[Radiation or Surgery for HPV-positive oropharyngeal cancer? The ORATOR2 Trial - Comparing apples and oranges]. / Strahlentherapie oder Operation bei HPV-positiven Oropharynxkarzinomen? Die ORATOR2-Studie ­ ein Vergleich von Birnen und Äpfeln.

ORATOR2 was a randomized phase II trial aiming to assess an optimal approach for therapy de-escalation in early (T1-T2, N0-N2) human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCC). Radiotherapy (RT) (consisting of a reduced dose of 60 Gy with concurrent weekly cisplatin in N+ patients) was compared to trans-oral surgery (TOS) and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings) in 61 patients. The primary endpoint, overall survival, favored the radiotherapy approach. This was mainly due to 3 mortality events in the surgery arm (2 surgery-related) which resulted in an early trial termination. The authors, who speak on behalf of the German Society of Otorhinolaryngology, Head & Neck Surgery (working group for oncology) warn to draw conclusions for clinical practice pointing out the main shortages/weaknesses of this trial especially in the surgery arm (at least 1 cm margins, recommending re-operation if not achieved, prohibition of regional or free flaps, high rates of tracheotomy, low rate of TLM). Small patient numbers, a highly selected patient cohort and a short follow-up time further limit this study's relevance. Therefore, patients with HPV-related OPSCC should not receive de-escalating (radiation) therapy outside of clinical trials. When deciding between a surgical or a radio-therapeutical approach, patients should be informed about the pros and cons of both modalities after interdisciplinary consent in a tumor board, as long as clinical trial results` (e. g. EORTC 1420) are pending.

[HPV-related oropharyngeal squamous cell carcinoma-Incidence steadily rising]. / Das HPV-positive Oropharynxkarzinom ­ eine Entität mit steigender Inzidenz.

The incidence of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is steadily increasing worldwide and has already exceeded cervical cancer rates in the USA. Due to their tumor biology, HPV-positive tumors of the oropharynx, which have been included in the eighth edition of the AJCC/UICC (American Joint Committee on Cancer/Union Internationale Contre le Cancer) Staging Manual since 2018, represent a separate entity. Following biopsy, diagnostic confirmation is performed by immunohistochemical detection of p16 expression, with p16 acting as a surrogate marker. Therapeutically, surgical and radiotherapeutic approaches are considered equivalent in terms of efficacy. With a 5-year overall survival of up to 80%, patients with HPV-positive OPSCC have a better prognosis compared to patients with HPV-negative OPSCC, where survival rates are between 40 and 50%.

[Effects of the SARS-CoV­2 pandemic on the otolaryngology university hospitals in the field of research, student teaching and specialist training]. / Auswirkungen der SARS-CoV­2-Pandemie auf die universitäre Hals-Nasen-Ohren-Heilkunde im Bereich der Forschung, Lehre und Weiterbildung.

BACKGROUND: From spring 2020, SARS-CoV­2 began to spread worldwide, with what is now known as the first wave of the pandemic, starting in March 2020. This resulted in restructuring and shift of resources at many hospitals. The aim of our work was to detect the effects of the pandemic on the german Oto-Rhino-Laryngology (ORL) university hospitals in terms of research, student teaching and further specialist training. MATERIAL AND METHODS: The chairmen of the 39 ORL university hospitals in Germany were asked about the effects of the pandemic on research, student teaching and ORL specialist training (residency) in the period from March to April 2020 using a structured online survey. RESULTS: All 39 chairmen took part in the survey. Of these, 74.4% (29/39) stated that their research activities had deteriorated as a result of the pandemic. In 61.5% (24/39) pandemic-related research issues were addressed. All hospitals reported a restriction for in-house teaching and 97.5% (38/39) introduced new digital teaching methods. During the observation period, 74.4% of the chairmen did not see ORL specialist training (residency)at risk. CONCLUSION: Our results provide an insight into the heterogeneous effects of the pandemic. The fast processing of pandemic-related research topics and the introduction of innovative digital concepts for student teaching impressively demonstrates the great innovative potential and the ability of the ORL university hospitals to react quickly in order to maintain their tasks in research, student teaching and ORL specialist training in the best possible way even during the pandemic.

[Tumor microenvironment in salivary gland carcinomas: Consequences for new therapeutic concepts]. / Das Tumormikromilieu bei Speicheldrüsenkarzinomen ­ mögliche Konsequenzen für neue Therapiekonzepte.

INTRODUCTION: Salivary gland carcinomas (SGCs) are rare tumors which represent a challenge for diagnosis and therapy due to their histological diversity and the different disease courses depending on the respective subtype. Little is known about the composition of the tumor microenvironment in SGCs. A more comprehensive understanding of the relevant molecular changes and immunological processes of the tumor and surrounding stroma could help to improve therapeutic efficiency, for example by adjuvant immunomodulation. METHODS: This manuscript highlights recent studies analyzing the composition of the tumor microenvironment in salivary gland carcinomas. RESULTS: The tumor microenvironment displays a significant diversity in the composition of immune cells among different tumor entities. In one third of the SGCs, an expression of cell surface molecule LAG3 on tumor infiltrating lymphocytes could be observed. LAG3-similar to CTLA­4 and PD-1-inhibits cellular proliferation, activation, and homeostasis of antitumor-effective T cells. Especially, prognostically less favorable entities such as salivary duct carcinomas and adenocarcinomas NOS (not otherwise specified) yielded higher expressions. CONCLUSIONS: LAG3 is particularly detectable in aggressive entities and advanced tumors. Hence, LAG3 inhibition poses a potential targeted therapy for advanced and metastatic SGCs.

[Effects of the SARS-CoV-2 pandemic on the otorhinolaryngology university hospitals in the field of medical care]. / Auswirkungen der SARS-CoV-2-Pandemie auf die universitäre Hals-Nasen-Ohrenheilkunde im Bereich der Krankenversorgung.

INTRODUCTION: Since December 2019, the SARS-CoV-2 virus has been rapidly spreading worldwide. In Germany, an exponential increase in the number of infections was registered at the beginning of March 2020 and led to a call of the Ministry of Health to create more capacity for intensive medical treatment in hospitals. The aim of the present study was to determine the effects of the SARS-CoV-2 pandemic on Oto-Rhino-Laryngology (ORL) university hospitals regarding patient care. MATERIALS AND METHODS: An online survey was sent out to all chairmen of the 39 ORL university hospitals in Germany. The answers to the questions referred to the defined period from March 15th to April 15th 2020 and were carried out using the online survey tool "SurveyMonkey". 87 questions focused on general information, health care, and structural effects in the respective institution. RESULTS: All chairmen of the 39 university hospitals in Germany participated in the survey. The collected data prove the considerable impact on organizational, structural and medical aspects of patient care. For example, the surveyed clinics reported a decrease in outpatient cases by 73.8 % to 26.2 ±â€Š14.2 % and in surgical treatments by 65.9 % to 34.1 ±â€Š13.9 %. In contrast, emergency treatment remained unchanged or even increased in 80 % of the facilities and surgical treatment of emergency patients remained unchanged or even increased in more than 90 %. Emergency outpatient and surgical treatment of patients was provided throughout the pandemic in all facilities. In total, about 35 000 outpatients and about 12 000 surgical cases were postponed. As a result of the acute structural changes, the potential danger of falling below current treatment standards was seen in individual areas of patient care. DISCUSSION: The assessment of the impact of the SARS-CoV-2 pandemic is heterogeneous. The majority of the chairmen are critically aware of the risk of falling below current medical treatment standards or guidelines. In the phase of an exponential increase in the number of infections, significant changes in treatment processes had to be accepted for understandable reasons. However, with the currently significantly reduced number of infections, falling below treatment standards and guidelines should not be allowed to remain constant and tolerated. SUMMARY: This study shows a differentiated picture with regard to the effects of the SARS-CoV-2 pandemic on outpatient, inpatient and operative patient care at the ORL university hospitals in Germany and illustrates the importance of these institutions for ensuring patient care during this critical phase.

Risk profiling based on p16 and HPV DNA more accurately predicts location of disease relapse in patients with oropharyngeal squamous cell carcinoma.

BACKGROUND: In the era of precision medicine and HPV-related oropharyngeal squamous cell carcinoma (OPSCC), it is relevant to assess the risk of not only survival, but also the risk of local, regional, or distant treatment failure. The UICC 8th edition uses the surrogate marker p16 to stratify for HPV association but discordance between p16 status and HPV association has been shown. The purpose of this study was to develop a prognostic model to predict the risk of local, regional, and distant metastases and non-cancer-related death for patients with OPSCC, test the prognostic relevance of adding HPV DNA and p16 status, and validate the findings in an independent external dataset. PATIENTS AND METHODS: Consecutive patients diagnosed with OPSCC and treated with curative radiotherapy with or without cisplatin in eastern Denmark from 2000 to 2014 were included. Characteristics included age, gender, TNM stage, smoking habits, performance status, and HPV status assessed with p16 and HPV DNA. The information was used to develop a prognostic model for first site of failure with four competing events: recurrence in T-, N-, and M-site, and death with no evidence of disease. RESULTS: Overall 1243 patients were eligible for the analysis. A prognostic model with the four events was developed and externally validated in an independent dataset with a heterogeneously treated patient population from another institution. The individual prognostication from the competing risk analysis is displayed in a user friendly online tool (https://rasmussen.shinyapps.io/OPSCCmodelHPV_p16/). Replacing p16 status with the combined variable HPV/p16 status influenced the HR and patients with HPV-/p16+ had significantly higher HR of M-site recurrence than HPV+/p16+ with a HR = 2.56; CI [1.30; 5.02]; P = 0.006 (P = 0.013 in the validation cohort). CONCLUSION: Patients with HPV-/p16+ have significantly higher risk of M-site recurrence and could potentially be relevant candidates for clinical trials testing systemic treatments in combination with conventional treatments.

[Update on HPV-associated head and neck cancer-highlights from the 2019 ASCO Annual Meeting]. / Update zu HPV-assoziierten Kopf-Hals-Karzinomen ­ Highlights der ASCO-Jahrestagung 2019.

At this year's Annual Meeting of the American Society for Clinical Oncology (ASCO), the keyword search "HPV-associated head and neck cancer" resulted in 920 hits-74% of the hits on human papillomavirus (HPV). This underlines the relevance of the topic. The spectrum ranged from validation and separation of the prognostic groups of patients with HPV-associated oropharyngeal carcinoma (OPSCC) according to TNM 8, to the characterization of new tumor markers and tumor mutational burden for possible de-escalation strategies to avoid toxicity of standard multimodal treatments. It has been shown that the separation of p16-positive OPSCC into Union for International Cancer Control (UICC) stages I and II with the current TNM 8 classification without further markers is not sufficiently successful to justify de-escalation strategies. Following publication of the results of the De-ESCALaTE- and RTOG-1016 trials in 2018, which confirm the current standard of care for p16-positive OPSCC, no further phase III studies on de-escalation were presented. In a presented prospective phase II study (NCT02281955), the radiotherapy dose was reduced to cumulative 60 Gy, whereby the simultaneous chemotherapy regimen with cisplatin 30 mg/m2 weekly is not standard of care and could be administered as an alternative to cisplatin cetuximab. Some work dealt with the oral and intestinal microbiota as prognostic markers or their treatment-related changes, particularly under immunotherapy. Modification seems to have a positive impact on the success of therapy. However, robust data are still lacking for the various modified treatments for HPV-associated OPSCC, which are needed before their implementation in daily practice.

Induction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy-final results of the larynx organ preservation trial DeLOS-II.

Background: The German multicenter randomized phase II larynx organ preservation (LOP) trial DeLOS-II was carried out to prove the hypothesis that cetuximab (E) added to induction chemotherapy (IC) and radiotherapy improves laryngectomy-free survival (LFS; survival with preserved larynx) in locally advanced laryngeal/hypopharyngeal cancer (LHSCC). Patients and methods: Treatment-naïve patients with stage III/IV LHSCC amenable to total laryngectomy (TL) were randomized to three cycles IC with TPF [docetaxel (T) and cisplatin (P) 75 mg/m2/day 1, 5-FU (F) 750 mg/m2/day days 1-5] followed by radiotherapy (69.6 Gy) without (A) or with (B) standard dose cetuximab for 16 weeks throughout IC and radiotherapy (TPFE). Response to first IC-cycle (IC-1) with ≥30% endoscopically estimated tumor surface shrinkage (ETSS) was used to define early responders; early salvage TL was recommended to non-responders. The primary objective was 24 months LFS above 35% in arm B. Results: Of 180 patients randomized (July 2007 to September 2012), 173 fulfilled eligibility criteria (A/B: larynx 44/42, hypopharynx 41/46). Because of 4 therapy-related deaths among the first 64 randomized patients, 5-FU was omitted from IC in the subsequent 112 patients reducing further fatal toxicities. Thus, IC was TPF in 61 patients and TP in 112 patients, respectively. The primary objective (24 months LFS above 35%) was equally met by arms A (40/85, 47.1%) as well as B (41/88, 46.6%). One hundred and twenty-three early responders completed IC+RT; their overall response rates (TPF/TP) were 94.7%/87.2% in A versus 80%/86.0% in B. The 24 months overall survival (OS) rates were 68.2% and 69.3%. Conclusions: Despite being accompanied by an elevated frequency in adverse events, the IC with TPF/TP plus cetuximab was feasible but showed no superiority to IC with TPF/TP regarding LFS and OS at 24 months. Both early response and 24 months LFS compare very well to previous LOP trials and recommend effective treatment selection and stratification by ETSS. Clinical trial information: NCT00508664.

Highlights from the Second International Symposium on HPV infection in head and neck cancer.

The Second International Symposium on HPV Infection in Head and Neck Cancer was held on 3rd-4th November 2016 in Leipzig, Germany. The meeting brought together researchers and clinicians to share the latest knowledge on HPV infection in head and neck cancer and to join active and constructive scientific discussions. This report summarizes the major themes discussed during the symposium.

Patient's perspective on long-term complications after superficial parotidectomy for benign lesions: Prospective analysis of a 2-year follow-up.

OBJECTIVE: Evaluation of patients' perspective on long-term complications after superficial parotidectomy for benign lesions. DESIGN: A prospective nonrandomized controlled multicenter study. SETTING: Three university-based tertiary referral centers (Departments of Otorhinolaryngology of Cologne, Jena and Giessen; all in Germany). PARTICIPANTS: 130 adult patients, who underwent a primary superficial parotidectomy for benign tumors of the parotid gland, were consecutively included from 09/2010 to 05/2012. 61 patients completed every follow-up examination. MAIN OUTCOME MEASURES: Complications were evaluated using the validated German-language questionnaire Parotidectomy Outcome Inventory 8 at six, 12 and 24 months after surgery. Pain intensity was assessed on a numeric rating scale (NRS) at each follow-up visit. RESULTS: At 6 months after surgery, 90% characterized hypoesthesia as the most disturbing problem, followed by fear of revision surgery (57%) and scar (56%). Facial palsy (14%) posed the minor problem. Hypoesthesia improved significantly during the follow-up period (all P < .05), but still posed a problem for 78% of the patients after 2 years. Pain, which initially bothered 53% of the patients, significantly decreased, whereas impairment due to Frey's syndrome significantly increased during the follow-up (6 vs 24 months; P = .002 and P = .001, respectively). Scar, substance loss, xerostomia, facial palsy, and anxiety affected patients with unvarying severity during the 2 years (all P > .05). CONCLUSIONS: From patients' perspective, sensation loss posed the major subjective problem after superficial parotidectomy. Appearance of the scar, and fear of revision surgery impaired more than 50% of the patients in their daily life without significant improvement during the 2 years postoperatively. Although superficial parotidectomy is a highly standardized and safe procedure, limited parotidectomy for proven benign parotid salivary gland neoplasms is more likely to result in patients with minimal or no displeasing complications.