BACKGROUND:Demographic changes are influencing the spectrum of patients seen in ear, nose, and throat medicine. Geriatric tumor patients vary greatly in terms of their comorbidities and physical function, requiring an adaptation of typical treatment concepts. OBJECTIVE:The aim of this work was to examine the current prospects for treating head and neck tumors in geriatric patients, with a focus on survival, functionality, and quality of life. MATERIALS AND METHODS:A narrative literature search and discussion were conducted, considering the aforementioned question. The graphics were created using Windows PowerPoint 2019 (Microsoft, Redmond, WA, USA), Servier Medical Art (Servier, Munich, Germany). RESULTS:Patients with head and neck tumors who are older than 70 years survive for significantly shorter periods than younger patients (under 70 years), with a median survival time of 35 months. They generally require comprehensive, personalized treatment plans that extend well beyond acute oncological intervention to achieve optimal therapeutic outcomes. CONCLUSION:The increased complexity of cases involving geriatric patients, coupled with their growing numbers, requires expanded collaboration with geriatric screening and intervention programs, the development of the necessary infrastructure, staff training, and the inclusion of this patient group in future studies.

ABSTRACT Purpose The prognostic relevance of gender in head and neck cancer is often neglected. In contrast, the more favorable prognosis of human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinoma (OPSCC) is well recognized, and de‐escalation strategies are increasingly being tested in clinical trials. In this study, we focused on the prognostic significance of gender to clarify whether it should be given more attention. Patients and Methods We requested data on patients with newly diagnosed head and neck cancer between 2002 and 2017 from the German Center of Cancer Registry (n = 212,920). First, we focused on sex‐specific survival according to primary tumor site in a nationwide context. Second, we examined a local dataset of 462 OPSCC patients, diagnosed at the University Hospitals of Ulm and Lübeck between 2005 and 2018 and followed up until 2024. Here we compared the prognostic value of sex with HPV status, alcohol consumption, and smoking habits (these parameters were not available at national level). Results In the nationwide analysis, women showed better survival in all head and neck primary tumor sites studied. The mean survival difference was greatest in patients with OPSCC (1.3 years; p < 0.0001), followed by patients with nasopharyngeal carcinoma (1 year; p < 0.0001). In the subgroup of patients younger than the median age (62.8 years), women lived on mean 1.2 times longer than men (p < 0.0001). Besides, in the local dataset, men with HPV‐positive OPSCC did not have a better prognosis than women, even when HPV‐negative (p = 0.426). However, the prognostic effect of female sex may be attenuated in patients with high tobacco use; in this scenario, no sex‐related difference in survival was found (p = 0.56). Conclusion Sex‐specific differences in survival, especially in OPSCC and nasopharyngeal cancers, suggest the implementation of gender‐sensitive oncology regarding prevention, treatment, and aftercare.

Der demografische Wandel führt auch zu einer Veränderung des Patientenspektrums im Fachgebiet der Hals-Nasen-Ohren-Heilkunde. Geriatrische Tumorpatienten variieren stark in ihrer Komorbidität und körperlichen Funktion, was eine Anpassung typischer Behandlungskonzepte erfordert. Ziel der Arbeit war die Prüfung der derzeitigen Therapieerfolgsaussichten geriatrischer Kopf-Hals-Tumorpatienten mit dem Schwerpunkt Überleben, Funktionalität und Lebensqualität. Es erfolgte die Durchführung einer narrativen Literaturrecherche unter Berücksichtigung der genannten Fragestellung und Diskussion von Handlungsempfehlungen. Die Grafikerstellung wurde mit Windows Power Point 2019 (Fa. Microsoft, Redmond/WA, USA) und Servier Medical Art (Fa. Servier, München, Deutschland) durchgeführt. Kopf-Hals-Tumorpatienten, die älter als 70 Jahre sind, überleben mit im Median 35 Monaten signifikant kürzere Zeit als jüngere Patienten (< 70 Jahre). Sie benötigen für ein optimales Therapieergebnis i. d. R. individualisierte, umfassende Therapiekonzepte, die weit über die akutonkologische Intervention hinausgehen. Die erhöhte Fallkomplexität geriatrischer Patienten und die steigende Anzahl erfordert den Ausbau von Kooperationen mit geriatrischen Screening- und Interventionsprogrammen, entsprechender Infrastruktur und Personalschulung sowie die Integration dieser Patientengruppe in kommende Studien.

Background:The health-related quality of life (HRQoL) of patients with locally advanced head and neck squamous cell carcinoma (LA HNSCC) is impacted by both disease- and treatment-related factors. Treatments that preserve and maximize HRQoL in this setting represent a substantial unmet need. Methods:KEYNOTE-412 (NCT03040999) was a randomized, double-blind, placebo-controlled phase 3 study of pembrolizumab plus chemoradiotherapy (CRT) versus placebo plus CRT for maintenance therapy in participants with treatment-naïve LA HNSCC. Patient-reported outcomes (PROs) assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EORTC QLQ Head and Neck 35 (H&N35) were pre-specified secondary endpoints and administered at baseline and throughout the study. Least squares mean (LSM) change from baseline was assessed using a constrained longitudinal data analysis model. No formal statistical significance testing was performed. Results:The PRO analysis population included 395 participants randomized to receive pembrolizumab plus CRT and 397 to receive placebo plus CRT. Completion rates for all assessed PROs were >95% at baseline and >66% at week 45. LSM change from baseline to week 45 was similar between groups across EORTC QLQ-C30 and QLQ-H&N35 subscale scores. There were no notable differences in empirical mean change or the proportion of participants with improvement, stability, or deterioration from baseline to week 45 between treatment groups. Conclusion:The addition of pembrolizumab to CRT did not meaningfully impact HRQoL in participants with LA HNSCC.

BACKGROUND:Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is becoming increasingly important in head and neck oncology. At this year's conference of the American Society of Clinical Oncology (ASCO), a large number of papers were presented on the topic of HPV-associated HNSCC, particularly with regard to neoadjuvant treatment approaches, radiation de-escalation strategies, therapeutic vaccines, and treatment monitoring. In this context, study results on the treatment of HPV-related recurrent respiratory papillomatosis (RRP) were also presented. OBJECTIVE:Based on contributions to the 2024 ASCO Annual Meeting, an insight into the latest developments in HPV-associated diseases of the head and neck is provided. METHODS:The papers were reviewed for clinical relevance and contextualized based on current therapeutic concepts. RESULTS AND CONCLUSION:A large number of studies on liquid biopsies (LB) were presented. It was shown that although the methods for analyzing LBs for HPV-positive patients are well developed and can be used for diagnostics, risk classification, treatment management, or tumor follow-up, the methods vary considerably, and their clinical application has not yet been sufficiently validated. With regard to therapeutic HPV vaccination, three large studies were presented for the treatment of recurrent/metastatic HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). The only randomized study was on the vaccine ISA101b (peltopepimut-S) and did not reach its primary endpoint; however, the vaccine seemed to be highly effective in patients with a combined positive score (CPS) ≥ 20. Furthermore, data from a phase I study on PRGN2012, an adenovirus-based immunotherapy used therapeutically for the treatment of recurrent respiratory papillomatosis (RRP), were presented. PRGN2012 led to a reduction in surgical interventions for RRP, and the US Food and Drug Administration (FDA) designated PRGN2012 as a breakthrough therapy and orphan drug. However, the vaccine is not yet approved for the treatment of RRP.

The availability of virtual reality (VR) in the medical field has been rapidly increasing in the past years. Here we investigate to which extent the VR headset can lead to a reduction in anxiety and pain in patients during surgical procedures under local anesthesia in the head and neck region. Patients were divided into a study group (N = 67) and a control group (N = 28). The study group used a VR headset during surgical procedures in the head and neck region under local anaesthesia. Before and after surgery, the influence of the VR headset on perioperative anxiety was assessed using the State-Trait-Anxiety-Inventory (STAI) in both groups. The use of a VR headset leads to a significant reduction in perioperative anxiety. The anxiety scores measured by means and ranks of the STAI were significantly decreased (p = .002). However, 14/67 (20.9%) of the patients wearing the VR headset also reported higher intraoperative tension. No technical complications occurred intraoperatively. 48/67 (71.7%) of the patients would be less apprehensive about a future operation when using a VR headset and 58/67 (86.6%) would further recommend the use of a VR headset to other patients. In addition to a trusting surgeon-patient relationship and the use of sufficient local anaesthesia, the use of a VR headset as a method of distraction can further reduce the intraoperative anxiety of patients.

Purpose/Objective(s)The phase 3 KEYNOTE-412 study (NCT03040999), pembro + CRT (pembro arm) showed a trend toward improved EFS vs placebo + CRT (pbo arm) in pts with LA HNSCC, although the difference was not statistically significant (HR, 0.83 [95% CI, 0.68-1.03]; P=0.0429 [superiority threshold, P=0.0242]). Prespecified HRQoL outcomes from KEYNOTE-412 are presented.Materials/MethodsPts aged ≥18 yrs with LA HNSCC were randomly assigned 1:1 to pembro 200 mg IV once Q3W or matching pbo + CRT. Pts received 1 priming dose of pembro/pbo 1 week before CRT followed by 2 doses of pembro/pbo during CRT and maintenance pembro/pbo for up to 14 doses. Prespecified secondary end points were mean change from baseline (BL) in EORTC QLQ-C30 global health status/quality of life (GHS/QoL) and physical functioning scores as well as EORTC QLQ-H&N35 pain, problems with swallowing, and speech scores. Prespecified exploratory end points included rate of improvement, stability, and deterioration, and mean change from BL in other prespecified scales of QLQ-C30, QLQ-H&N35, and EQ-5D VAS. Analysis population included pts who received ≥1 dose of treatment and completed ≥1 HRQoL assessment for a specific end point. Analysis was done at week 45 when respective completion and compliance rates of ≥60% and ≥80% were met per blinded data review. Treatment difference (least squares mean [LSM] change from BL) was estimated from a constrained longitudinal data analysis method.ResultsCompletion and compliance rates were >95% at BL for all measures. Completion rates were >60% and compliance rates were >80% for all measures at week 45. LSM change from BL to week 45 for pembro vs pbo was 1.95 (95% CI, −0.10 to 4.00) vs 6.08 (95% CI, 4.02 to 8.13) for QLQ-C30 GHS/QoL (LSM difference: −4.13 [95% CI, −6.73 to −1.53]) and −5.54 (95% CI, −7.34 to −3.73) vs −3.46 (95% CI, −5.26 to −1.66) for QLQ-C30 physical functioning (LSM difference: −2.07 [95% CI: −4.51 to 0.36]). No meaningful differences in LSM change from BL to week 45 were observed between treatment arms for QLQ-H&N35 pain (1.44 [95% CI, −1.27 to 4.15]), problems with speech (−1.27 [95% CI, −4.60 to 2.07]), and swallowing (−0.31 [95% CI, −3.75 to 3.13]) scales or in EQ-5D VAS (−1.44 [95% CI, −3.74 to 0.85]). Similar percentages of pts for the pembro vs pbo arms had improved or stable scores for QLQ-C30 GHS/QoL (43.0% vs 47.6%) and QLQ-H&N35 pain (49.9% vs 50.3%), problems with speech (40.3% vs 41.4%), and swallowing (34.4% vs 34.3%) scales.ConclusionPatient-reported outcomes and disease symptom scores were generally similar between pembro and pbo arms, suggesting addition of pembro to CRT did not meaningfully impact HRQoL at week 45 in pts with LA HNSCC.

Humane-Papillomavirus(HPV)-assoziierte Kopf-Hals-Karzinome („head and neck squamous cell carcinoma“, HNSCC) nehmen einen zunehmenden Stellenwert in der Kopf-Hals-Onkologie ein. Beim diesjährigen Kongress der Amerikanischen Gesellschaft für Onkologie (American Society of Clinical Oncology, ASCO) wurden eine Vielzahl an Arbeiten zum Thema HPV, insbesondere hinsichtlich neoadjuvanter Therapieansätze, Strahlendeeskalationsstrategien, therapeutischer Vakzine und Therapiemonitoring vorgestellt. In diesem Rahmen wurden auch Studienergebnisse zur Behandlung der HPV-assoziierten rezidivierenden respiratorischen Papillomatose (RRP) vorgestellt. Anhand von Beiträgen der ASCO-Jahrestagung 2024 wird ein Einblick in die neuesten Entwicklungen bei HPV-assoziierten Erkrankungen des Kopf-Hals-Bereichs gegeben. Die Beiträge wurden auf ihre klinische Relevanz geprüft und mit aktuellen Therapiekonzepten in Kontext gesetzt. Es wurde eine Vielzahl an Studien zu Flüssigbiopsien („liquid biopsy“, LB) vorgestellt. Hierbei zeigte sich, dass die Methoden zur Analyse von LB für HPV-positiven Patienten zwar weit entwickelt sind und der Diagnostik, Risikoklassifikation, Therapiesteuerung oder Tumornachsorge dienen können, allerdings variieren die Methoden erheblich, und die klinische Anwendung ist bislang nicht ausreichend validiert. Hinsichtlich therapeutischer HPV-Impfungen wurden 3 große Studien für die Behandlung von rekurrenten/metastasierten HPV-positiven Oropharynxkarzinomen („oropharyngeal squamous cell carcinoma“, OPSCC) vorgestellt. Die einzige randomisierte Studie gab es zu dem Impfpräparat ISA101b (Peltopepimut-S), sie erreichte ihren primären Endpunkt nicht, hatte jedoch eine hohe Effektivität bei Patienten mit einem Combined Positive Score (CPS) ≥ 20. Darüber hinaus wurden die Daten einer Phase-I-Studie zu PRGN2012 vorgestellt, einer adenovirusbasierten Immuntherapie, die therapeutisch zur Behandlung der rezidivierenden respiratorischen Papillomatose (RRP) eingesetzt wurde. PRGN2012 führte zu einer Reduktion chirurgischer Eingriffe für die RRP, und die US-amerikanische Food and Drug Administration (FDA) bewertete PRGN2012 als „breakthrough therapy“ und „orphan drug“. Allerdings ist die Impfung derzeit noch nicht zur Behandlung der RRP zugelassen.

PD-1 antibodies have become standard of care in the treatment of recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) in first or second-line palliative treatment. After 4 years of follow up, 17% of the initial Keynote-48 study population is alive. In clinical routine, it remains an unresolved question how to deal with the situation of complete remission concerning treatment continuation. In a retrospective case analysis we collected patients with HNSCC who experienced complete or very good partial remission under PD-1 inhibition. A very good partial remission was defined as a residual tumor substrate without contrast enhancement on CT and no change in residual tumor mass within the last 6 months. 53 patients derived from 6 centers in Germany were identified. PD-L1 CPS was 0 in 2 pts, 1-20 in 13 pts. >20 in 13 pts and missing in 25. Nivolumab was given in 28 pts. (52%), pembrolizumab in 18 pts (34%), pembrolizumab/chemotherapy in 3 and other immunotherapies in 4 pts. At the first staging after therapy initiation, 28 pts (52%) had a partial remission (PR) and 6 (11%) a complete remission (CR). The median time to very good partial or CR was 7 months. Of the 53 patients, 17 remain on treatment to date of data collection. 36 patients discontinued treatment, 11 because of toxicity. Of the 36 patients, 9 experienced disease progression of whom 7 patients were treated again with PD-1 inhibitor. First course of ICI had a median duration of 25 months. The majority of patients (75%) remained in remission after treatment discontinuation with a median follow up of 7 months. Of the 7 patients who were re-challenged 4 had a PR, 1 SD, 1 PD and 1 missing. To our knowledge, this is the first case collection of patients with complete or very good partial remission of head and neck SCC patients receiving PD-1 inhibitors for whom treatment discontinuation may be considered. After treatment discontinuation, the majority of patients remain in remission and 71% of patients experience disease control when re-exposed to PD-1 inhibitors. Extension of this case collection and long-term follow-up is needed to guide patient counseling in regard to the question of safe treatment discontinuation.

Das vorrangige Ziel der Tumornachsorge bei in kurativer Intention behandelten Kopf-Hals-Tumorpatienten stellt die frühzeitige Diagnose und Therapie eines Lokalrezidivs dar. Auch sollen metachrone Zweitkarzinome oder eine mögliche Fernmetastasierung zeitnah detektiert werden, um ggf. eine palliative Therapie initiieren zu können. Die Literatur zeigt, dass die Mehrzahl der Rezidive innerhalb der ersten 2 Jahre nach abgeschlossener Tumortherapie auftreten. Die Detektion erfolgt hierbei entweder durch den Patienten selbst bei entsprechend neu aufgetretener Symptomatik, die HNO-ärztliche Spiegeluntersuchung oder durch Auffälligkeiten in der Kontrollbildgebung. Die klinische Untersuchung mit Endoskopie der oberen Schluck- und Atemwege mit symptomorientierter Anamnese, die B‑Bild-Sonographie der Halsweichteile und ergänzende radiologische Staging-Untersuchungen der Fernmetastasierungslokalisationen stellen die 3 wesentlichen Säulen der Tumornachsorge bei Kopf-Hals-Tumoren dar und werden i. d. R. über die Dauer von 5 Jahren durchgeführt. Für die ersten 2,5 Jahre des Nachsorgezeitraums sollten Kontrolluntersuchungen im 3‑Monats-Intervall erfolgen. Nach unauffälliger erster Hälfte des Nachsorgezeitraums können die Intervalle auf 6–12 Monate ausgedehnt werden. Die Modalität des jährlichen radiologischen Restagings orientiert sich an der Primärtumorregion und Ausdehnung und sollte patientenindividuell geplant werden. Neben an Kopf-Hals-Tumorzentren tätigen und niedergelassenen HNO-Fachärzten sind u. a. auch Strahlentherapeuten, Radiologen, Mund-Kiefer-Gesichts-Chirurgen, Nuklearmediziner, Dermatologen, Logopäden, Physio- und Ergotherapeuten, Phoniater, Ernährungsberater und Psychoonkologen an der Nachsorge dieser Tumorentität beteiligt. Letztlich dient die onkologische Nachsorge auch dem Ziel, die Lebensqualität der betroffenen Patienten zu optimieren, indem therapieassoziierte Nebenwirkungen erkannt und behandelt werden.

Pembrolizumab (pembro) and pembro + platinum + 5-FU (pembro + chemo) are standard-of-care options alongside cetuximab-based regimens such as EXTREME (cetuximab + platinum + 5-FU) for R/M HNSCC, depending on PD-L1 expression and clinical circumstances, but optimal sequencing has not been defined. We present OS in pts with PD-L1+ R/M HNSCC who received first-line (1L) pembro or pembro + chemo followed by cetuximab-based therapy, or EXTREME followed by immunotherapy (IO), in KEYNOTE-048 (NCT02358031). Pts with locally incurable R/M HNSCC were randomly assigned 1:1:1 to 1L pembro, pembro + chemo, or EXTREME. This post hoc exploratory analysis included pts with PD-L1 CPS ≥1 who received second-line (2L) cetuximab-based therapy (cetux) after pembro or pembro + chemo, or 2L IO after EXTREME. Of 882 pts, 170 with PD-L1 CPS ≥1 who received 2L cetux or IO were included (1L pembro, n = 63; pembro + chemo, n = 37; EXTREME, n = 70). Median follow-up was 69.3 mo (range, 61.2-81.2). Median OS (95% CI) was 15.7 mo (12.3-22.6) for pts who received pembro followed by cetux vs 16.5 mo (13.5-19.8) for EXTREME followed by IO (HR, 1.0; 95% CI, 0.7-1.5); 24-mo OS was 32% vs 31%. Median OS (95% CI) was 22.1 mo (14.0-24.7) for pts who received pembro + chemo followed by cetux vs 16.5 mo (11.5-19.8) for EXTREME followed by IO (HR, 0.7; 95% CI, 0.4-1.0); 24-mo OS was 39% vs 30%. Median OS (95% CI) was 16.6 mo (13.8-23.2) for all pts who received pembro or pembro + chemo (n = 100) followed by cetux vs 16.5 mo (13.5-19.8) for EXTREME followed by IO (HR, 0.9; 95% CI, 0.6-1.2); 24-mo OS was 34% vs 31%. Of pts receiving pembro or pembro + chemo, 13 received subsequent cetux monotherapy and 87 received cetux + chemo. In this post hoc exploratory analysis of KEYNOTE-048, OS was longer for pts who received pembro + chemo followed by cetux vs EXTREME followed by IO and was similar for pts who received pembro followed by cetux vs EXTREME followed by IO. Clinical factors may have contributed to different use of 2L therapies by treatment arm. These findings, in addition to the primary analysis of KEYNOTE-048, support 1L pembro and pembro + chemo in PD-L1–positive R/M HNSCC.