Prospects for online adaptive radiation therapy (ART) for head and neck cancer.

BACKGROUND: The aim of the present study is to examine the impact of kV-CBCT-based online adaptive radiation therapy (ART) on dosimetric parameters in comparison to image-guided-radiotherapy (IGRT) in consecutive patients with tumors in the head and neck region from a prospective registry. METHODS: The study comprises all consecutive patients with tumors in the head and neck area who were treated with kV-CBCT-based online ART or IGRT-modus at the linear-accelerator ETHOS™. As a measure of effectiveness, the equivalent-uniform-dose was calculated for the CTV (EUDCTV) and organs-at-risk (EUDOAR) and normalized to the prescribed dose. As an important determinant for the need of ART the interfractional shifts of anatomic landmarks related to the tongue were analyzed and compared to the intrafractional shifts. The latter determine the performance of the adapted dose distribution on the verification CBCT2 postadaptation. RESULTS: Altogether 59 consecutive patients with tumors in the head-and-neck-area were treated from 01.12.2021 to 31.01.2023. Ten of all 59 patients (10/59; 16.9%) received at least one phase within a treatment course with ART. Of 46 fractions in the adaptive mode, irradiation was conducted in 65.2% of fractions with the adaptive-plan, the scheduled-plan in the remaining. The dispersion of the distributions of EUDCTV-values from the 46 dose fractions differed significantly between the scheduled and adaptive plans (Ansari-Bradley-Test, p = 0.0158). Thus, the 2.5th percentile of the EUDCTV-values by the adaptive plans amounted 97.1% (95% CI 96.6-99.5%) and by the scheduled plans 78.1% (95% CI 61.8-88.7%). While the EUDCTV for the accumulated dose distributions stayed above 95% at PTV-margins of ≥ 3 mm for all 8 analyzed treatment phases the scheduled plans did for margins ≥ 5 mm. The intrafractional anatomic shifts of all 8 measured anatomic landmarks were smaller than the interfractional with overall median values of 8.5 mm and 5.5 mm (p < 0.0001 for five and p < 0.05 for all parameters, pairwise comparisons, signed-rank-test). The EUDOAR-values for the larynx and the parotid gland were significantly lower for the adaptive compared with the scheduled plans (Wilcoxon-test, p < 0.001). CONCLUSIONS: The mobile tongue and tongue base showed considerable interfractional variations. While PTV-margins of 5 mm were sufficient for IGRT, ART showed the potential of decreasing PTV-margins and spare dose to the organs-at-risk.

[Perioperative medical prophylaxis of venous thromboembolic events in head and neck surgery : A retrospective study and recommendations]. / Medikamentöse Thromboseprophylaxe bei Kopf-Hals-Operationen : Eine retrospektive Analyse und Handlungsempfehlung.

BACKGROUND: In the authors' department, a newly implemented clinical algorithm for application of perioperative thrombosis prophylaxis in head and neck surgery recommends restrictive handling of anticoagulants. This retrospective study aims to evaluate the algorithm by comparing incidences of venous thromboembolic events (VTE) and surgical revisions due to postoperative hemorrhage. MATERIALS AND METHODS: Perioperative incidences of deep vein thrombosis and pulmonary embolism as well as surgical revisions due to postoperative hemorrhage after head and neck surgery were determined based on all patients operated in the department over a period of 36 months. The incidences before (group I) and after (group II) implementation of the restrictive algorithm were compared. RESULTS: A total of 9276 patients were included. The incidences of VTE (0.12%) and surgical revisions due to postoperative hemorrhage (1.4%) were low. Incidences of VTE were non-significantly higher in group II (0.16%) than in group I (0.08%; p > 0.45, chi-square-test). Case analysis revealed that this difference was not due to implementation of the restrictive algorithm. The incidence of surgical revision due to postoperative hemorrhage was identical in the two groups (1.4%). CONCLUSION: After restricting the indication for thrombosis prophylaxis, the incidence of VTE or surgical revision due to postoperative hemorrhage did not change significantly. The provided clinical algorithm represents a low-risk and low-cost strategy of perioperative risk stratification.

[Stimulatory and inhibitory signaling pathways of the T cell-APC interaction and the effect of TLR agonists on APCs]. / Stimulierende und inhibierende Signalwege der APZ- und T-Zell-Interaktion sowie Einfluss von TLR-Agonisten auf APZ.

BACKGROUND: CD8+ cells are key players in the identification and elimination of cancer cells. Cancers can escape an effective T cell response by inducing an exhausted cell state, which limits the cytotoxic capacity of the effector cells. Among other mechanisms, new checkpoint inhibitors reactivate exhausted, dysfunctional T cells. CD8+ T cells can eliminate tumor cells after presentation of tumor-specific antigens via antigen-presenting cells (APCs). APC-mediated tumor recognition is mainly stimulated by Toll-like receptors (TLRs). OBJECTIVE: This study investigates the effect of TLR agonists on APCs as well as stimulatory and inhibitory signaling pathways of the T cell-APC interaction. MATERIALS AND METHODS: Gene expression of interleukin (IL)12 and programmed death ligand 1 (PD-L1) was analyzed by quantitative polymerase chain reaction (qPCR) after 0, 8, 24, and 48 h of CD14+ cell stimulation with CpG. Protein expression of inhibitor of nuclear factor kappa B (IκBα) after CpG stimulation was investigated by western blot. CD8+ T cells were stimulated for 72 h with or without programmed cell death protein 1 (PD-1) checkpoint blockade and analyzed for expression of PD­1, Tim­3, CTLA4, and Lag3 by flow cytometry. RESULTS: TLR stimulation (by unmethylated CpG DNA) of APCs upregulates immunostimulatory signals such as IL12 expression but also activates immunoinhibitory signaling pathways such as PD-L1 expression. This signaling is NF-κB dependent. After blockade of the PD-1/PD-L1 signaling pathway, overexpression of other immune checkpoint inhibitory receptors was observed-a potential explanation for lacking therapeutic responses after TLR stimulation with PD­1 checkpoint blockade. CONCLUSION: TLR stimulation causes APCs in the tumor microenvironment to upregulate PD-L1 in an NF-κB-mediated fashion, thereby contributing to CD8+ T cell exhaustion. The effect of PD­1 blockade after TLR stimulation might be impaired due to upregulation of other checkpoint inhibitors.

[Head and neck cancer in the elderly-current aspects]. / Tumorerkrankungen des Kopf-Hals-Bereichs im höheren Lebensalter ­ aktuelle Aspekte.

BACKGROUND: The treatment of head and neck cancer is dominated by surgery and radiochemotherapy, which is in part associated with high morbidity. In elderly patients, however, the otorhinolaryngologist often has to question the rationality of invasive treatment. Although the proportion of geriatric patients with head and neck tumors is increasing, the paucity of data means that there are few consistent standards and recommendations in the literature and guidelines. OBJECTIVE: The aim of this paper is to provide concrete clinical recommendations for geriatric patients with head and neck tumors based on a systematic literature search. MATERIALS AND METHODS: A keyword-based literature search was performed to present the current level of evidence and provide a clinical algorithm. RESULTS: In addition to age, the pretreatment dispositional evaluation of geriatric patients should include psychosocial, functional, and medical (patient history) comorbidities. For pretreatment risk stratification, an algorithm was created on the basis of these data for individual evaluation of the patient's pretreatment risk. CONCLUSION: Pretreatment risk stratification of geriatric patients with head and neck malignancies is of high relevance for the individual decision for or against invasive treatment, but the currently available evidence is limited. This paper is based on a systematic literature review and provides a clinical algorithm for otorhinolaryngologists and head and neck surgeons.

Regional recurrence in a case series of patients with carcinoma of the nasal cavity - therapeutic implications.

INTRODUCTION: Surgery is the primary treatment option for squamous cell carcinomas of the nasal cavity (NCSCC). Nodal involvement is rare at the time of initial diagnosis, and the role of diagnostic neck dissection as well as potential adjuvant irradiation of the neck remains controversial. The objective of this study was to assess the oncologic outcomes of patients with NCSCC with special emphasis on cervical lymph node treatment and recurrence. METHODS: 37 previously untreated patients were included in this study. Demographic data, tumor characteristics, therapeutic management, and clinical outcome were analyzed. RESULTS: Patients with advanced stage tumors were slightly overrepresented in this study and overall 3-year disease-free survival was 63%. A surgical treatment approach was pursued in 89% (n=33) of patients. After total rhinectomy, there were no cases of local recurrence. Overall, 12% (n=4) of all surgically treated patients developed local recurrence. While in 45% of patients (n=15), neck dissection was performed at the time of tumor resection, initial lymph node metastasis was histologically confirmed in only 6% (n=2) of surgically treated patients. Cervical lymph node recurrence occurred in 18% (n=6) of patients, predominantly those with advanced stage tumors, despite prior treatment of the neck. CONCLUSION: Excellent local control is achievable for patients with NCSCC, especially with radical tumor resection. While cervical lymph node metastasis is rare at the time of diagnosis, regional lymph node recurrence needs to be taken into consideration when planning therapy and follow-up. Multimodal treatment of the neck may be required for patients with advanced stage tumors.

[Prophylaxis of venous thromboembolic events in head and neck surgery]. / Die Prophylaxe venöser Thromboembolien bei Kopf­Hals­Operationen.

BACKGROUND: Application of perioperative thrombosis prophylaxis in head and neck surgery lacks consistent standards in Germany. Due to sparse data, the latest German S3 guideline concerning prophylaxis of thromboembolic events recommends a restrictive handling of anticoagulants in head and neck surgery, with few specific recommendations. OBJECTIVE: The aim of this paper is to provide concrete clinical recommendations based on a systematic literature review and the S3 guidelines. MATERIALS AND METHODS: A keyword-based literature search was performed and the German S3 guideline "Prophylaxis of Venous Thromboembolic Events" was used to state the current level of evidence and provide a clinical algorithm. RESULTS: Eight additional cohort studies dealing with the incidence of thromboembolic events in head and neck surgery were identified. There were no randomized controlled trials. In the proposed algorithm, a classification of dispositional (patient history) and expositional (operation time) risk into three groups enables preoperative risk evaluation indicating the individual demand for prophylaxis. In short operations without major tissue traumatization, routine drug-based thrombosis prophylaxis is not necessary, provided no third-grade risk factors (earlier thromboembolic event, coagulopathy, or malignant disease) are present. Low molecular weight heparins should be used as anticoagulants for drug-based prophylaxis. CONCLUSION: Prophylaxis of thromboembolic events in head and neck surgery is of high clinical relevance but there is currently limited evidence regarding its implementation. This paper is based on a systematic literature review and provides a clinical algorithm for head and neck surgeons.

The neural correlates of affect reading: an fMRI study on faces and gestures.

As complex social beings, people communicate, in addition to spoken language, also via nonverbal behavior. In social face-to-face situations, people readily read the affect and intentions of others in their face expressions and gestures recognizing their meaning. Importantly, the addressee further has to discriminate the meanings of the seen communicative motor acts in order to be able to react upon them appropriately. In this functional magnetic resonance imaging study 15 healthy non-alexithymic right-handers observed video-clips that showed the dynamic evolution of emotional face expressions and gestures evolving from a neutral to a fully developed expression. We aimed at disentangling the cerebral circuits related to the observation of the incomplete and the subsequent discrimination of the evolved bodily expressions of emotion which are typical for everyday social situations. We show that the inferior temporal gyrus and the inferior and dorsal medial frontal cortex in both cerebral hemispheres were activated early in recognizing faces and gestures, while their subsequent discrimination involved the right dorsolateral frontal cortex. Interregional correlations showed that the involved regions constituted a widespread circuit allowing for a formal analysis of the seen expressions, their empathic processing and the subjective interpretation of their contextual meanings. Right-left comparisons revealed a greater activation of the right dorsal medial frontal cortex and the inferior temporal gyrus which supports the notion of a right hemispheric dominance for processing affective body expressions. These novel data provide a neurobiological basis for the intuitive understanding of other people which is relevant for socially appropriate decisions and intact social functioning.