with two complementary approaches: 19 samples were successfully applied to particle tracking microrheology (PTM) and five additional samples to oscillatory shear rheology (OSR). Mucus was collected by experienced laryngologists from patients together with demographic data. The analysis of the viscoelasticity revealed diversity among the investigated mucus samples according to their rigidity (absolute G′ and G″). Moreover some samples revealed throughout solid-like character (G′ > G″), whereas some underwent a change from solid-like to liquid-like (G′ < G″). This led to a subdivision into three groups. We assume that the reason for the differences is a variation in the hydration level of the mucus, which affects the mucin concentration and network formation factors of the mucin mesh. The demographic data could not be correlated to the differences, except for the smoking behavior. Mucus of predominant liquid-like character was associated with current smokers.

Importance Up to 80% of patients with head and neck cancer undergoing ablative surgery and neck dissection develop postoperative pain with detrimental effects on quality of life that also contributes to neuropathic and chronic postoperative pain. Objective To investigate the association of continuous local anesthetic wound infusion with pain management after head and neck surgery. Design, Setting, and Participants This prospective, longitudinal, nonrandomized clinical study carried out in a single tertiary referral center (December 1, 2015, to July 1, 2017) included 2 groups of 30 patients. Patients were consecutively enrolled and presented for ablative head and neck surgery including selective neck dissection and studied from the preoperative through the fourth postoperative day. Interventions The control group was treated according to a standardized escalating oral treatment protocol (ibuprofen, metamizole, opioids). The intervention group was treated with an intraoperatively applied pain catheter (InfiltraLong plus FuserPump, Pajunk, ropivacaine, 0.2%, 3 mL/h) that was removed 72 hours after operating. Main Outcomes and Measures Average and maximum pain intensities on a numeric rating scale; quality of life using the acute version of the validated 36-Item Short Form Survey; and neuropathic pain using the validated 12-Item painDETECT questionnaire. Consumption of opioid and nonopioid analgesics and evaluation of catheter-associated complications. Results During postoperative days 1 through 4, patients of the intervention group (mean [SD] age, 63.2 [13.3 years; 9 [30%] women) experienced lower mean (SD) (1.6 [1.4] vs 2.7 [1.8]; η²_p = 0.09 [0.01-0.21]) and maximum (2.4 [2.2] vs 4.2 [2.0]; η²_p = 0.11 [0.01-0.24]) pain intensities compared with the control group (mean [SD] age, 62.5 [13.6] years; 5 [17%] women). The intervention group also reported less neuropathic pain (mean [SD], 5.4 [3.4] vs 7.6 [5.1]; η²_p = 0.09 [0.004 – 0.22]) and higher quality of life regarding vitality (56.2 [21.5] vs 43.8 [20.9],r = 0.29; 95% CI, 0.01-0.52) and pain (66.8 [27.3] vs 49.5 [27.7],r = 0.31; 95% CI, 0.04-0.54). Patients from the intervention group requested nonopioid analgesics considerably less often (n = 17 [57% ]vs n = 29 [97%]; ϕ = 0.47; 95% CI, 0.30-0.67) associated with a noticeably lower need to escalate pain treatment (n = 3 [10%] vs n = 9 [30%]; mean [SD] ibuprofen dose: 500 [173] mg vs 1133 [650] mg;r = 0.64; 95% CI, 0.02-0.91). No catheter-associated complications were observed. Conclusions and Relevance Continuous anesthetic wound infusion is associated with reduced postoperative pain and decreased demand for analgesics. It therefore expands the treatment options for postoperative pain in head and neck cancer. Trial Registration German Clinical Trials Register:DRKS00009378