• Abstract
• 1. Introduction
• 2. Quality-Improving Conditions in Oncology
• 2.1. National cancer plan
• 2.2. Cancer registry
• 2.3. Guidelines
• 3. Quality Indicators in Head and Neck Oncology
• 3.1 Quality indicators of AWMF guidelines on oral cavity and laryngeal cancer
• 3.2 Other quality indicators of head and neck oncology
• 4. Certification of Head and Neck Cancer Centers
• 4.1 Volume effect in head and neck oncology
• 4.1.1 Hospital volume
• 4.1.2 Quality assurance of surgery
• 4.2. Optimized therapy decisions based on interdisciplinary tumor boards
• 5. Patient-Orientation as Quality Criterion
• 5.1 Patient information and communication
• 5.2 Right to obtain medical second opinion
• 5.3 Patient-oriented process design
• 5.4 Improvement of psychooncologic care
• 5.5 Patient-Reported Outcome (PRO)
• 6. Increase of the Outcome Quality by Personalized Medicine
• 7. Quality in Trials on Head and Neck Oncology
• 8. Quality of Follow-up in Head and Neck Oncology
• 9. Conclusion and Outlook
• Literatur

Abstract

A professionally qualified, patient- and demand-oriented, economic, high-quality care of patients with head and neck cancer is a challenge. Quality optimization in German head and neck oncology is based on quality-enhancing framework conditions such as the National Cancer Plan, the expansion of clinical cancer registries and the existence of evidence-based guidelines that were drawn up as part of the “Oncology Guidelines Program” initiated in 2008 (S3-guidelines for oral cavity and larynx cancer). There are currently 56 certified head and neck cancer centres in Germany with the aim of objectifiably increasing the quality of treatment and improving the outcomes of patients. Various quality indicators have been developed, there are programs for quality assurance of therapy and within studies. The aim of this review is to present quality standards in head and neck oncology.

Abstract

A professionally qualified, patient- and demand-oriented, economic, high-quality care of patients with head and neck cancer is a challenge. Quality optimization in German head and neck oncology is based on quality-enhancing framework conditions such as the National Cancer Plan, the expansion of clinical cancer registries and the existence of evidence-based guidelines that were drawn up as part of the “Oncology Guidelines Program” initiated in 2008 (S3-guidelines for oral cavity and larynx cancer). There are currently 56 certified head and neck cancer centres in Germany with the aim of objectifiably increasing the quality of treatment and improving the outcomes of patients. Various quality indicators have been developed, there are programs for quality assurance of therapy and within studies. The aim of this review is to present quality standards in head and neck oncology.

1. Introduction

There are different definitions in the literature for the term of quality. It is widely distributed to consider quality as the degree of conformance between defined requirements of quality criteria and their fulfilment. The DIN EN ISO 8402 defines quality as the set of characteristics (and feature values) of a unit in terms of its suitability to meet specified and anticipated needs. In 1990, the American Institute of Medicine of the National Academy of Sciences presented the following definition of quality for healthcare: “Quality of care is the degree to which health services for individuals and populations increase the likelihood of desired health outcomes and are consistent with current professional knowledge” [1]. For oncology, this aspect is of particular importance. Like other industrial nations, Germany has to cope with increasing challenges despite all progress because the number of newly diagnosed cancer diseases has nearly doubled since 1970, and cancer is the second most frequent cause of death [2]. Currently about 4 million people live in Germany who suffer or suffered from cancer. In future, the relevance of cancer diseases will further increase because of demographic aging. In 2014, 476 000 cancer diseases were newly diagnosed in Germany; carcinomas of the oral cavity and the pharynx were the ninth most frequent tumor entity in men with 12 830 newly diagnosed patients (prognosis for 2018: 13 700 new diagnoses), while it was the 15^th most frequent one in women in Germany. The relative 5-year survival rate amounted to 59% in female and 48% in male patients [3]. In cases of laryngeal carcinomas, the disease and mortality rates in men decrease and are currently stable in women. In 2014, 3 500 laryngeal carcinomas were newly diagnosed; the 5-year survival rate was balanced with 63% in male and 64% in female patients [4]. In the last years, the therapeutic concepts for head and neck tumors developed enormously. Transoral or open surgery and radio(chemo)therapy are still the mainstay of primary treatment. However, due to new drug-related therapeutic concepts such as immunotherapy with checkpoint inhibitors the treatment of patients suffering from squamous cell carcinomas of the head and neck becomes more and more complex. Even for experienced specialists it is difficult to keep an overview of new developments. The objective of high-quality, patient-oriented oncological care is to provide head and neck cancer patients with an appropriate therapy that corresponds to the current state of research. Hereby, different dimensions of medical care quality have to be distinguished: structural quality, process quality, and outcome quality [5]. While the structural quality refers to structural conditions, the process quality focuses on the functioning of processes. A high quality of the outcome is met when a possible treatment objective is actually achieved. In general, the outcome quality has the highest priority, while a good result depends on the process quality and a good process quality results from the existing structures. However, it is most difficult to measure the outcome quality because different influencing factors such as age and comorbidities are relevant. So the structural and process quality are more frequently analyzed since they can usually be measured more easily and are less subject to influencing factors than the outcome quality. Furthermore, the quality of healthcare has possibly different levels of significance for patients and their relatives and the various healthcare service providers. In addition, good quality depends on several factors such as for example the infrastructure, quality and motivated staff, patient-centered processes, and quality-improving legal conditions. Due to progresses made in oncologic diagnostics and therapy, quality is automatically subject to permanent change and thus has to be considered as dynamic. The aim of this article is to describe quality standards in head and neck oncology.

2. Quality-Improving Conditions in Oncology

The service providers in the German healthcare system are obliged to quality assurance (§ 134 ff SGB V). Furthermore, legislation defines reductions of the remuneration for service providers that do not fulfil their obligation of quality assurance and additional payment as incentive for performing quality assuring measures. The various requirements of assuring the quality of healthcare provision also include §5 of the professional code of conduct for physicians in Germany, i. e. physicians are obliged to participate in measures of medical quality assurance introduced by the Federal Medical Chambers and to provide necessary information in this regard [6]. In the context of quality assurance, external and internal procedures must be differentiated. External procedures of quality assurance in oncology include official requirements such as the national cancer plan [7], cancer registries, and oncological certifications. The internal oncological quality assurance encompasses general measures such as the application of standard operating procedures (SOP) and treatment pathways as well as interdisciplinary tumor boards. As examples for quality-improving conditions in head and neck oncology, the national cancer plan, the implementation of clinical cancer registries that provides an important data basis for quality assurance and improvement, and the existing S3-guidelines in Germany will be illustrated in the following chapters.

2.1. National cancer plan

The national cancer plan (Nationaler Krebsplan) [7] was initiated in 2008 as Council conclusion of the European Parliament and recommendation of the World Health Organization with the objective to improve the fight against cancer by effective and coordinated action. It is a long-term coordination and cooperation program that was started by the Federal Ministry for Health in cooperation with the German Cancer Society (Deutsche Krebsgesellschaft, DKG), the German Cancer Aid (Deutsche Krebshilfe), and the Workgroup of German Cancer Centers (Arbeitsgemeinschaft Deutscher Tumorzentren). The focuses of the national cancer plan are placed on four fields of action with 13 objectives. The first field of action contains the development of early detection of cancer. The objectives are the increase of the utilization of screening programs of which the benefit is confirmed and that are offered by the statutory health insurances, the adherence to the European recommendation of systematic population-based screening programs as well as the evaluation of the cancer screening programs with regard to their benefit with involvement of the epidemiologic federal cancer registry.

The second field of action consists of a further development of the oncological treatment structures and quality assurance. The basis is that all cancer patients, regardless of their age, gender, background, place of residence, and health insurance status, receive high-quality care. Further objectives include the definition of standardized concepts and terminology for quality assurance, of quality improvement, and of certification of oncological treatment institutions. In addition, for all frequently diagnosed tumor entities evidence-based treatment guidelines should be developed of highest methodical degree (so-called S3-guidelines) that are implemented by oncological treatment institutions. This also includes assuring the suitable distribution and application of guidelines and the evaluation of the consequences of guideline application by critically analyzing the healthcare data in regional and national quality conferences. Another objective is the assurance of cross-sector, integrated oncological care with improvement of the interdisciplinary cooperation (e. g. tumor boards) and cross-sector and interdisciplinary networking of oncological care as well as the involvement of self-aid groups in the treatment. Further, the existence of a relevant oncological quality reporting for service providers, decision makers, and patients should be assured. This includes the nation-wide establishing of clinical cancer registries for assessment of the quality of care of all cancer patients, strengthening the networks of regional clinical cancer registries as well as clinical and epidemiological cancer registries, involving them in cross-sector quality assurance based on § 137 SGB V, the re-transmission of the data to all involved service providers in form of structured critical outcome assessments as well as the transparent illustration of the results for hospitals, physicians, patients, and the public. Additionally, all cancer patients should receive suitable psycho-oncological care, if needed.

The third field of action regulates the assurance of an efficient oncological treatment to which all patients should get fair and rapid access. This includes the promotion of clinical verification of oncological treatment, the assurance of rapid translation of new therapeutic options from basic research into clinical application, the assurance of evidence-based and cost-effective care, and the sustainable assurance of the financing of medically necessary, expensive oncological medication.

The fourth field of action includes strengthening of the patient orientation, whereby the objectives define the active involvement of patients into decision making about medical measures, the improvement of communication skills of the service providers, the strengthening of patient literacy as well as the presence of low-threshold, target-group oriented and quality assuring information or consultation and support offers.

2.2. Cancer registry

One important result of the national cancer plan is the act on development of early cancer detection and quality assurance by clinical cancer registries (Krebsfrüherkennungs- und -registergesetz, KFRG) issued on April 9, 2013. The KFRG obliges all Federal States to implement regional clinical cancer registries that assess all relevant data occurring in the course of oncological disease and its treatment. In contrast to clinical cancer registration, the epidemiological data collection has a long tradition in Germany. Already in 1926, a population-based assessment of newly diagnosed oncological diseases and deaths was performed [8], this registry, however, could not survive the period of National Socialism. Based on a legal reporting obligation since 1952/53, the cancer registry of the German Democratic Republic documented epidemiological data. In 1993, the entire database was included in the joint cancer registry of the new Federal States and Berlin (Gemeinsames Krebsregister der neuen Bundesländer und Berlin, GKR) [9]. The oldest cancer registry of the “old” Federal States is the cancer registry of the Saarland that collects patient-related data since 1967 [10]. The first federal act for cancer registries of 1995, obliged all Federal States to establish epidemiological cancer registries until December 31, 1999. However, since no general reporting obligation was introduced at that time, the implementation was not performed nation-wide. Since 2006, a legal basis exists in the Federal States for the nation-wide epidemiological cancer registration. The federal act on cancer registry data that became effective in 2009, shall make reliable nation-wide data on cancer diseases available. The residence-related data of the single epidemiological cancer registries are reported to the center of cancer registry data at the Robert Koch Institute. From there, for example data were transmitted to EUROCARE-5 which is the largest trial on population-related survival of cancer patients in Europe [11]. In 2013, the KFRG became effective. In contrast to epidemiological cancer registries that contain mainly diagnoses and data regarding the incidence and mortality, clinical cancer registries may assess data on diagnostics, therapies, and courses as for example complications, recurrences, and secondary tumors in a standardized way. In this way, the assessment of age-, gender- and group-related effectiveness of therapies and the treatment quality is allowed. Thus, clinical cancer registries contribute of guideline-conform healthcare. Due to the KFRG, the legal and financial preconditions for the establishment and maintenance of nation-wide clinical cancer registries in Germany were implemented for the first time. A reporting obligation for physicians and hospitals is the basic condition of the functioning of clinical cancer registries. On the other hand, the feedback of current survival and progress data to the treating physicians and hospitals may contribute to quality improvement. The clinical cancer registries receive a legally defined lump sum per registered case, the treating physicians that transmit their patient data to a clinical cancer registry receive a reporting remuneration.

The starting point for the KFRG was the national cancer plan that provided the framework conditions for the development of early cancer detection and the nationwide implementation of clinical cancer registries in Germany. In this way, a systematic and standardized data collection shall be assured and the oncologic quality reporting and thus the oncologic care shall be strengthened. By means of cancer registries related to the outcome quality, survival times, disease-free times, and the quality of life may be evaluated, in relation to the process quality the adherence to guidelines and therapy standards are assessed, and related to the structural quality for example the incidence of different therapy procedures is checked. To complete guidelines and certification programs, registries may become an important instrument of quality assurance in oncologic treatment [2]. Unfortunately, the implementation is difficult because of different structural/historical issues in the Federal States and a central reporting office that might actually collect and evaluate nationwide data is currently not yet planned. In parallel, cancer centers have disappeared in many places that up to now assumed the task of cancer registration. The independence of the registries as autonomous institutions promoted by the KFRG only makes sense if they cooperate on one hand with the tumor centers and on the other hand network nationwide via the State coordination offices. It remains to be seen if the KFRG finally creates isolated reporting offices and thus setback, or if the integration in patient care and thus quality improvement will be successfully achieved.

A second objective of the KFRG is to sustainably improve the early detection of cancer in Germany. Based on European guidelines, the structure and quality of screening programs should be optimized. Currently, there are organized early detection programs for colon and cervical carcinomas, until now programs for the screening of head and neck cancer have not been established.

2.3. Guidelines

In order to assure high quality of oncological care, therapy decisions should be made based on the principles of evidence-based medicine. These principles combine three factors: best available scientific knowledge, medical experience, and the patients’ ideals [12]. Guidelines summarize the evidence, evaluate it, and conclude instructions; thus they are a relevant instrument to promote quality and transparency in oncological treatment. Therefore, diagnostics and therapy of head and neck cancer should be performed according to nationally and internationally acknowledged guidelines. The guidelines of the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO), and the European Society of Medical Oncology (ESMO) are internationally accepted [13] [14] [15] [16] [17] [18]. Regarding national guidelines on head and neck cancer in Germany, there are currently the AWMF S3-guidelines on cancer of the oral cavity (which is currently revised) [19] and laryngeal cancer that was finalized on January 31, 2019, and is effective until January 30, 2024 [20], a S3-guideline on oropharyngeal cancer is planned. The generation of the AWMF S3-guidelines is performed in a methodically defined evidence and consensus procedure in the context of the guideline program on oncology that was initiated in February 2008. It is the case of a cooperation of the Workgroup of scientific medical societies (Arbeitsgemeinschaft wissenschaftlicher medizinischer Fachgesellschaften, AWMF), the German Cancer Society (Deutsche Krebsgesellschaft, DKG), and the German Cancer Aid (Deutsche Krebshilfe) aiming at the development and the application of scientifically sound and feasible guidelines in oncology. The guideline program on oncology encompasses guidelines for diagnostics, therapy, and aftercare of frequently observed cancer diseases, but also guidelines for more complex healthcare topics that are also relevant for head and neck oncology such as for example psycho-oncology or palliative medicine as well as prevention and early detection of cancer diseases [21].

Currently, the AWMF guidelines have a relatively long validity duration with 5 years. Earlier updates and amendments of the guidelines are possible. After five years, about 50% of the guideline recommendations are still applicable, in particular changes of therapy recommendations are frequent due to new evidence. It could be shown that recommendations based on several randomized trials have a significantly longer applicability than expert opinions. On the average, the up-to-dateness of the 20 published guidelines of the oncology guideline program amounts to 2.3 years (median: 1.6 years) [22]. In order to always reflect the current evidence, living guidelines would be optimal, i. e. a continuous checkup and actualization of guidelines [23]. This would assure that the guidelines are permanent up-to-date, however, it would also mean immense time-consuming and organizational efforts. On the other hand, a better up-to-dateness of the guidelines would clearly increase their acceptance, also because the topicality of the guidelines is a central problem of most guidelines due to the time-intensive generation process. As an example, the guideline on laryngeal cancer is mentioned; its kick-off for creation took place in Berlin on June 10, 2014 and it was finally published in January 2019.

Scientific investigations could show that guidelines may improve the process and outcome quality of patient care [24]. The crucial aspect is an adherence to the guidelines. Swegal et al. [25] revealed in a population of 1721 patients with laryngeal cancer that the treatment according NCCN guidelines was associated with a better survival. This thesis is confirmed by other trials [26] [27].

Since March 2019, the guidelines of the DKG are also available as app [28] which facilitates the nationwide application in daily routine. The nationwide implementation of the S3-guidelines was an important reason for the development of the certification system. In the context of the guideline program on oncology, quality indicators are defined for all topics of the guidelines that are included in the parameter lists of the DKG certified centers.

3. Quality Indicators in Head and Neck Oncology

Quality indicators are precisely defined criteria that should allow a differentiation into good and poor medical quality. They have to correspond to the current state of medical care and thus have to be continuously developed. The definition of medical quality criteria is challenging and optimally it is performed by the medical societies with cooperation of all parties involved, i. e. for example patient representatives. Quality criteria should display the best available evidence. McGlynn defined the following criteria for quality indicators: relevance and benefit for quality improvement (significance for the healthcare system), scientific character and differentiation capability (reliability, validity, sensitivity, specificity) as well as the feasibility and practicability (comprehensibility for patients and treating professionals, assessment efforts) [29]. Meanwhile, quality indicators belong to the most important evaluation instruments in oncology; they reveal the quality, but they are no direct measure for the quality [30]. They may refer to different areas, e. g. the implementation of guideline-based therapies (e. g. postoperative radio(chemo)therapy in cases of specific indications), the rate of undesired events (e. g. number of revision surgeries), or the implementation of new structures (e. g. pretherapeutic tumor board presentations).

3.1 Quality indicators of AWMF guidelines on oral cavity and laryngeal cancer

The quality indicators that are currently assessed in the context of oncologic certification are taken from the AWMF guideline on cancer of the oral cavity and larynx and refer mainly to aspects of structural quality and partly also of process quality, while nearly no requirements are made in terms of the outcome quality (e. g. survival, patient satisfaction). The bases for the definition of quality indicators in the context of AWMF guidelines were all strong recommendations (recommendation level A) of the guidelines as well as a research for existing national and international quality indicators [20]. The S3-guideline on carcinomas of the oral cavity mentions 10 quality indicators with respective target values ([Table 1]) [19]; the current guideline on laryngeal cancer includes 6 quality indicators with respective target values ([Table 2]) [2]. In addition to the 6 derived quality indicators, the S3-guideline on laryngeal cancer identified the time between surgery and the end of radiotherapy as area with improvement potential. Since the basic recommendation was classified as “should” according to the methods of the guideline program, it could not be used for the deduction of a quality indicator. Instead it was recommended that a parameter was introduced for the certification commission of head and neck cancer centers (numerator: number of patients with finalized radiotherapy within 77 days; denominator: all patients with first diagnosis of laryngeal cancer and postoperative radiotherapy), which was realized. Additionally, the proposal was made that a nationwide evaluation should be established via the cancer registries that depicts the time from surgery until the end of radiotherapy [20]. The advantage of integrating the quality indicators derived from the S3-guidelines in the assessment catalogue of head and neck cancer centers is that the implementation of the guideline contents may be verified in the context of audit procedures.

3.2 Other quality indicators of head and neck oncology

In the literature, an unmanageable number of different quality indicators is found, among them organ- or indication-specific indicators (e. g. functional integrity after radiotherapy of the larynx), but also cross-section indicators that may be applied in every type of cancer (e. g. the time between diagnosis and start/end of therapy). The quality indicators may include the environment where treatment is performed (indicators of structural quality), how operative standards are observed (indicators of process quality), and the outcome that is achieved for the patients (indicators of outcome quality). Structural quality indicators are for example the qualification of the staff, the presence of the technical infrastructure, a functioning organization and administration, and the possibility of an interdisciplinary and multimodal treatment by cooperating disciplines. Process quality indicators mainly assess the diagnostic procedures (adequate clinical/pathological staging) and therapy (adequate surgical/radiotherapeutic procedure, postoperative/posttherapeutic complication management, guideline-based multimodal therapy). The process quality indicators can be improved by standard operating procedures (SOPs) that are obligatory for oncological centers of excellence. SOPs are most current concrete diagnostic and therapeutic instructions that combine evidence-based guidelines, current medial knowledge, and local particularities [31] [32]. The most important indicator in head and neck oncology as measure for the effectiveness and quality of care, however, is the outcome, i. e. survival, recurrence rate, posttherapeutic function, and quality of life. An overview of different quality indicators suggested in the literature is given in [Table 3].

A large analysis regarding the observance of five defined quality indicators was performed by Cramer et al. [33] at the University of Chicago in a population of 76 853 patients of the National Cancer Data Base who had undergone surgery for head and neck cancer from 2004–2014. The investigated parameters included R0 resection, lymph node yield from neck dissection of >18, adjuvant irradiation or radiochemotherapy if indicated, start of adjuvant therapy within 6 weeks after surgery as well as overall quality. Regarding the quality parameters, it could be shown that R0 resection was found in 80%, in 73.1% of the patients a lymph node yield of >18 was achieved, 69% of the patients received adjuvant irradiation and 42.6% received adjuvant chemotherapy if indicated. In only 44.5% of the patients, the adjuvant therapy was started within 6 weeks. All parameters were associated with a reduced mortality risk. Regarding R0 resection, the hazard ratio (HR) amounted to 0.73 (95% confidence interval (CI): 0.71–0.76), regarding the lymph node yield of >18 it was 0.93 (95% CI: 0.89–0.96), concerning adjuvant irradiation it amounted to 0.67 (95% CI: 0.64–0.70), regarding adjuvant chemotherapy to 0.84 (95% CI: 0.79–0.88), and for the start of adjuvant therapy within 6 weeks it was 0.92 (95% CI: 9.80–0.96). The average overall quality factor for patients with these quality parameters amounted to 70.7%. The overall quality of care increased in the course of the time from an average of 68.6% in 2004 and 2005 to 71.3% in 2012–2014 (p<0.001). Patients who received high-quality care suffered more frequently from laryngeal cancer or were treated in large or academic hospitals. Patients received more rarely high-quality treatment as of an age of 75 years, many comorbidities, diagnosis of oropharyngeal cancer, higher T or N stage, extracapsular spread, HPV positivity, or statutory health insurance. Patients who received high-quality treatment had a mortality risk reduced by 19% (HR: 0.81; 95% CI: 0.79–0.83) and a median survival of 10.2 vs. 7.5 years in the group without high-quality care. Remarkably, the most relevant variable that was associated with high-quality care was the treatment in a high-volume center. In the study, 90% of the hospitals treated less than 160 cases over a period of 10 years and were thus identified as low-volume centers [33]. The correlation of quality and high-volume hospitals will also be discussed in Chapter 4.1.1.

4. Certification of Head and Neck Cancer Centers

The certification system is an integral part of the quality cycle in oncology that was determined by the national cancer plan [34]. With the aim of assuring the best possible treatment of all cancer patients in certified institutions a three-step model of oncological care is described by the national cancer plan ([Fig. 1]) [7]. The three-step model defines the different tasks of the certified centers, and the clinical treatment is performed on the different levels based on the same requirements. The basis of the three-step model of oncological treatment are organ cancer centers that shall assure a possibly nationwide therapy of the most frequent tumor entities according to the guidelines. The oncological centers are formed by merging different organ-specific organ cancer centers and also have the expertise for rarer tumors. Beside clinical care, the task of comprehensive cancer centers (CCC) is oncological top-level research. Currently, 13 comprehensive cancer centers are supported by the German Cancer Aid with 750 000 Euro per year and center. The CCC shall develop care structures and processes and foster oncology by innovative research so that all cancer patients may benefit.

Currently DKG-certified centers are established in more than 420 German hospitals; in addition to the German sites, there are DKG-certified centers in other European countries [35]. Currently, about 40% of all patients in Germany with oncological diagnosis are treated in a DKG-certified center [36]. For single tumor entities, this rate is even higher. In 2016, 76% of the patients suffering from breast cancer and 55% of the patients with malignant melanoma were treated in DKG-certified centers [37]. Seven years after the first certifications of head and neck cancer centers in Germany in 2011, meanwhile 56 institutions are certified as head and neck cancer centers (status: December 31, 2018). In 2017, a total of 8 203 primary cases were treated in these certified head and neck cancer centers. This was an average of 146.4 primary cases per site [38]. The development of certified head and neck cancer centers from 2011–2018 as well as the primary cases treated in the centers is displayed in [Figs. 2] and [3]. While in 2013 only 13.1% of the patients newly diagnosed with head and neck cancer were treated in a certified center, there were already 28.5% in 2015 [39].

The basis of the certification system is the presence of evidence-based guidelines. The certification commission called by the DKG defines the requirements for certification based on these guidelines and is thus the actual legislative organ for the centers. These requirements generally concern the structural, process, and outcome quality. A total of 34 specific societies, associations and groups are involved in the certification commissions for head and neck cancer centers so that the composition, similar to guideline commissions, is multiprofessional and interdisciplinary and also patient representatives are involved. The company of OnkoZert is an independent institute which is entitled by the DKG to perform audits, to organize schoolings of experts, data management, and generation of benchmark reports. OnkoZert does not contribute to the establishment of requirements and the contents of the assessment catalogue. Auditors that are independent from the commission check the hospitals if they meet the requirements determined for certification. Finally, a panel decides about certification based on the recommendation by experts. This panel is constituted by three experienced experts. Since January 1, 2018, the certification of head and neck cancer centers is possible also without a certified oncological center if certain structures are present (e. g. department of hematology and oncology with beds, at least one certified center at the hospital that assures the cooperation in cross-sectional fields, competence of cross-sectional disciplines such as palliative medicine and psycho-oncology). Beforehand, a structural evaluation is performed that is relevant for the approval of the certification procedure [40].

The healthcare quality of certified centers is assessed by means of defined quality indicators (see Chapter 3.1) and parameters. It is made transparent by publication of tumor-specific annual reports that finalize the oncological quality cycle. The certified center shows to patients and referring practices that it meets the requirements of the DKG and expresses its commitment to high quality standards. Of course, a high quality may also be found without certification, but certification may confirm it publicly. By assessing and publishing quality parameters, a further development of the requirements can be performed and processes in the centers may be started in order to improve the structures. Currently, it is possible to reveal that head and neck cancer centers realize guideline-conform patient care. This becomes obvious by the adherence to various parameters [38]. The objective of the certification system is not only the assurance of guideline-based treatment, but also the promotion of interdisciplinary and multiprofessional cooperation. The centers have to prove the existence of a network of treating professionals from different disciplines and other medical professions that are interconnected based on cooperation contracts [41]. Beside otorhinolaryngology and maxillofacial surgery, the main treatment partners of the network include radiation oncology, internal oncology, pathology, and radiology. Further disciplines such as palliative medicine and nuclear medicine, and other professions such as psycho-oncology, social work, and physiotherapy have to be involved in the patient care of the center as well as cooperation with self-help groups and practicing physicians ([Fig. 4]). The certification parameters also include factors of interdisciplinarity and multiprofessionality such as psycho-oncological care and social-medical consultation. Furthermore, the conduction of joint quality cycles and educational measures has to be proven.

Additionally, the certification of cancer centers supports structured cancer documentation. The current annual report of the head and neck cancer centers shows that cancer documentation in German certified head and neck cancer centers follows different cancer documentation systems. The most frequently used system (19 centers [35%]) is the Giessen Cancer Documentation System (Giessener Tumordokumentationssystem, GTDS), followed by Credos (14.81%), c37.Cancer Center (12.96%), and ODSeasy/ODSeasyNet (12.96%) [38]. It is desirable to interconnect cancer documentation systems with the hospital software in order to avoid the currently often necessary double documentation. Integrated information systems that are tailored especially on the needs of medical experts may contribute to optimize the data management in head and neck oncology. A user-oriented design is relevant for detailed and intuitive support of healthcare professionals [42].

A further aim of certification is to make quality of the interdisciplinary care of cancer patients more transparent by means of the implementation of concrete data and parameters. The annual certification allows continuous assessment and control of these parameters. Every year, the data from the previous audit year are published containing the parameters of two years before. After analysis of the parameters, annual adaptations may be performed. One example in this context is revision surgery. In terms of revision surgery, the catalogue of requirements was adapted for 2018 and the rate of revision surgeries was increased from 10–15% because it became obvious that especially large centers had very high revision rates due to patients with advanced tumor stages or pre-treated patients, patients with significant comorbidities as well as a high percentage of microvascular flaps. Last, the median amounted to 9.1%, the previous target value of <10% could only be achieved by 63% of the sites [38].

The objective of quality assurance measures is an improvement of treatment outcomes. Currently, the survival as parameter of the outcome quality is not requested in German head and neck cancer centers. Up to now, an improved survival rate of the patients, similar to colorectal cancer centers, is not confirmed after certification of a head and neck cancer center. Therefore, the collection of hard data of the outcome quality, like overall survival, tumor-specific survival etc., should be included.

In summary, the advantage of certification is that treatment processes become transparent and are analyzed with regard to their efficiency and that precise instructions for procedures may be improved. The annually performed re-certification is motivation to optimize the processes [43]. Without any doubt, the certification is to confine the treatment sites based on objective criteria and thus to achieve higher case numbers with the meanwhile proven higher treatment professionality in the specific centers. It is obvious that a smaller hospital that is not able to encompass the required partners on site, especially in direct neighborhood to a well-established center, should not obtain a certificate based on adventurous networks.

4.1 Volume effect in head and neck oncology

4.1.1 Hospital volume

The fulfilling of minimum quantities is a core criterion in the context of certification by the DKG. For the first time in 1979, a report was published about the empirical relation between surgical treatment volume and mortality and the question of regionalization of surgeries came up [44]. In the following, a significant correlation between a decreasing perioperative mortality and an increasing hospital volume could be revealed for oncological surgeries of the lung, esophagus, stomach, colon, pancreas, kidney, and bladder [45] [46]. Numerous trials also confirmed a correlation between higher case numbers and better outcome for the surgical therapy of head and neck carcinomas [33] [47] [48] [49]. For example, an analysis of 11 160 surgically treated head and neck carcinomas based on the cancer registry of Florida shows that the treatment in a high-volume center (about 60 cases per year) is an independent predictor for survival (HR 1.25). The median survival amounted to 61 months in cases of treatment in high-volume centers, in intermediary-volume centers (about 21 cases per year) it was 52 months, and in low-volume centers (about 3 cases per year) 47 months (p<0.001). The survival advantage in high-volume centers could mainly be shown for tumors smaller than 3 cm and tumors of the larynx, pharynx, and the parotid gland [50].

For radiotherapy it also could be revealed that the expertise of a hospital in treating head and neck cancer had a significant impact on survival. A trial performed on behalf of the American Academy of Otolaryngology – Head and Neck Surgery Foundation could show for patients who received primary or adjuvant radiotherapy that the survival rates in specialized departments of academic cancer centers were significantly better in comparison to smaller community hospitals (academic: 5-year survival of 53.2% vs. community: 32.8%; p<0.001) [51]. Despite several differences between both types of institutions (more oropharyngeal carcinomas, more non-smokers, and significantly higher income of the patients in university hospitals) that might have led to bias, there were significant differences in the process quality like for example the conception of adjuvant therapy [51].

Overall, studies on head and neck carcinomas show a better patient selection in specialized centers with high case volumes. This could be confirmed by an analysis of 19,326 patients suffering from advanced laryngeal cancer [52]. Another trial with 969 patients with T4a laryngeal cancer could reveal that in hospitals with higher case numbers primary total laryngectomy was performed more frequently and that total laryngectomy was associated with a better median survival than primary radiochemotherapy (61 vs. 39 months of median survival) [53].

In the literature, two possible theories are distinguished for the high-volume effect: “practice makes perfect” and “selective referral” [54] [55]. The “practice makes perfect” hypothesis is based on the idea that increasing numbers of cases improve the outcome quality due to learning curve effects [54]. In this approach, the number of interventions or surgeries performed is equated with the experience of a surgeon or hospital. Finally, the volume is probably a surrogate parameter for individual factors like for example experience and structural aspects. The “selective referral” theory is based on the hypothesis that high-quality providers are able to attract more patients who are referred to this institution or find it by research [54]. Finally, the high-volume hospital effect is probably due to different factors such as organization, institution, nursing processes, expertise of care, and technology, and thus on a better structural and process quality which supports the requirement of minimum volume standards as basis for certification. On the other hand, experienced physicians may offer high quality also in smaller hospitals with lower case numbers and other factors such as empathy and experience cannot be assessed by means of certification. Studies on hospital volume and their feasibility in the German healthcare reality are regularly criticized because the data are mostly based on US American registry analyses of much earlier times, the healthcare settings of American trials cannot be easily compared with Germany, and current nationwide data for Germany were missing for a long time. Regarding some tumor entities such as colorectal and lung carcinomas, however, meanwhile also German trials could provide arguments for treatment in high-volume centers and show that the certification system led to an improved healthcare quality of oncological patients [56] [57] [58]. It may be expected that the certification of head and neck cancer centers also leads to improved outcomes of patients with head and neck cancer in Germany. Long-term follow-up data will have to confirm this hypothesis.

Up to now, there is no cut-off value between high- and low-volume centers for head and neck cancer defined by trials. For certification as head and neck cancer center, currently at least 75 primary cases are requested per year in consensus of the scientific societies. In 2017, an average of 146.4 primary cases per site (median: 135.5) were treated in certified head and neck cancer centers. The center with the highest volume treated 258 primary head and neck cancer cases [38]. The NCCN guidelines also mention the survival advantage in high-volume centers and recommend that patients with head and neck cancer should receive their treatment in centers with high oncological expertise [13].

4.1.2 Quality assurance of surgery

Beside the significance of the hospital volume, also the influence of the surgeon volume on the mortality of patients with head and neck cancer could be confirmed. Lin et al. [59] were the first who could show a correlation between surgical treatment volume and 5-year survival rate for oral cancer in a Taiwanese cohort. The correlation between surgeon volume and outcome after head and neck cancer surgery could be confirmed by further trials [47] [48] [60]. The relevance of the surgeon volume for the prognosis was included in the DKG-certification in that way that the names of the head and neck cancer surgeons have to be mentioned in the assessment and the head and neck cancer surgeons have to perform at least 30 oncological interventions (primary cases/recurrences) within 5 years and then, to maintain their qualification, at least 10 surgeries per year (primary cases/recurrences). This makes certainly sense because the experience of the single surgeon plays a crucial role regarding the quality of the treatment. This could also be revealed for neck dissection. In a collective of 375 surgeries, Morton et al. [61] demonstrated that the experience of a surgeon regarding the surgical therapy of head and neck carcinomas is associated with the number of resected lymph nodes and thus with the prognosis. In this collective, the most experienced surgeon removed on average 11 lymph nodes more than the group of unexperienced surgeons. In cases of surgeries performed by unexperienced surgeons there were significantly more recurrences. There was a learning curve showing that the lymph node removal increased by one lymph node every 17 neck dissections. Since the number of lymph nodes – as shown in numerous trials and meta-analyses – is associated with the survival, the lymph node yield is also a quality factor for good treatment [62] [63] [64]. Most trials were performed with a cut-off value of 18 lymph nodes [33] [65] [66] [67] [68] [69] [70].

Programs on surgical quality assurance for oncological patients lead to an improvement of the morbidity and mortality and to reduced costs [71] [72]. Worldwide there are different initiatives aiming at an extensive surgical quality assurance; the most important one probably is the National Surgical Quality Improvement Program (NSQIP) in which more than 200 North-American hospitals participate. Even if general and vascular surgery are the core areas of the program, the interest of other disciplines is growing and numerous specific modules are currently developed [73].

In order to improve the quality of head and neck cancer surgery, for example the MD Anderson Cancer Center has established an evaluation system to measure the physicians’ performance with the objective to find out whether the performance of a head and neck surgeon may be improved by feedback [74]. After an evaluation of a first cohort of head and neck interventions (2004–2008; 2618 patients), the surgeons received a risk-adjusted individual feedback. Afterwards the surgical interventions were assessed in a post-feedback cohort (2009–2019; 1389 patients). The parameters that were assessed encompassed the duration of the inpatient stay, perioperative use of blood products (24 hours), the necessity of revision surgery within 7 days after first surgery, the occurrence of postoperative infections, the necessity of readmission to the hospital, and the 30-days mortality rate. The procedures were classified into low acuity procedures (LAP: outpatient interventions or interventions with less than 2 postoperative inpatient days) and high acuity procedures (HAP: tumor resections requiring pedicled or free flap reconstruction [with an average inpatient stay of 11 days]). A comparison of the cohorts before and after feedback revealed a significant reduction of the inpatient duration (LAP: from 2.1–1.5 days [p=0.005]; HAP: from 10.5–7 days [p=0.003]). In cases of HAP, further a significant reduction of the postoperative surgical site infection rate and readmissions within 30 days after intervention were observed. The factors influencing the performance included the surgeon himself, the type of surgery (LAP vs. HAP), and the patients’ comorbidities. An investigation of the surgeon-specific improvement could show that 60% of the surgeons improved their performance for LAPs and half of the surgeons for HAPs. The incidence to have one or more negative performance indicators significantly reduced in the post-feedback group for LAPs from 39.1–28.6% (p<0.001) and likewise for HAPs from 60.9–53.5% (p=0.081). The initiators of the program come to the conclusion that regular performance and outcome evaluations are essential for continuous quality improvement and that a feedback system may be an effective tool.

In the context of surgical quality assurance, pathological aspects of quality assurance are highly relevant because they lead to the reliability of tumor staging, have therapeutic consequences for the patients, and allow predicting the prognosis. Due to the essential significance for the patients, the quality claim to histopathological diagnostics is extremely high. Instruments such as ring trials and second opinion procedures are therefore standard in pathology. A good cooperation and communication between surgeons and pathologists including the availability of precise clinical information is crucial to assure good quality.

4.2. Optimized therapy decisions based on interdisciplinary tumor boards

The most important structural element of interdisciplinary communication in head and neck cancer centers is the head and neck tumor board where therapy decisions are discussed. For different tumor entities, numerous studies have confirmed that therapy performed by a multidisciplinary team leads to better survival. A trial of the University of Philadelphia could show for head and neck carcinomas that the disease-specific survival of patients with head and neck cancer increased significantly from 52–75% (p=0.003) after introduction of a multidisciplinary tumor board. In addition, the post-tumor board cohort had a better overall survival and a lower mortality risk (HR: 0.48) [75]. In Germany, interdisciplinary tumor boards are required as standard of oncologic treatment in the national cancer plan as well as in the specific guidelines of the scientific societies. The background is that one discipline alone should not decide which therapy is optimal for the patient to be treated because of the complexity of oncologic diseases and their therapies. Otherwise the indispensable assessment of therapeutic options of other disciplines would be missing [76] [77]. In particular, the treatment recommendation for a patient is made independently from the initially treating discipline when submitting the case to an interdisciplinary tumor board. Tumor boards summarize the expertise of several disciplines so that the best possible treatment for the patients may be achieved and the treatment steps are coordinated which is a relevant aspect of quality assurance. Lamb et al. [78] could show in a systematic review that the jointly made decision of a tumor board differs from therapy planning of single physicians in up to 52% of the cases. In the context of oncologic certification, the regular organization of interdisciplinary tumor boards with the presence of an otolaryngologist, a maxillofacial surgeon, radiologist, pathologist, radiooncologist, and hematooncologist is obligatory. Based on the indication, further disciplines (such as nuclear medicine, plastic surgery etc.) must be invited. Hereby, the requirement of >95% of pretherapeutic tumor board presentations has to be fulfilled. The evaluations of head and neck cancer centers reveal that from 2013–2017 between 95.49% (in 2015) and 97.26% (in 2013) of the primary cases (median) were presented in tumor boards of the centers, finally 96.12% (in 2017), while 37 centers (68%) achieved the target of 95% of pretherapeutic presentations (first certification: 90%). Frequently mentioned reasons for the non-presentation before therapy are the tumor resection during the diagnostic intervention in one session, intraoperative incidental findings, urgent indication of surgery, and difficulties in coordination at interdisciplinary interfaces [38].

The fact that a tumor board is organized, however, is no guarantee for quality. Therefore, tumor boards should meet certain additional quality criteria. For this purpose, quality checklists were established such as the MDT-QuIC checklist [79]. Relatively simple measures may optimize the quality of tumor boards, for example a timely introduction of the cases so that all participants of the tumor board have the possibility to prepare the single cases. Further, the decision made by the tumor board should be documented transparently so that the jointly made decision is available for everyone. Finally, the quality of a tumor board always depends on the people and the available information. Clinical dashboards are a promising method to support future decision processes in such scenarios that are cognitively challenging [42].

Currently, the adherence to tumor board recommendations is not systematically controlled in the context of oncologic certification, although it is an important criterion of the process quality. In 2018, the University Hospital of Bonn presented a detailed analysis of its head and neck tumor board. The adherence to tumor board recommendations was analyzed in 812 patients who were discussed 1319 times between June 2014 and December 2016 in the tumor board. A total of 1081 recommendations (82%) were realized, among them 927 (70.3%) completely and 154 (11.7%) partly. In 8.7% of the cases, the implementation remained unclear. In 123 cases (9.3%) the actually received treatment deviated from the recommendation. The reasons for these deviations were the patients’ desire (45.5%), medical decision (26.8%), death of the patients (17.1%), and therapy in other places (2.4%). The deviation rate decreased from 15.2% in 2014 to 8.7% in 2015, and 7.8% in 2016 [80]. This fact indicates an improvement of the process quality. Up to now, it has not been systematically investigated if head and neck tumor boards lead to an increase of the patient numbers who are treated in the context of clinical trials even if this is an important expectation to interdisciplinary tumor boards [77]. This issue should be clarified by future analyses.

5. Patient-Orientation as Quality Criterion

5.1 Patient information and communication

Good oncologic treatment is also characterized by need-based patient information and communication. Conversational skills and communication are basic competences of clinically active physicians. Also the national cancer plan requests a strengthening of the communicative skills of all oncologic disciplines (goal of action 12) [7]. Insufficient communication has a negative effect on the quality of therapy and the treatment of patients. Cancer patients who do not feel well informed have significantly more depression and anxieties and a lower quality of life [81]. Finally, also the acceptance of therapeutic measures is influenced by how patients have been informed. In this context, also self-help groups might play a crucial role by providing the according information. One example is the consultation of patients before total laryngectomy by members of the Federal Association of Laryngectomized Patients (Bundesverband der Kehlkopfoperierten). Of course, there is no general recipe for the communication with cancer patients. Most recommendations are based on the concept of patient-orientation with development of specific communicative skills, e. g. the SPIKES model that suggests certain structures for conversations in which bad news have to be communicated [82] [83] [84]. However, mostly inter- and intrapersonal factors as well as situational conditions determine the communication between physician and patient.

Communication skills of the nursing staff are also highly important because the caring staff is most frequently in direct patient contact in hospitals. DKG-certified centers are obliged to employ oncologically trained professional nurses. In the context of further education, not only specific and demanding practical skills are learned, but also communicative, social, and pedagogic competences are extended. It could already be shown for patients suffering from breast cancer that specifically trained nursing staff could improve the patient satisfaction and therapy compliance [85].

An adequate patient information is supported by the guideline program on oncology that beside medical guidelines also provides patient guidelines with easily understandable information on the disease, diagnostics, therapy, and follow-up [21].

5.2 Right to obtain medical second opinion

In Germany, patients with oncologic diseases may obtain a medical second opinion paid by the health insurance. For patients, the second opinion may be an important way to get transparent, detailed, and balanced information and reduce uncertainties, but it may also create new ones, in particular when the first and second opinion vary significantly. So it is even more important to make a qualified first opinion in an interdisciplinary tumor board that may relieve the patient from the uncertainty of being at the mercy of a single opinion. For those who are asked for a second opinion, the efforts are sometimes very high even without additional examinations. Available imaging and findings have to be checked, the patient has to be examined, and the physician’s point of view regarding treatment and possible therapy options have to be discussed in order to make a reasonable and sound decision in the interdisciplinary tumor board.

5.3 Patient-oriented process design

Patient-centered process design becomes more and more important in head and neck oncology. The optimized logistics in hospitals allow reducing the waiting times for the patients, to economically apply cost-intensive resources, and to increase the patient satisfaction which is relevant for therapy and economics. Patient-centration is also promoted by oncologic certification. Waiting times for an appointment (requirement: less than 2 weeks) and also within the oncologic consultation (requirement: less than 60 minutes) have to be assessed and analyzed as factors of service quality of the hospitals. In addition, patient surveys are obligatory in order to identify the reasons for missing patient satisfaction.

5.4 Improvement of psychooncologic care

For patients and their relatives, oncologic diseases mean an enormous psychologic stress and may lead to a multitude of subsequent psychosocial problems in all areas of life. The national cancer plan requests that all cancer patients should receive an appropriate psychooncologic treatment in the inpatient as well as outpatient sector, if needed [7]. The S3-guideline on psychooncologic diagnostics, consultation, and treatment of adult cancer patients includes recommendations for the entire course of the cancer diseases as well as all sectors of medical care [86]. Interestingly, studies show that patients with head and neck carcinomas, beside patients with breast cancer and melanomas, have a prevalence for mental diseases above average [87], however, with regard to psychooncologic care they are underrepresented. Only a very low percentage of mentally stressed patients claims for psychooncologic support [88]. Since psychooncologic treatment of head and neck cancer patients is only rarely requested by the patients themselves, low-threshold and target group specific offers are highly relevant for these patients.

In the future, the psychooncologic care will play an even more important role with the background of increasing survival rates after tumor disease, and the existing structures will have to be enlarged. This is fostered by the DKG-certification, in this context the organization of respective screening procedures and the employment of psychooncologists is obligatory. As a side effect, relevant data that have not been assessed cross-regionally, such as for example the rate of psychooncologic treatment, will be centrally collected and evaluated. Already today trials confirm that patients who are treated in DKG-certified centers have a higher rate of psychooncologic treatment compared to those in non-certified institutions [89]. Over the past years in DKG-certified centers the percentage of psychoonocologic treatment in head and neck cancer patients increased from 19.2% (median in 2013) to 30.7% (median in 2017) [38]. This means that the centers have continuously improved their rate of psychooncologic co-treatment and thus better implemented the guideline recommendations. This led to a significant improvement of the inpatient care. However, a high-quality psychooncologic treatment has to be assured at the long term and nationwide, and also for outpatients. Until now, the offers for cancer patients and their relatives are not sufficient.

5.5 Patient-Reported Outcome (PRO)

Since many years, efforts are made to take into consideration the subjective perception of patients in the context of therapy decision in oncology and not to only rely on the physicians’ opinion and objective measurement values. One important assessment tool is the patient-reported outcome (PRO). The FDA (Food and Drug Administration) defines PROs as follows: “A PRO is a measurement of any aspect of a patient’s health status that comes directly from the patient (i. e., without the interpretation of the patient’s responses by a physician or anyone else)” [90]. PRO encompass all data that are gained through direct statements made by patients with regard to their health status and treatment, such as for example quality of life, symptoms, preferences, and patient satisfaction. In this way, the impairment of the patients in their mental, functional, emotional, and social well-being may be assessed. In cases of cancer patients, PROs provide important patient-specific information that are relevant for therapy control beside objective parameters such as therapy response, blood values, and side effects.

The assessment of PROs is typically made by means of a questionnaire or interview. Most frequently used in oncology and probably best validated PRO instruments are the questionnaire of QLQ-C30 of the EORTC and the questionnaire entitled “Functional Assessment of Cancer Therapy” (FACT-G) [91] [92] because they contain disease-specific modules for oncologic patients and are frequently applied in clinical routine. Today, digitization and modern data analysis allow continuous and structured collection and evaluation of PRO data. First computer-based programs for systematic assessment such as OncoFunction, OncoQuest, and OncoKompas are applied in hospitals [93] [94] [95] [96] [97]. First trials in this context show that beside the advantages, the implementation of PROs in clinical routine leads to organizational challenges [96]. A possibly smooth integration into existing processes and procedures is desirable. More recently developed software for smartphones allow that patients themselves document their health status, their symptoms, their physical function, and mental health and to report about them. This facilitates the direct implementation in treatment decisions.

PROs become more and more relevant also in clinical trials and thus they are also requested for approval authorities (e. g. FDA, European Medicines Agency [EMA]) regarding the clinical investigation for approval of oncologic pharmaceutics [90] [98]. However, PROs are also valuable in routine treatment and follow-up. For routine treatment, it could be proven that the assessment of PROs leads to an improved survival [99]. Out of 766 patients with metastatic solid tumors who had been treated at the Memorial Sloan Kettering Cancer Center in New York from 2007–2011 with chemotherapy, half of them were asked to fill out a questionnaire on the internet at least once per week containing questions about 12 frequently occurring side effects of cancer treatments while the other 50% of the patients participated in the usual treatment with regular controls in the hospital. Whenever the patients reported about the occurrence of a symptom or about deterioration in the internet questionnaire, an automated e-mail was sent to the treatment center so that the treating physicians could react immediately. Basch et al. [99] could show that the consideration of PRO did not only lead to a significant improvement of the health-related quality of life (34% vs. 18%) and to significantly reduced number of emergency admissions (34% vs. 41%) and hospitalization (45% vs. 49%), but also to a significantly longer overall survival from 26–31.2 months, while patients who submitted their PROs could be treated with chemotherapy according to the protocol for a longer time (8.2 vs. 6.3 months). In summary, a risk reduction for progression of 30% could be achieved; and a risk reduction of 20% in oncology is already considered as relevant additional benefit.

6. Increase of the Outcome Quality by Personalized Medicine

Quality is also reflected by the fact that therapy options are individually chosen based on the tumor stage but also the desire and the life situation of the patients. There should be enough time to be well and extensively informed. Hereby, the treating physicians have to assume the task to individually discuss all possible therapeutic options – even those that they cannot perform themselves – with every patient. The better understanding of molecular mechanisms of tumor pathogenesis and progression led to new approaches of targeted oncologic therapy. In the context of personalized cancer therapy, the analysis of tumor-specific molecular biological changes and targeted blockade of these changes should result in an improved therapeutic effect and response rate. The focus is mainly placed on growth factor receptors, various oncogenes, and processes of the immune escape of tumor cells. Even if head and neck carcinomas are considered as very heterogenic, in the last years some frequently occurring molecular alterations could be defined that allow targeted therapy. The concepts of genetically targeted tumor therapy are further promoted by the development of next generation sequencing which allows performing mutation analyses of genes with justifiable efforts [100]. Hereby, gene combinations (so-called panels), the entire exome, or the whole genome may be sequenced. In order to achieve quality standards, first guidelines for the performance and interpretation of tumor-genetic examinations have been developed [101] [102]. Currently, about 140 genes of head and neck carcinomas have been identified that in cases of mutations may promote tumor development by permanent activation (oncogenes) or deactivation (tumor suppressor genes). On average, one tumor contains two to eight of those mutations [13]. Large gene profile analyses of head and neck squamous cell carcinomas of the Cancer Genome Atlas Network could reveal genetic changes in the tumor suppressor genes of TP53 or CDKN2A but also in RB1, NOTCH1, and FAT1 [103].

In cases of a disease progress beyond the approved and guideline-based therapy options or patients with rare tumor diseases and missing guideline-based therapy options, molecular tumor boards (MTBs) provide the possibility to benefit from highly individualized therapy. In contrast to the established entity-specific interdisciplinary tumor boards, molecular tumor boards are larger interdisciplinary, multiprofessional, interinstitutional meetings where additionally also for example molecular biologists, human geneticists, bioinformaticians, and basic scientists are present in order to integrate the assessed molecular profile into an overall therapy concept depending on the molecular characteristics of the tumor. Beside weighting the identified mutation(s) it is important to know if a targeted medication exists, which evidence is available for the therapy in the diagnosed tumor entity or also independently from the entity, and how the therapy may be made available for the patient.

In the field of precision oncology, increasingly also entity limits are surpassed aiming at increasing the outcome quality for the patients (in particular the survival). Based on this principle, first cross-entity medication approvals were achieved depending on molecular alterations. For example, the checkpoint inhibitor Pembrolizumab was approved for patients whose tumor had microsatellite instability, regardless of the entity [104]. Larotrectinib, a tyrosine kinase inhibitor, was approved in the USA for treatment of metastatic solid tumors in which a NTRK fusion gene was found. NTRK fusion genes were found in more than 20 cancer entities up to now, among them for example also salivary gland tumors, but only in less than 1% of the patients [105]. The approval was made on the basis of data of a basket trial where 55 patients with different tumor entities such as breast cancer, carcinoma of the bile duct, colorectal cancer, gastrointestinal stroma tumors, fibrosarcomas, lung cancer, MASC tumors of the salivary glands, melanomas, pancreatic carcinomas, thyroid carcinomas, and different sarcomas were included. The overall response rate amounted to 75% after central evaluation (among them 13% complete responses and 62% partial responses) and 80% after principal investigator assessment. An average of 1.8 months passed until treatment response was observed. After one year, 71% of the patients were still in remission and 55% of all patients remained progress-free. The treatment was well tolerated, none of the patients had to interrupt the therapy due to drug-related side-effects [104].

With the background of missing evidence, targeted therapies recommended in molecular tumor boards should be done in clinical trials (e. g. basket trials), alternatively, patients might receive the treatment as individual off-label therapy [106]. In particular for off-label approaches, a structured and standardized documentation of the further course of the disease (e. g. in registries) with assessment of the therapy response is highly relevant because scientifically sound evidence for precision-oncologic approaches is not yet available. Up to now, it could be shown that at least subgroups of patients may benefit from personalized cancer treatment based on molecular tumor markers [107]. In a retrospective analysis of 165 cancer patients who were discussed in the tumor board of the Mayo Clinic from 2012–2015 [108], mutations that could be therapeutically targeted were identified in 65% (92/141) of the patients, 32% (29/92) received targeted therapy with approved medication or within clinical trials. Only one of these patients suffered from head and neck cancer. In 141 of 165 patients, a genomic analysis was performed. The most frequent reasons not to conduct this analysis, were the patients’ refusal and economic reasons. The treatment response amounted to 45% (13/29). A standard-of-care (SOC) therapy was performed in 15% (14/92) of the tested patients before exhaustion of the SOC options, 71% (10/14) of these patients responded well to the treatment. More than 35% (34/92) of the patients with therapeutically targetable mutations were not treated; the most frequently mentioned reasons were death and refusal by the patients [108]. This shows that the implementation of targeted therapies in individual cases is not trivial. Several prospective trials where genomic sequencing of the tumor was performed confirm that in about 30–60% of the cases therapeutically targetable or potentially addressable molecular alterations are found [109] [110] [111].

Up to now, a significant improvement of the outcome quality due to personalized therapy could not be sufficiently proven. The prospective randomized SHIVA trial conducted in 8 French centers investigated the effectiveness of several molecular agents that are approved in France. These agents were applied, apart from their indication, in patients with metastatic solid tumors after standard therapy based on the molecular tumor profiles. The molecular tumor profile of each patient was assessed after tumor biopsy by means of genomic examination. 40% of the patients could be classified due to their molecular profile into one of 10 previously defined treatment arms with different target substances. The suggested targeted therapy was applied in 99 patients after randomization, while 96 patients continued the therapy chosen by their treating physicians without knowing their molecular findings. Surprisingly, there was no significant difference between both groups with regard to progression-free and overall survival; and the targeted therapy was associated with higher toxicities [112]. However, it must be pointed out that many of the treated mutations were no driver mutations. Other prospective trials such as for example the NCIMATCH trial that assigns patients to one of about 40 treatment arms based on a panel testing of 143 genes showed first positive results. Until now, more than 6000 patients were included, 10% of them could be treated based on an targetable alteration in one of the therapy arms [113].

In contrast to the SHIVA trial, meta-analyses that compared personalized therapy with non-personalized treatment could show that personalized targeted therapies lead to higher response rates and longer overall survival than unspecific cytostatic substances [114]. While about 0.7% of the oncologic patients could benefit from targeted molecular therapy in 2006, their number increased to 4.9% in 2018 [115].

In the future, the quality improvement of personalized therapy will also depend on the standardization of the recommendation process in molecular tumor boards. Rieke et al. [116] could show with four fictive patient cases that were evaluated in five different molecular tumor boards of four different countries that the estimation of the relevance of molecular alterations and the derived therapy recommendations varied sometimes enormously between the academic centers. For one patient, the treatment recommendations of three molecular tumor boards were identical, for the other three patients only two of five tumor boards came to the same treatment conclusions. In summary, a heterogenic interpretation of tumor and germ line aberrations as well as different prioritizations of the therapeutic value were revealed. In the future, comparing analyses of board recommendations are essential in order to improve rational decision making and to achieve standardization. First websites on personalized oncologic medicine such as www.personalizedcancertherapy.org have been established to provide an online resource that might support the identification of possible therapy options for patients with oncogenic genomic alterations [117]. Recently, the ESMO presented the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) that distinguishes 6 groups of genetic aberrations based on the available evidence and the implications for the practice [118].

Precision oncology has high structural and content-related requirements which makes the implementation of molecular tumor boards rather difficult. The mostly long period between the start of tissue examination and therapy recommendation in patients with advanced oncologic diseases represents a clear limitation. Therapy planning is often performed based on the biological rationale because clinical trials and high-grade evidence are missing. So it often remains unclear if the detected mutation is actually the driver mutation. Finally, for many genetic alterations no targeted therapy is available. The current evidence does not suffice to justify the off-label use of targeted substances in routine care based on the molecular identification of treatable mutations. As individual therapy or within clinical trials, treatment is of course possible. Overall, therapeutic approaches of stratifying medicine still have to prove their benefit for patients with head and neck cancer. In the near future, the quality of data management will certainly play a crucial role. Hereby, medically integrated information systems may possibly help [42]. On the other hand it will be relevant to check the validity of biomarkers in clinical trials. This is also important with the background of financing the precision-oncologic approach because the enormous efforts, especially of molecular diagnostics, molecular tumor boards, and therapy, are associated with extremely high costs.

7. Quality in Trials on Head and Neck Oncology

Even if randomized controlled trials provide decisive information about the optimal therapy of head and neck carcinomas, the majority of the patients is treated outside of clinical trials. In particular randomized controlled trials on the surgical therapy of head and neck cancer are missing. One reason for this fact is that surgical trials are associated with various difficulties. Their conduction is complex and the reproducibility is difficult because a real standard of the surgical performance is difficult to achieve. The experience and the technical skills of the surgeons play a relevant role. Quality assurance in surgical oncology is more difficult compared to internal oncology or radiotherapy where the doses are standardized and the toxicities are well classified. A total of about 20% of all surgical clinical trials are interrupted and less than half of them are finally published. Furthermore, only 5% of the oncologic grants go to surgical trials which makes development in this area rather difficult due to the limited financing [119].

For a long time, there were nearly no clinical trials in surgical head and neck oncology. In the last years, the introduction of robotic surgery led to an increased trial activity in this field. The dynamic development of immunotherapy of head and neck tumors with checkpoint inhibitors that improved the prognoses after first and second line therapies of metastatic and recurrent head and neck cancer [120] [121] [122] also led to a clear increase of clinical trials in head and neck cancer therapy in different settings (palliative, neoadjuvant, adjuvant).

The reporting criteria for clinical trials were continuously adapted to the CONSORT (Consolidated Standards of Reporting Trials) criteria within the last years [123] [124]. Despite these efforts, however, randomized surgical trials often remain of poor quality. Carlton et al. could show in a quality analysis of 38 randomized controlled trials on oncologic head and neck surgery that in trials where head and neck surgeons were either the first author, the last author, or the first and last author of the publications a tendency towards lower quality of the trials could be observed – compared to trials where the first and/or last author were no surgeons [125]. Non-surgeons rather reported about critical elements with regard to the hypothesis, sample size, randomization, and appropriateness of centers. Overall, the authors came to the conclusion that the quality of randomized controlled trials about head and neck oncology was rather poor. So they recommend that the education and training of head and neck surgeons should include the conception, conduction, and interpretation of clinical trials.

The European Organization for Research and Treatment of Cancer (EORTC) was one of the leading organizations that already early started developing quality initiatives for oncology in Europe and it increasingly cares for measures of quality assurance. In 1989, the first committee for quality assurance was founded in order to supervise the conduction of clinical trials [126]. First measures of quality assurance were introduced in the field of internal oncology with the implementation of guidelines and protocols for the application of chemotherapeutics. In 2011, the radiotherapy group of the EORTC defined measures of quality assurance in order to reduce the variability and uncertainties in the context of the different steps of treatment planning and the actual patient irradiation including – but not limited to – the positioning of the patients and the precise dose application of the target volume [127]. This quality assurance program aims at defining the range of acceptable deviations, at recognizing possible reasons for larger deviations, and at developing mechanisms to correct and avoid these deviations [128]. The first surgical quality assurance program of the EORTC with regard to head and neck carcinomas was developed for the EORTC 24954 trial that was initiated in 1990 [129]. Since then, the EORTC continues its activities and efforts to improve the quality of surgery in clinical trials. One example is the platform named SURCARE, which is a joint project with the European Society of Surgical Oncology and the Japanese Clinical Oncology Group that shall facilitate the standardization of surgery techniques and the central monitoring of surgical results [130]. Currently, SURCARE is applied in the context of the best-of trial (EORTC 1420) to perform quality assurance for the surgery arm in completion of quality assurance of radiotherapy in the radiotherapy arm. In 2018, the EORTC Head and Neck Group presented a catalogue of quality requirements for head and neck surgery that shall present a precondition for participation in future trials on head and neck surgery [131]. The aim is a minimum quality level of the centers participating in the studies according to the existing European guidelines for the accreditation of a head and neck cancer center and adapted to EORTC standards. The catalogue of quality requirements refers to the structures of the clinical center as well as regulations of process adherence while study-specific and non-study-specific criteria are differentiated ([Tables 4] and [5]).

Investigations confirm the effect of expertise of hospitals that treat many patients in clinical trials on the overall survival. Wuthrick et al. [132] analyzed the survival of 471 patients with head and neck carcinomas staged III/IV depending on the treating center in the RTOG-0129 trial. Based on the recruiting in 21 RTOG trials from 1997–2002, the participating centers were classified into centers with low recruitment (historically low-accruing centers [HLACs]) and high recruitment (historically high-accruing centers [HHACs]). HLACs recruited a median of 4 patients between 1997 and 2002 in RTOG trials, whereas HHACs recruited a median of 65 patients. Despite better performance state of the patients at HLACs and tumors with lower T stage, patients in HLACs had a significantly poorer 5-year overall survival (51%) than patients in HHACs (69%). The multivariate analysis revealed that the factor of HHAC with a hazard ratio of 1.01 (p<0.001) was similar to the prognostic factors of T stage (HR: 2.08) and HPV stage (HR: 2.34). Treatment in HLACs was associated with a higher mortality risk of 91% after adjustment by the prognostic factors, after adjustment by deviations of the radiotherapy protocols the increased mortality risk still amounted to 72% [132]. The DELOS-II trial could show that the overall survival and the survival with larynx preservation were significantly better in centers that recruited more than 13 patients into the trial compared to centers that recruited less patients [133]. This emphasized the value of study groups that within their work for the trials may also approach quality aspects in the sense of healthcare research and supports the requirements of the DKG that the percentage of patients treated in clinical trials should amount at least to 5% in certified centers. This requirement was achieved by 47 sites (87%) in 2017. Among the primary cases, 15% of the patients (median) were treated in clinical trials [38]. At the long term, the requirement regarding a trial rate will lead to an improved infrastructure for trials and also to an increased inclusion of non-academic hospitals in the trial landscape. The German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie, DGHNOKHC) supports the establishment of a high-quality infrastructure for clinical trials by means of the German Study Center for Oto-Rhino-Laryngology, Head and Neck Surgery (Deutsches Studienzentrum für HNO-Heilkunde, Kopf- und Hals-Chirurgie, DSZ-HNO) that helps with planning and conducting selected clinical trials up to publication. Also the interdisciplinary study group of head and neck tumors (Interdisziplinäre Arbeitsgruppe Kopf-Hals-Tumoren, IAG-KHT) of the DKG supports the generation of clinical trials and the realization of German multicenter trials.

8. Quality of Follow-up in Head and Neck Oncology

One important part of the entire therapy is a structured follow-up of cancer patients that should be performed in close communication with the practicing specialists. Beside the first diagnosis that is usually made by a practicing physician, the colleagues in private practices play the decisive role in the care of cancer patients. According to national and international guidelines, structured after-care is reasonable [19] [20] [134], most notably to early detect possible recurrences or second primary cancers. Furthermore, the post-therapeutic functional status, in particular speaking and swallowing, must be assessed and the necessity of rehabilitative or supportive measures such as speech therapy, pain management, nutrition management, physiotherapy, and lymph drainage has to be estimated [135]. Even in cases of symptom-free patients, three months are considered as suitable for follow-up appointments for the first and second year and 6 months for year 3 to 5. After the 5^th year, it can be decided individually if further follow-up seems to be necessary [19] [20]. The main focus of follow-up is placed on the clinical examination including endoscopy. There is no defined time for performing imaging during follow-up except that patients with primary radio(chemo)therapy are recommended to undergo CT scan to exclude residual tumors or residual metastases about 8–12 weeks after finalization of the therapy [20]. The structured assessment of the quality of life in the context of follow-up may early indicate complications or recurrences. Hereby, the patient reported outcome gains in importance. First programs on systematic assessment of the PRO such as OncoFunction, OncoQuest, and OncoKompas are applied in hospitals. For other entities the evidence of improved prognosis by assessing the PROs was already given (see Chapter 5.5) [99].

Beside functional deficits, cancer diseases lead to socio-economic consequences for the patients and the society. Cancer patients for example have a significantly higher risk to lose their employment [136]. Therefore, high-quality follow-up also includes the reintegration of patients in social life and the resumption of work. Patients with head and neck tumors have a clearly higher risk for long-term unemployment compared to patients with other tumor entities [137]. An analysis of 750 German tumor patients revealed that 32.8% of the head neck cancer patients wish early retirement, while it were only 22% in the entire cohort [138]. This study is confirmed by the fact that in 2013 tumors of the oral cavity and the pharynx (11.9%) in men led to the third most retirements following lung (19.9%) and colon cancer (12.3%) due to the reduction of the earning capacity because of oncologic diseases in Germany [2]. However, nearly 50% of the cancer patients in Germany would like to have more information about the possibilities of professional reintegration and support for resuming their jobs [139]. In the future, this aspect will become more and more relevant also because of the fact that head and neck cancer patients live longer after their cancer disease. Programs that promote the reintegration in professional life will be required [140].

Some clinical registries, so-called after-care coordination centers, also organize cancer follow-up by informing physicians about new recommendations of after-care and by being available as data sources. In this way, the coordination centers may help to analyze and improve the quality of oncologic therapy. In summary, a well-documented high-quality follow-up and the participation in quality assuring measures for assessing long-term data is a precondition for high-quality patient treatment and the future improvement of scientific evidence.

9. Conclusion and Outlook

Currently, in Germany the quality standards in head and neck oncology are probably the best developed in otolaryngology. The basis were the national cancer plan and the KFRG that paved the way for quality improvement in oncology in Germany. In 56 head and neck cancer centers, a guideline-based, multidisciplinary treatment of head and neck cancer is assured. By evaluating the parameters of head and neck cancer centers, not only the quality of routine treatment may be assessed but it could be proven that the certification of oncologic institutions may contribute to an improved healthcare quality. The evidence of improved survival by treatment in certified centers, however, is not yet available for head and neck cancer. The stronger focus that is placed on the patients’ perspective leads to the fact that new quality criteria (PRO) are applied in head and neck oncology. The study activity in head and neck oncology is currently increasing – in Germany it is fostered by certification requirements – and European quality requirements to participate in clinical trials have been presented. Approaches regarding precision oncology are more and more available; in this context it will be essential to create structures that enable many patients to benefit from these innovative therapy concepts. The implementation of quality reporting by clinical cancer registries will provide further impulses for an optimal oncologic care in Germany, as far as the objective of national overall assessment is achieved. The aim should be to allow patients with head and neck cancer the best possible diagnostic, therapeutic, and posttherapeutic care and to cure them from their cancer disease based on interdisciplinary cooperation of the treating staff in certified head and neck cancer centers, adhering to nationally and internationally acknowledged guidelines as well as internal and external quality assurance measures.

Interessenkonflikt

Die Autoren geben an, dass kein Interessenkonflikt besteht.

• Literatur

• 1 Lohr KN, Schroeder SA. A Strategy for Quality Assurance in Medicare. N Engl J Med 1990; 322: 707-712
  PubMedSearch in Google Scholar
• 2 Bericht zum Krebsgeschehen in Deutschland 2016. Kapitel 4. Folgen von Krebserkrankungen. Robert-Koch-Institut. 2016
  PubMed
• 3 https://www.krebsdaten.de/Krebs/DE/Content/Krebsarten/Mundhoehle_Rachenkrebs/mundhoehle_rachen_node.html;jsessionid=8559195E959168467BBECD37C5E30FB2.1_cid298
  PubMed
• 4 https://www.krebsdaten.de/Krebs/DE/Content/Krebsarten/Kehlkopfkrebs/kehlkopfkrebs_node.html
  PubMed
• 5 Donabedian A. Evaluating the quality of medical care. 1966. Milbank Q 2005; 83: 691-729
  CrossrefPubMedSearch in Google Scholar
• 6 (Muster-)Berufsordnung für die in Deutschland tätigen Ärztinnen und Ärzte - MBO-Ä 1997 – in der Fassung der Beschlüsse des 114. Deutschen Ärztetages 2011 in Kiel https://www.bundesaerztekammer.de/fileadmin/user_upload/downloads/MBO_08_20112.pdf
  PubMed
• 7 Nationaler Krebsplan https://www.bundesgesundheitsministerium.de/fileadmin/ Dateien/5_Publikationen/Praevention/Broschueren/Broschuere_Nationaler_Krebsplan.pdf
  PubMed
• 8 Hamburgisches Krebsregister. Hamburger Krebsdokumentation 1995–1998. Hamburgisches Krebsregister, Hamburg 2001
  PubMed
• 9 Katalinic A, Hense HW, Becker N. Krebsregistrierung in Deutschland. Onkologe 2006; 12: 1084-1093
  CrossrefPubMedSearch in Google Scholar
• 10 Ministerium für Frauen, Arbeit, Gesundheit und Soziales.Morbidität und Mortalität an bösartigen Neubildungen im Saarland 1996 und 1997, Jahresbericht des Saarländischen Krebsregisters. Epidemiologisches Krebsregister Saarland, Saarbrücken. 2000
  PubMedSearch in Google Scholar
• 11 De Angelis R, Sant M, Coleman MP, Francisci S, Baili P, Pierannunzio D, Trama A, Visser O, Brenner H, Ardanaz E, Bielska-Lasota M, Engholm G, Nennecke A, Siesling S, Berrino F, Capocaccia R. EUROCARE-5 Working Group. Cancer survival in Europe 1999–2007 by country and age: results of EUROCARE-5- a population-based study. Lancet Oncol 2014; 15: 23-34
  CrossrefPubMedSearch in Google Scholar
• 12 Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS. Evidence based medicine: what it is and what it isn‘t. BMJ 1996; 312: 71-72
  CrossrefPubMedSearch in Google Scholar
• 13 NCCN Guidelines. Head and neck cancer https://www.nccn.org/store/login/login.aspx?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf
  PubMed
• 14 Koyfman SA, Ismaila N, Holsinger FC. Management of the Neck in Squamous Cell Carcinoma of the Oral Cavity and Oropharynx: ASCO Clinical Practice Guideline Summary. J Oncol Pract 2019; 15: 273-278
  CrossrefPubMedSearch in Google Scholar
• 15 Quon H, Vapiwala N, Forastiere A, Kennedy EB, Adelstein DJ, Boykin H, Califano JA, Holsinger FC, Nussenbaum B, Rosenthal DI, Siu LL, Waldron JN. Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma: American Society of Clinical Oncology Endorsement of the American Society for Radiation Oncology Evidence-Based Clinical Practice Guideline. J Clin Oncol 2017; 35: 4078-4090
  CrossrefPubMedSearch in Google Scholar
• 16 Forastiere AA, Ismaila N, Lewin JS, Nathan CA, Adelstein DJ, Eisbruch A, Fass G, Fisher SG, Laurie SA, Le QT, O'Malley B, Mendenhall WM, Patel S, Pfister DG, Provenzano AF, Weber R, Weinstein GS, Wolf GT. Use of Larynx-Preservation Strategies in the Treatment of Laryngeal Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 2018; 36: 1143-1169
  CrossrefPubMedSearch in Google Scholar
• 17 Grégoire V, Lefebvre JL, Licitra L, Felip E. EHNS-ESMO-ESTRO Guidelines Working Group . Squamous cell carcinoma of the head and neck: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21 Suppl 5 v184-v186
  CrossrefPubMedSearch in Google Scholar
• 18 Chan AT, Grégoire V, Lefebvre JL, Licitra L, Hui EP, Leung SF, Felip E. EHNS–ESMO–ESTRO Guidelines Working Group. Nasopharyngeal cancer: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012; 23 Suppl 7 vii83-vii85
  CrossrefPubMedSearch in Google Scholar
• 19 S3-Leitlinie Diagnostik und Therapie des Mundhöhlenkarzinoms. AWMF-Register-Nummer (007-100OL) Version 2.0 12.2012 https://www.awmf.org/uploads/tx_szleitlinien/007-100OLl_S3_Mundhöhlenkarzinom_122012-122015-abgelaufen.pdf
  PubMed
• 20 S3-Leitlinie Diagnostik, Therapie und Nachsorge des Larynxkarzinoms. Langversion 1.0– Januar 2019, AWMF-Registernummer: 017/076OL https://www.awmf.org/uploads/tx_szleitlinien/017-076OLl_S3_Larynxkarzinom_2019-02.pdf
  PubMed
• 21 Leitlinienprogramm Onkologie https://www.leitlinienprogramm-onkologie.de
  PubMed
• 22 Renninger C. Living guidelines: Anspruch und Wirklichkeit in der Onkologie. https://www.coliquio.de/wissen/onkologie-kompakt-100/Living-Guidelines-100
  PubMed
• 23 Akl EA, Meerpohl JJ, Elliott J, Kahale LA, Schünemann HJ. Living Systematic Review Network. Living systematic reviews: 4. Living guideline recommendations. J Clin Epidemiol 2017; 91: 47-53
  CrossrefPubMedSearch in Google Scholar
• 24 Grimshaw JM, Thomas RE, MacLennan G, Ramsay CR, Vale L, Whitty P, Eccles MP, Matowe L, Shirran L, Wensing M, Dijkstra R, Donaldson C. Effectiveness and efficiency of guideline dissemination and implementation strategies. Health technology assessment 2004; 8: 1-72
  PubMedSearch in Google Scholar
• 25 Swegal WC, Herbert RJ, Eisele DW, Chang J, Bristow RE, Gourin CG. Observed-to-expected ratio for adherence to treatment guidelines as a quality of care indicator for laryngeal cancer. Laryngoscope. 2019; Jun 6 [Epub ahead of print]
  CrossrefPubMedSearch in Google Scholar
• 26 Lewis CM, Nurgalieva Z, Sturgis EM, Lai SY, Weber RS. Improving patient outcomes through multidisciplinary treatment planning conference. Head Neck 2016; 38 Suppl 1 E1820-E1825
  CrossrefPubMedSearch in Google Scholar
• 27 Gourin CG, Herbert RJ, Quon H, Fakhry C, Kiess AP, Eisele DW, Frick KD. Quality of care and short and long-term outcomes of oropharyngeal cancer care in the elderly. Head Neck. 2019; Jul 11 [Epub ahead of print]
  CrossrefPubMedSearch in Google Scholar
• 28 Alle onkologischen S3-Leitlinien – jetzt auch als App! Forum 2019; 34: 130
  PubMed
• 29 McGlynn EA, Asch SM. Developing a clinical performance measure. Am J Prev Med 1998; 14 (3 Suppl) 14-21
  CrossrefPubMedSearch in Google Scholar
• 30 Sens B, Fischer B, Bastek A, Eckardt J, Kaczmarek D, Paschen U, Pietsch B, Rath S, Ruprecht T, Thomeczek C, Veit C, Wenzlaff P. Begriffe und Konzepte des Qualitätsmanagements – 3. Auflage. . GMS Med Inform Biom Epidemiol 2007; 3: Doc05 http://www.egms.de/en/journals/mibe/2007- 3/mibe000053.shtml
  PubMedSearch in Google Scholar
• 31 Standard Operating Procedures (SOPs) http://www.ccc-netzwerk.de/arbeits-gruppen/standard-operating-procedures.html
  PubMed
• 32 Heimpl H. Zur Bedeutung nationaler und lokaler Leitlinien für ärztliche Entscheidungen. Medizinische Klinik 2003; 98: 226-230
  CrossrefPubMedSearch in Google Scholar
• 33 Cramer JD, Speedy SE, Ferris RL, Rademaker AW, Patel UA, Samant S. National evaluation of multidisciplinary quality metrics for head and neck cancer. Cancer 2017; 123: 4372-4381
  CrossrefPubMedSearch in Google Scholar
• 34 Mensah J, Graeven U, Wesselmann S. Nationales Zertifizierungsprogramm Krebs. Der Onkologe 2017; 23: 711-718
  CrossrefPubMedSearch in Google Scholar
• 35 Klauber J, Geraedts M, Friedrich J, Wasem J. Hrsg Krankenhaus-Report 2019. Das digitale Krankenhaus. Springer; Berlin Heidelberg:
• 36 Deutsche Krebsgesellschaft startet Pilotprojekt zur ärztlichen Zweitmeinung. Forum. 2019 34. 230
  PubMedSearch in Google Scholar
• 37 Adam H, Sibert NT, Bruns J, Wesselmann S. Krebspatienten qualitätsgesichert, multidisziplinär und evidenzbasiert versorgen: das Zertifizierungssystem der Deutschen Krebsgesellschaft. BARMER Gesundheitswesen aktuell 2018; 136-155
  PubMedSearch in Google Scholar
• 38 Kennzahlenauswertung 2019. Jahresbericht der zertifizierten Kopf-Hals-Tumorzentren https://www.onkozert.de/wordpress/wp-content/uploads/2019/05/khtz_jahresbericht-2019-A1_190521.pdf?v=15484791
  PubMed
• 39 Prognos 2018: Endbericht „Nutzen, Mehraufwand und Finanzierung von Onkologischen Spitzenzentren, Onkologischen Zentren und Organkrebszentren“. Im Auftrag der Deutschen Krebshilfe und der Deutschen Krebsgesellschaft https://www.krebshilfe.de/fileadmin/Downloads/PDFs/Stellungnahmen/Prognos_Endbericht_Deutsche_Krebshilfe.pdf
  PubMed
• 40 https://www.onkozert.de/organ/kopf-hals/
  PubMed
• 41 Kowalski C, Graeven U, von Kalle C, Lang H, Beckmann MW, Blohmer JU, Burchardt M, Ehrenfeld M, Fichtner J, Grabbe S, Hoffmann H, Iro H, Post S, Scharl A, Schlegel U, Seufferlein T, Stummer W, Ukena D, Ferencz J, Wesselmann S. Shifting cancer care towards multidisciplinarity: the cancer center certification program of the German cancer society. BMC Cancer 2017; 17: 850
  CrossrefPubMedSearch in Google Scholar
• 42 Oeser A, Gaebel J, Dietz A, Wiegand S, Oeltze-Jafra S. Information architecture for a patient-specific dashboard in head and neck tumor boards. Int J Comput Assist Radiol Surg 2018; 13: 1283-1290
  CrossrefPubMedSearch in Google Scholar
• 43 Wiegand S, Dietz A. Vor- und Nachteile eines Zertifizierungsverfahrens aus Sicht eines Kopf-Hals-Tumorzentrums. Der Onkologe 2017; 23: 719-726
  CrossrefPubMedSearch in Google Scholar
• 44 Luft HS, Bunker JP, Enthoven AC. Should operations be regionalized? The empirical relation between surgical volume and mortality. NEJM 1979; 301: 1364-1369
  CrossrefPubMedSearch in Google Scholar
• 45 Begg CB, Cramer LD, Hoskins WJ, Brennan MF. Impact of hospital volume on operative mortality for major cancer surgery. JAMA 1998; 280: 1747-1751
  CrossrefPubMedSearch in Google Scholar
• 46 Birkmeyer JD, Siewers AE, Finlayson EV, Stukel TA, Lucas FL, Batista I, Welch HG, Wennberg DE. Hospital volume and surgical mortality in the United States. NEJM 2002; 346: 1128-1137
  CrossrefPubMedSearch in Google Scholar
• 47 Eskander A, Merdad M, Irish JC, Hall SF, Groome PA, Freeman JL, Urbach DR, Goldstein DP. Volume-outcome associations in head and neck cancer treatment: a systematic review and meta-analysis. Head Neck 2014; 36: 1820-1834
  CrossrefPubMedSearch in Google Scholar
• 48 Eskander A, Irish J, Groome PA, Freeman J, Gullane P, Gilbert R, Hall SF, Urbach DR, Goldstein DP. Volume-outcome relationships for head and neck cancer surgery in a universal health care system. Laryngoscope 2014; 124: 2081-2088
  CrossrefPubMedSearch in Google Scholar
• 49 Redmann AJ, Yuen SN, Von Allmen D, Rothstein A, Tang A, Breen J, Collar R. Does Surgical Volume and Complexity Affect Cost and Mortality in Otolaryngology-Head and Neck Surgery?. Otolaryngol Head Neck Surg 2019; 16: 194599819861524
  PubMedSearch in Google Scholar
• 50 Cheung MC, Koniaris LG, Perez EA, Molina MA, Goodwin WJ, Salloum RM. Impact of hospital volume on surgical outcome for head and neck cancer. Ann Surg Oncol 2009; 16: 1001-1009
  CrossrefPubMedSearch in Google Scholar
• 51 Lassig AA, Joseph AM, Lindgren BR, Fernandes P, Cooper S, Schotzko C, Khariwala S, Reynolds M, Yueh B. The effect of treating institution on outcomes in head and neck cancer. Otolaryngol Head Neck Surg 2012; 147: 1083-1092
  CrossrefPubMedSearch in Google Scholar
• 52 Chen AY, Fedewa S, Pavluck A, Ward EM. Improved survival is associated with treatment at high-volume teaching facilities for patients with advanced stage laryngeal cancer. Cancer 2010; 116: 4744-4752
  CrossrefPubMedSearch in Google Scholar
• 53 Grover S, Swisher-McClure S, Mitra N, Li J, Cohen RB, Ahn PH, Lukens JN, Chalian AA, Weinstein GS, O'Malley Jr BW, Lin A. Total laryngectomy versus larynx preservation for T4a larynx cancer: Patterns of care and survival outcomes. Int J Radiat Oncol Biol Phys 2015; 92: 594-601
  CrossrefPubMedSearch in Google Scholar
• 54 Luft HS, Hunt SS, Maerki SC. The volume-outcome relationship: practice-makes-perfect or selective-referral patterns?. Health Serv Res 1987; 22: 157-182
  PubMedSearch in Google Scholar
• 55 Markar SR, Karthikesalingam A, Thrumurthy S, Low DE. Volume-outcome relationship in surgery for esophageal malignancy: systematic review and meta-analysis 2000-2011. J Gastrointest Surg 2012; 16: 1055-1063
  CrossrefPubMedSearch in Google Scholar
• 56 Hoffmann H, Passlick B, Ukena D, Wesselmann S. Chirurgische Therapie des Lungenkarzinoms: Argumente für die Behandlung in großen Zentren. Zentralbl Chir 2019; 144: 62-70
  Thieme ConnectPubMedSearch in Google Scholar
• 57 Trautmann F, Reissfelder C, Pecqueux M, Weitz J, Schmitt J. Evidence-based quality standards improve prognosis in colon cancer care. Eur J Surg Oncol 2018; 44: 1324-1330
  CrossrefPubMedSearch in Google Scholar
• 58 Völkel V, Draeger T, Gerken M, Fürst A, Klinkhammer-Schalke M. Langzeitüberleben von Patienten mit Kolon und Rektumkarzinomen: Ein Vergleich von Darmkrebszentren und nicht zertifizierten Krankenhäusern. Gesundheitswesen 2018; Apr 19 [Epub ahead of print]
  Thieme ConnectPubMedSearch in Google Scholar
• 59 Lin CC, Lin HC. Effects of surgeon and hospital volume on 5-year survival rates following oral cancer resections: the experience of an Asian country. Surgery 2008; 143: 343-351
  CrossrefPubMedSearch in Google Scholar
• 60 Broome M, Juilland N, Litzistorf Y, Monnier Y, Sandu K, Pasche P, Plinkert PK, Federspil PA, Simon C. Factors Influencing the Incidence of Severe Complications in Head and Neck Free Flap Reconstructions. Plast Reconstr Surg Glob Open 2016; 4: e1013
  CrossrefPubMedSearch in Google Scholar
• 61 Morton RP, Gray L, Tandon DA, Izzard M, McIvor NP. Efficacy of neck dissection: are surgical volumes important?. Laryngoscope 2009; 119: 1147-1152
  CrossrefPubMedSearch in Google Scholar
• 62 Cheraghlou S, Otremba M, Kuo Yu P, Agogo GO, Hersey D, Judson BL. Prognostic Value of Lymph Node Yield and Density in Head and Neck Malignancies. Otolaryngol Head Neck Surg 2018; 158: 1016-1023
  CrossrefPubMedSearch in Google Scholar
• 63 de Kort WWB, Maas SLN. Van Es RJJ, Willems SM. Prognostic value of the nodal yield in head and neck squamous cell carcinoma: A systematic review. Head Neck 2019; 41: 2801-2810
  CrossrefPubMedSearch in Google Scholar
• 64 Merz S, Timmesfeld N, Stuck BA, Wiegand S. Impact of Lymph Node Yield on Outcome of Patients with Head and Neck Cancer and pN0 Neck. Anticancer Res 2018; 38: 5347-5350
  PubMedSearch in Google Scholar
• 65 Son H-J, Roh J-L, Cho K-J, Choi S-H, Nam SY, Kim SY. Nodal factors predictive of recurrence and survival in patients with oral cavity squamous cell carcinoma. Clin Otolaryngol 2017; 43: 470-476
  PubMedSearch in Google Scholar
• 66 Divi V, Chen MM, Nussenbaum B, Rhoads KF, Sirjani DB, Holsinger FC, Shah JL, Hara W. Lymph node count from neck dissection predicts mortality in head and neck cancer. J Clin Oncol 2016; 34: 3892-3897
  CrossrefPubMedSearch in Google Scholar
• 67 Divi V, Harris J, Harari PM, Cooper JS, McHugh J, Bell D, Sturgis EM, Cmelak AJ, Suntharalingam M, Raben D, Kim H, Spencer SA, Laramore GE, Trotti A, Foote RL, Schultz C, Thorstad WL, Zhang QE, Le QT, Holsinger FC. Establishing quality indicators for neck dissection: correlating the number of lymph nodes with oncologic outcomes (NRG oncology RTOG 9501 and RTOG 0234). Cancer 2016; 122: 3464-3471
  CrossrefPubMedSearch in Google Scholar
• 68 Böttcher A, Dommerich S, Sander S, Olze H, Stromberger C, Coordes A, Jowett N, Knopke S. Nodal yield of neck dissections and influence on outcome in laryngectomized patients. Eur Arch Oto-Rhino-Laryngology 2016; 273: 3321-3329
  PubMedSearch in Google Scholar
• 69 Ebrahimi A, Clark JR, Amit M, Yen TC, Liao CT, Kowalski LP, Kreppel M, Cernea CR, Bachar G, Villaret AB, Fliss D, Fridman E, Robbins KT, Shah JP, Patel SG, Gil Z. Minimum nodal yield in oral squamous cell carcinoma: defining the standard of care in a multi-center international pooled validation study. Ann Surg Oncol 2014; 21: 3049-3055
  CrossrefPubMedSearch in Google Scholar
• 70 Ebrahimi A, Zhang WJ, Gao K, Clark JR. Nodal yield and survival in oral squamous cancer. Cancer 2011; 117: 2917-2925
  CrossrefPubMedSearch in Google Scholar
• 71 Landheer ML, Therasse P, van de Velde CJ. The importance of quality assurance in surgical oncology. Eur J Surg Oncol 2002; 28: 571e602
  PubMedSearch in Google Scholar
• 72 Velanovich V, Rubinfeld I, Patton Jr JH, Ritz J, Jordan J, Dulchavsky S. Implementation of the national surgical quality improvement program: critical steps to success for surgeons and hospitals. Am J Med Qual 2009; 24: 474e9
  PubMedSearch in Google Scholar
• 73 Birkmeyer JD, Shahian DM, Dimick JB, Finlayson SR, Flum DR, Ko CY, Hall BL. Blueprint for a new American College of Surgeons: National Surgical Quality Improvement Program. J Am Coll Surg 2008; 207: 777e82
  PubMedSearch in Google Scholar
• 74 Lewis CM, Monroe MM, Roberts DB, Hessel AC, Lai SY, Weber RS. An audit in feedback system for effective quality improvement in head and neck surgery: can we become better surgeons?. Cancer 2015; 121: 1581-157
  CrossrefPubMedSearch in Google Scholar
• 75 Liu JC, Kaplon A, Blackman E, Miyamoto C, Savior D, Ragin C. The impact of the multidisciplinary tumor board on head and neck cancer outcomes. Laryngoscope 2019; May 16 [Epub ahead of print]
  CrossrefPubMedSearch in Google Scholar
• 76 Ruhstaller T, Roe H, Thürlimann B, Nicoll JJ. The multidisciplinary meeting: An indispensable aid to communication between different specialities. Eur J Cancer 2006; 42: 2459-2462
  CrossrefPubMedSearch in Google Scholar
• 77 Fleissig A, Jenkins V, Catt S, Fallowfield L. Multidisciplinary teams in cancer care: are they effective in the UK?. Lancet Oncol 2006; 7: 935-943
  CrossrefPubMedSearch in Google Scholar
• 78 Lamb BW, Brown KF, Nagpal K, Vincent C, Green JS, Sevdalis N. Quality of care management decisions by multidisciplinary cancer teams: a systematic review. Ann Surg Oncol 2011; 18: 2116-2125
  CrossrefPubMedSearch in Google Scholar
• 79 Lamb BW, Sevdalis N, Vincent C, Green JSA. Development and evaluation of a checklist to support decision making in cancer multidisciplinary team meetings: MDT-QuIC. Ann Surg Oncol 2012; 19: 1759-6
  PubMedSearch in Google Scholar
• 80 Hollunder S, Herrlinger U, Zipfel M, Schmolders J, Janzen V, Thiesler T, Güresir E, Schröck A, Far F, Pietsch T, Pantelis D, Thomas D, Vornholt S, Ernstmann N, Manser T, Neumann M, Funke B, Schmidt-Wolf IGH. Cross-sectional increase of adherence to multidisciplinary tumor board decisions. BMC Cancer 2018; 18: 936
  CrossrefPubMedSearch in Google Scholar
• 81 Faller H, Koch U, Brähler E, Härter M, Keller M, Schulz H, Wegscheider K, Weis J, Boehncke A, Hund B, Reuter K, Richard M, Sehner S, Szalai C, Wittchen HU, Mehnert A. Satisfaction with information and unmet information needs in men and women with cancer. J Clin Oncol 2016; 10: 62-70
  PubMedSearch in Google Scholar
• 82 Baile WF, Buckmann R, Lenzi R, Glober G, Beale EA, Kudelka AP. SPIKES: a six-step protocol for delivering bad news – application to the patient with cancer. Oncologist 2000; 5: 302-311
  CrossrefPubMedSearch in Google Scholar
• 83 Makoul G. Essential elements of communication in medical encounters: the Kalamazoo consensus statement. Acad Med 2001; 76: 390-393
  CrossrefPubMedSearch in Google Scholar
• 84 Simpson M, Buckman R, Stewart M, Maguire P, Lipkin M, Novack D, Till J. Doctor-patient communication: the Toronto consensus statement. BMJ 1991; 303: 1385-1387
  CrossrefPubMedSearch in Google Scholar
• 85 Albert US, Zemlin C, Hadji P, Ziller V, Kuhler B, Frank-Hahn B, Wagner U, Kalder M. The Impact of Breast Care Nurses on Patients’ Satisfaction, Understanding of the Disease, and Adherence to Adjuvant Endocrine Therapy. Breast Care (Basel). 2011. 6 221-226
  Search in Google Scholar
• 86 Psychoonkologische Diagnostik, Beratung und Behandlung von erwachsenen Krebspatienten https://www.awmf.org/uploads/tx_szleitlinien/032-051OLk_S3_ Psychoonkologische _Beratung_Behandlung_2014-01_abgelaufen.pdf
  PubMed
• 87 Mehnert A, Brähler E, Faller H, Härter M, Keller M, Schulz H, Wegscheider K, Weis J, Boehncke A, Hund B, Reuter K, Richard M, Sehner S, Sommerfeldt S, Szalai C, Wittchen HU, Koch U. Four-week prevalence of mental disorders in patients with cancer across major tumor entities. J Clin Oncol 2014; 32: 3540-3546
  CrossrefPubMedSearch in Google Scholar
• 88 Singer S, Krauss O, Keszte J, Siegl G, Papsdorf K, Severi E, Hauss J, Briest S, Dietz A, Brähler E, Kortmann RD. Predictors of emotional distress in patients with head and neck cancer. Head Neck 2012; 34: 180-187
  CrossrefPubMedSearch in Google Scholar
• 89 Singer S, Dieng S, Wesselmann S. Psycho-oncological care in certified cancer centres – a nationwide analysis in Germany. Psycho-Oncol 2013; 22: 1435-1437
  CrossrefPubMedSearch in Google Scholar
• 90 Kluetz PG, Slagle A, Papadopoulos EJ, Johnson LL, Donoghue M, Kwitkowski VE, Chen WH, Sridhara R, Farrell AT, Keegan P, Kim G, Pazdur R. Focusing on Core Patient-Reported Outcomes in Cancer Clinical Trials: Symptomatic Adverse Events, Physical Function, and Disease-Related Symptoms. Clin Cancer Res 2016; 22: 1553-1558
  CrossrefPubMedSearch in Google Scholar
• 91 Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC. et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993; 85: 365-376
  CrossrefPubMedSearch in Google Scholar
• 92 Cella DF, Tulsky DS, Gray G, Sarafian B, Linn E, Bonomi A, Silberman M, Yellen SB, Winicour P, Brannon J. et al. The Functional Assessment of Cancer Therapy scale: development and validation of the general measure. J Clin Oncol 1993; 11: 570-579
  CrossrefPubMedSearch in Google Scholar
• 93 Duman-Lubberding S, van Uden-Kraan CF, Jansen F, Witte BI, Eerenstein SE, van Weert S, de Bree R, Leemans CR, Verdonck-de Leeuw IM. Durable usage of patient-reported outcome measures in clinical practice to monitor health-related quality of life in head and neck cancer patients. Support Care Cancer 2017; 25: 3775-3783
  CrossrefPubMedSearch in Google Scholar
• 94 Duman-Lubberding S, van Uden-Kraan CF, Jansen F, Witte BI, van der Velden LA, Lacko M, Cuijpers P, Leemans CR, Verdonck-de Leeuw IM. Feasibility of an eHealth application “OncoKompas” to improve personalized survivorship cancer care. Support Care Cancer 2016; 24: 2163-2171
  CrossrefPubMedSearch in Google Scholar
• 95 de Bree R, Verdonck-de Leeuw IM, Keizer AL, Houffelaar A, Leemans CR.. Touch screen computer-assisted health-related quality of life and distress data collection in head and neck cancer patients. Clin Otolaryngol 2008; 33: 138-142
  CrossrefPubMedSearch in Google Scholar
• 96 Zebralla V, Pohle N, Singer S, Neumuth T, Dietz A, Stier-Jarmer M, Boehm A. Introduction of the Screening Tool OncoFunction for Functional Follow-up of Head and Neck Patients. Laryngorhinootol 2016; 95: 118-124
  PubMedSearch in Google Scholar
• 97 Matthijs de Wit L, van Uden-Kraan CF, Lissenberg-Witte BI, Melissant HC, Fleuren MA, Cuijpers P, Verdonck-de Leeuw IM. Adoption and implementation of a web-based self-management application “Oncokompas” in routine cancer care: A national pilot study. Support Care Cancer 2019; 27: 2911-2920
  CrossrefPubMedSearch in Google Scholar
• 98 U.S. Food and drug administration (FDA) . Guidance for industry. Patient-reported outcome measures: use in medical product development to support labeling claims. Federal Regist 2006; 74: 65132-65133
  PubMedSearch in Google Scholar
• 99 Basch E, Deal AM, Dueck AC, Scher HI, Kris MG, Hudis C, Schrag D. Overall Survival Results of a Trial Assessing Patient-Reported Outcomes for Symptom Monitoring During Routine Cancer Treatment. JAMA J Am Med Assoc 2017; 318: 197-198
  CrossrefPubMedSearch in Google Scholar
• 100 Holch JW, Westphalen CB, Hiddemann W, Heinemann V, Jung A, Metzeler KH. Präzisionsonkologie und molekulare und molekulare Tumorboards-Konzepte, Chancen und Herausforderungen. Dtsch Med Wochenschr 2017; 142: 1676-1684
  Thieme ConnectPubMedSearch in Google Scholar
• 101 Li MM, Datto M, Duncavage EJ, Kulkarni S, Lindeman NI, Roy S, Tsimberidou AM, Vnencak-Jones CL, Wolff DJ, Younes A, Nikiforova MN. Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagn 2017; 19: 4-23
  CrossrefPubMedSearch in Google Scholar
• 102 Jennings LJ, Arcila ME, Corless C, Kamel-Reid S, Lubin IM, Pfeifer J, Temple-Smolkin RL, Voelkerding KV, Nikiforova MN. Guidelines for Validation of Next-Generation Sequencing-Based Oncology Panels. J Mol Diagn 2017; 19: 341-365
  CrossrefPubMedSearch in Google Scholar
• 103 Cancer Genome Atlas Network . Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 2015; 517: 576-582
  CrossrefPubMedSearch in Google Scholar
• 104 Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz Jr LA. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015; 372: 2509-2520
  CrossrefPubMedSearch in Google Scholar
• 105 Drilon A, Laetsch TW, Kummar S. Efficacy of Larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med 2018; 378: 731-739
  CrossrefPubMedSearch in Google Scholar
• 106 Knepper TC, Bell GC, Hicks JK, Padron E, Teer JK, Vo TT, Gillis NK, Mason NT, McLeod HL, Walko CM. Key lessons learned from Moffitt’s molecular tumor board: The clinical genomics action committee experience. Oncologist 2017; 22: 144-151
  CrossrefPubMedSearch in Google Scholar
• 107 Schwaederle M, Zhao M, Lee JJ, Lazar V, Leyland-Jones B, Schilsky RL, Mendelsohn J, Kurzrock R. Association of biomarker-based treatment strategies with response rates and progression-free survival in refractory malignant neoplasms: a meta-analysis. Jama Oncol 2016; 2: 1452-1459
  CrossrefPubMedSearch in Google Scholar
• 108 Bryce AH, Egan JB, Borad MJ, Stewart AK, Nowakowski GS, Chanan-Khan A, Patnaik MM, Ansell SM, Banck MS, Robinson SI, Mansfield AS, Klee EW, Oliver GR, McCormick JB, Huneke NE, Tagtow CM, Jenkins RB, Rumilla KM, Kerr SE, Kocher JA, Beck SA, Fernandez-Zapico ME, Farrugia G, Lazaridis KN, McWilliams RR. Experience with precision genomics and tumorboard, indicates frequent target identification, but barriers to delivery. Oncotarget 2017; 8: 27145-27154
  CrossrefPubMedSearch in Google Scholar
• 109 Hirshfield KM, Tolkunov D, Zhong H. Clinical Actionability of Comprehensive Genomic Profiling for Management of Rare or Refractory Cancers. The Oncologist 2016; 21: 1315-1325
  CrossrefPubMedSearch in Google Scholar
• 110 Meric-Bernstam F, Brusco L, Shaw K, Horombe C, Kopetz S, Davies MA, Routbort M, Piha-Paul SA, Janku F, Ueno N, Hong D, De Groot J, Ravi V, Li Y, Luthra R, Patel K, Broaddus R, Mendelsohn J, Mills GB. Feasibility of Large-Scale Genomic Testing to Facilitate Enrollment Onto Genomically Matched Clinical Trials. J Clin Oncol 2015; 33: 2753-2762
  CrossrefPubMedSearch in Google Scholar
• 111 Johnson A, Khotskaya YB, Brusco L, Zeng J, Holla V, Bailey AM, Litzenburger BC, Sanchez N, Shufean MA, Piha-Paul S, Subbiah V, Hong D, Routbort M, Broaddus R, Mills Shaw KR, Mills GB, Mendelsohn J, Meric-Bernstam F. Clinical Use of Precision Oncology Decision Support. JCO Precis. Oncol. 2017; 2017
  PubMedSearch in Google Scholar
• 112 Le Tourneau C, Delord JP, Gonçalves A, Gavoille C, Dubot C, Isambert N, Campone M, Trédan O, Massiani MA, Mauborgne C, Armanet S, Servant N, Bièche I, Bernard V, Gentien D, Jezequel P, Attignon V, Boyault S, Vincent-Salomon A, Servois V, Sablin MP, Kamal M, Paoletti X. SHIVA investigators. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol 2015; 16: 1324-1334
  CrossrefPubMedSearch in Google Scholar
• 113 https://www.cancer.gov/news-events/press-releases/2018/nci-match-first-results
  PubMed
• 114 Schwaederle M, Zhao M, Lee JJ, Eggermont AM, Schilsky RL, Mendelsohn J, Lazar V, Kurzrock R. Impact of Precision Medicine in Diverse Cancers: A Meta-Analysis of Phase II Clinical Trials. J Clin Oncol 2015; 33: 3817-3825
  CrossrefPubMedSearch in Google Scholar
• 115 Marquart J, Chen EY, Prasad V. Estimation of the percentage of US patients with cancer who benefit from genome-driven oncology. JAMA Oncol 2018; 4: 1093-1098
  CrossrefPubMedSearch in Google Scholar
• 116 Rieke DT, Leyvraz S, Burock S, Keilholz U. A comparison of treatment recommendations by molecular tumor boards worldwide. Ann Oncol 2017; 28 Issue suppl_5, mdx363.059
  CrossrefPubMedSearch in Google Scholar
• 117 Kurnit KC, Bailey AM, Zeng J, Johnson AM, Shufean MA, Brusco L, Litzenburger BC, Sánchez NS, Khotskaya YB, Holla V, Simpson A, Mills GB, Mendelsohn J, Bernstam E, Shaw K, Meric-Harada S, Arend R, Dai Q, Levesque JA, Winokur TS, Guo R, Heslin MJ, Nabell L, Nabors LB, Limdi NA, Roth KA, Partridge EE, Siegal GP, Yang ES. Implementation and utilization of the molecular tumor board to guide precision medicine. Oncotarget 2017; 8: 57845-57854
  CrossrefPubMedSearch in Google Scholar
• 118 Mateo J, Chakravarty D, Dienstmann R, Jezdic S, Gonzalez-Perez A, Lopez-Bigas N, Ng CKY, Bedard PL, Tortora G, Douillard JY, Van Allen EM, Schultz N, Swanton C, André F, Pusztai L. A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). Ann Oncol 2018; 29: 1895-1902
  CrossrefPubMedSearch in Google Scholar
• 119 Naredi P, La Quaglia MP. The future of trials in surgical oncology. Nat Rev Clin Oncol 2015; 12: 425e31
  PubMedSearch in Google Scholar
• 120 Ferris RL, Blumenschein Jr G, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Iglesias Docampo LC, Haddad R, Rordorf T, Kiyota N, Tahara M, Monga M, Lynch M, Geese WJ, Kopit J, Shaw JW, Gillison ML. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med 2016; 375: 1856-1867
  CrossrefPubMedSearch in Google Scholar
• 121 Cohen EEW, Soulières D, Le Tourneau C, Dinis J, Licitra L, Ahn MJ, Soria A, Machiels JP, Mach N, Mehra R, Burtness B, Zhang P, Cheng J, Swaby RF, Harrington KJ. KEYNOTE-040 investigators. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet 2019; 393: 156-167
  CrossrefPubMedSearch in Google Scholar
• 122 Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, De Castro Jr. G. et al. Ann Oncol 2018; 29 (Suppl 8): Abstract LBA8_PR
  PubMed
• 123 Schulz KF, Altman DG, Moher D. Group CONSORT. CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. Int J Surg 2011; 9: 672-677
  CrossrefPubMedSearch in Google Scholar
• 124 Clavien PA, Lillemoe KD. A new policy to implement CONSORT guidelines for surgical randomized controlled trials. Ann Surg 2014; 260: 947e8
  PubMedSearch in Google Scholar
• 125 Carlton DA, Kocherginsky M, Langerman AJ. A systematic review of the quality of randomized controlled trials in head and neck oncology surgery. Laryngoscope 2015; 125: 146-152
  CrossrefPubMedSearch in Google Scholar
• 126 Therasse P, De Mulder PH. Quality assurance in medical oncology within the EORTC. European Organisation for Research and Treatment of Cancer. Eur J Cancer 2002; 38 (Suppl 4) 152-154
  CrossrefPubMedSearch in Google Scholar
• 127 Weber DC, Poortmans PM, Hurkmans CW, Aird E, Gulyban A, Fairchild A. Quality assurance for prospective EORTC radiation oncology trials: the challenges of advanced technology in a multicenter international setting. Radiother Oncol 2011; 100: 150-156
  CrossrefPubMedSearch in Google Scholar
• 128 Budiharto T, Musat E, Poortmans P, Hurkmans C, Monti A, Bar-Deroma R, Bernstein Z. Tienhoven Gv, Collette L, Duclos F, Davis B, Aird E; EORTC Radiation Oncology Group. Profile of European radiotherapy departments contributing to the EORTC Radiation Oncology Group (ROG) in the 21^st century. Radiother Oncol 2008; 88: 403-410
  CrossrefPubMedSearch in Google Scholar
• 129 Lefebvre JL, Chevalier D, Luboinski B, Kirkpatrick A, Collette L, Sahmoud T. Larynx preservation in pyriform sinus cancer: preliminary results of a European organization for research and treatment of cancer phase III trial. EORTC Head and Neck Cancer Cooperative group. J Natl Canc Inst 1996; 88: 890e9
  PubMedSearch in Google Scholar
• 130 Evrard S, Audisio R, Poston G, Caballero C, Kataoka K, Fontein D, Collette L, Nakamura K, Fukuda H, Lacombe D. From a comic opera to surcare an open letter to whom clinical research in surgery is a concern: announcing the launch of SURCARE. Ann Surg 2016; 264: 911e2
  PubMedSearch in Google Scholar
• 131 Simon C, Caballero C, Gregoire V, Thurnher D, Koivunen P, Ceruse P, Spriano G, Nicolai P, Licitra L, Machiels JP, Hamoir M, Andry G, Mehanna H, Hunter KD, Dietz A, Leemans CR. Surgical quality assurance in head and neck cancer trials: an EORTC Head and Neck Cancer Group position paper based on the EORTC 1420 ‘Best of’ and 24954 ‘larynx preservation’ study. Eur J Cancer 2018; 103: 69-77
  CrossrefPubMedSearch in Google Scholar
• 132 Wuthrick EJ, Zhang Q, Machtay M, Rosenthal DI, Nguyen-Tan PF, Fortin A, Silverman CL, Raben A, Kim HE, Horwitz EM, Read NE, Harris J, Wu Q, Le QT, Gillison ML. Institutional clinical trial accrual volume and survival of patients with head and neck cancer. J Clin Oncol 2015; 33: 156-164
  PubMedSearch in Google Scholar
• 133 Dietz A, Wichmann G, Kuhnt T, Pfreundner L, Hagen R, Scheich M, Kölbl O, Hautmann MG, Strutz J, Schreiber F, Bockmühl U, Schilling V, Feyer P, de Wit M, Maschmeyer G, Jungehülsing M, Schroeder U, Wollenberg B, Sittel C, Münter M, Lenarz T, Klussmann JP, Guntinas-Lichius O, Rudack C, Eich HT, Foerg T, Preyer S, Westhofen M, Welkoborsky HJ, Esser D, Thurnher D, Remmert S, Sudhoff H, Görner M, Bünzel J, Budach V, Held S, Knödler M, Lordick F, Wiegand S, Vogel K, Boehm A, Flentje M, Keilholz U. 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. Ann Oncol 2018; 29: 2105-2114
  CrossrefPubMedSearch in Google Scholar
• 134 Grègoire V, Lefebvre JL, Licitra L, Felip E. Group . EHNS-ESMO-ESTRO Guidelines Working. Squamous cell carcinoma of the head and neck: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21 (Suppl 5) v184-v186
  CrossrefPubMedSearch in Google Scholar
• 135 Zebralla V, Meuret S, Wiegand S. Monitoring and Evaluation of Late Functional Outcome in Post-treatment Follow-Up in Clinical Routine Setting. Front Oncol 2019; 9: 700
  CrossrefPubMedSearch in Google Scholar
• 136 Zebralla V, Kaminski K, Wichmann G, Dietz A, Wiegand S. Rückkehr in das Erwerbsleben nach kurativer Therapie von Kopf-Hals-Karzinomen. Laryngorhinootologie 2018; 97: 838-845
  Thieme ConnectPubMedSearch in Google Scholar
• 137 Mehnert A. Employment and work-related issues in cancer survivors. Crit Rev Otol Hematol 2011; 77: 109-130
  PubMedSearch in Google Scholar
• 138 Mehnert A, Barth J, Gaspar M, Leibbrand B, Kegel CD, Bootsveld W, Friedrich M, Hartung TJ, Berger D, Koch U. Predictors of early retirement after cancer rehabilitation-a longitudinal study. Eur J Cancer Care (Engl) 2017; 26: 5
  PubMedSearch in Google Scholar
• 139 Böttcher HM, Steimann M, Koch U, Bergelt C. Return to work – experiences and expectations of cancer patients during inpatient rehabilitation. Rehabilitation 2012; 51: 31-38
  Thieme ConnectPubMedSearch in Google Scholar
• 140 Broemer L, Esser P, Koranyi S, Friedrich M, Leuteritz K, Wiegand S, Dietz A, Boehm A, Pabst F, Strauß BM, Guntinas-Lichius O, Mehnert A. Machbarkeit einer Gruppenintervention zur Förderung der Arbeitsfähigkeit für Patienten mit Kopf-Hals-Tumoren. Laryngorhinootol 2019; 98: 175-182
  Thieme ConnectPubMedSearch in Google Scholar

Korrespondenzadresse

• Literatur

• 1 Lohr KN, Schroeder SA. A Strategy for Quality Assurance in Medicare. N Engl J Med 1990; 322: 707-712
  PubMedSearch in Google Scholar
• 2 Bericht zum Krebsgeschehen in Deutschland 2016. Kapitel 4. Folgen von Krebserkrankungen. Robert-Koch-Institut. 2016
  PubMed
• 3 https://www.krebsdaten.de/Krebs/DE/Content/Krebsarten/Mundhoehle_Rachenkrebs/mundhoehle_rachen_node.html;jsessionid=8559195E959168467BBECD37C5E30FB2.1_cid298
  PubMed
• 4 https://www.krebsdaten.de/Krebs/DE/Content/Krebsarten/Kehlkopfkrebs/kehlkopfkrebs_node.html
  PubMed
• 5 Donabedian A. Evaluating the quality of medical care. 1966. Milbank Q 2005; 83: 691-729
  CrossrefPubMedSearch in Google Scholar
• 6 (Muster-)Berufsordnung für die in Deutschland tätigen Ärztinnen und Ärzte - MBO-Ä 1997 – in der Fassung der Beschlüsse des 114. Deutschen Ärztetages 2011 in Kiel https://www.bundesaerztekammer.de/fileadmin/user_upload/downloads/MBO_08_20112.pdf
  PubMed
• 7 Nationaler Krebsplan https://www.bundesgesundheitsministerium.de/fileadmin/ Dateien/5_Publikationen/Praevention/Broschueren/Broschuere_Nationaler_Krebsplan.pdf
  PubMed
• 8 Hamburgisches Krebsregister. Hamburger Krebsdokumentation 1995–1998. Hamburgisches Krebsregister, Hamburg 2001
  PubMed
• 9 Katalinic A, Hense HW, Becker N. Krebsregistrierung in Deutschland. Onkologe 2006; 12: 1084-1093
  CrossrefPubMedSearch in Google Scholar
• 10 Ministerium für Frauen, Arbeit, Gesundheit und Soziales.Morbidität und Mortalität an bösartigen Neubildungen im Saarland 1996 und 1997, Jahresbericht des Saarländischen Krebsregisters. Epidemiologisches Krebsregister Saarland, Saarbrücken. 2000
  PubMedSearch in Google Scholar
• 11 De Angelis R, Sant M, Coleman MP, Francisci S, Baili P, Pierannunzio D, Trama A, Visser O, Brenner H, Ardanaz E, Bielska-Lasota M, Engholm G, Nennecke A, Siesling S, Berrino F, Capocaccia R. EUROCARE-5 Working Group. Cancer survival in Europe 1999–2007 by country and age: results of EUROCARE-5- a population-based study. Lancet Oncol 2014; 15: 23-34
  CrossrefPubMedSearch in Google Scholar
• 12 Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS. Evidence based medicine: what it is and what it isn‘t. BMJ 1996; 312: 71-72
  CrossrefPubMedSearch in Google Scholar
• 13 NCCN Guidelines. Head and neck cancer https://www.nccn.org/store/login/login.aspx?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf
  PubMed
• 14 Koyfman SA, Ismaila N, Holsinger FC. Management of the Neck in Squamous Cell Carcinoma of the Oral Cavity and Oropharynx: ASCO Clinical Practice Guideline Summary. J Oncol Pract 2019; 15: 273-278
  CrossrefPubMedSearch in Google Scholar
• 15 Quon H, Vapiwala N, Forastiere A, Kennedy EB, Adelstein DJ, Boykin H, Califano JA, Holsinger FC, Nussenbaum B, Rosenthal DI, Siu LL, Waldron JN. Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma: American Society of Clinical Oncology Endorsement of the American Society for Radiation Oncology Evidence-Based Clinical Practice Guideline. J Clin Oncol 2017; 35: 4078-4090
  CrossrefPubMedSearch in Google Scholar
• 16 Forastiere AA, Ismaila N, Lewin JS, Nathan CA, Adelstein DJ, Eisbruch A, Fass G, Fisher SG, Laurie SA, Le QT, O'Malley B, Mendenhall WM, Patel S, Pfister DG, Provenzano AF, Weber R, Weinstein GS, Wolf GT. Use of Larynx-Preservation Strategies in the Treatment of Laryngeal Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 2018; 36: 1143-1169
  CrossrefPubMedSearch in Google Scholar
• 17 Grégoire V, Lefebvre JL, Licitra L, Felip E. EHNS-ESMO-ESTRO Guidelines Working Group . Squamous cell carcinoma of the head and neck: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21 Suppl 5 v184-v186
  CrossrefPubMedSearch in Google Scholar
• 18 Chan AT, Grégoire V, Lefebvre JL, Licitra L, Hui EP, Leung SF, Felip E. EHNS–ESMO–ESTRO Guidelines Working Group. Nasopharyngeal cancer: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012; 23 Suppl 7 vii83-vii85
  CrossrefPubMedSearch in Google Scholar
• 19 S3-Leitlinie Diagnostik und Therapie des Mundhöhlenkarzinoms. AWMF-Register-Nummer (007-100OL) Version 2.0 12.2012 https://www.awmf.org/uploads/tx_szleitlinien/007-100OLl_S3_Mundhöhlenkarzinom_122012-122015-abgelaufen.pdf
  PubMed
• 20 S3-Leitlinie Diagnostik, Therapie und Nachsorge des Larynxkarzinoms. Langversion 1.0– Januar 2019, AWMF-Registernummer: 017/076OL https://www.awmf.org/uploads/tx_szleitlinien/017-076OLl_S3_Larynxkarzinom_2019-02.pdf
  PubMed
• 21 Leitlinienprogramm Onkologie https://www.leitlinienprogramm-onkologie.de
  PubMed
• 22 Renninger C. Living guidelines: Anspruch und Wirklichkeit in der Onkologie. https://www.coliquio.de/wissen/onkologie-kompakt-100/Living-Guidelines-100
  PubMed
• 23 Akl EA, Meerpohl JJ, Elliott J, Kahale LA, Schünemann HJ. Living Systematic Review Network. Living systematic reviews: 4. Living guideline recommendations. J Clin Epidemiol 2017; 91: 47-53
  CrossrefPubMedSearch in Google Scholar
• 24 Grimshaw JM, Thomas RE, MacLennan G, Ramsay CR, Vale L, Whitty P, Eccles MP, Matowe L, Shirran L, Wensing M, Dijkstra R, Donaldson C. Effectiveness and efficiency of guideline dissemination and implementation strategies. Health technology assessment 2004; 8: 1-72
  PubMedSearch in Google Scholar
• 25 Swegal WC, Herbert RJ, Eisele DW, Chang J, Bristow RE, Gourin CG. Observed-to-expected ratio for adherence to treatment guidelines as a quality of care indicator for laryngeal cancer. Laryngoscope. 2019; Jun 6 [Epub ahead of print]
  CrossrefPubMedSearch in Google Scholar
• 26 Lewis CM, Nurgalieva Z, Sturgis EM, Lai SY, Weber RS. Improving patient outcomes through multidisciplinary treatment planning conference. Head Neck 2016; 38 Suppl 1 E1820-E1825
  CrossrefPubMedSearch in Google Scholar
• 27 Gourin CG, Herbert RJ, Quon H, Fakhry C, Kiess AP, Eisele DW, Frick KD. Quality of care and short and long-term outcomes of oropharyngeal cancer care in the elderly. Head Neck. 2019; Jul 11 [Epub ahead of print]
  CrossrefPubMedSearch in Google Scholar
• 28 Alle onkologischen S3-Leitlinien – jetzt auch als App! Forum 2019; 34: 130
  PubMed
• 29 McGlynn EA, Asch SM. Developing a clinical performance measure. Am J Prev Med 1998; 14 (3 Suppl) 14-21
  CrossrefPubMedSearch in Google Scholar
• 30 Sens B, Fischer B, Bastek A, Eckardt J, Kaczmarek D, Paschen U, Pietsch B, Rath S, Ruprecht T, Thomeczek C, Veit C, Wenzlaff P. Begriffe und Konzepte des Qualitätsmanagements – 3. Auflage. . GMS Med Inform Biom Epidemiol 2007; 3: Doc05 http://www.egms.de/en/journals/mibe/2007- 3/mibe000053.shtml
  PubMedSearch in Google Scholar
• 31 Standard Operating Procedures (SOPs) http://www.ccc-netzwerk.de/arbeits-gruppen/standard-operating-procedures.html
  PubMed
• 32 Heimpl H. Zur Bedeutung nationaler und lokaler Leitlinien für ärztliche Entscheidungen. Medizinische Klinik 2003; 98: 226-230
  CrossrefPubMedSearch in Google Scholar
• 33 Cramer JD, Speedy SE, Ferris RL, Rademaker AW, Patel UA, Samant S. National evaluation of multidisciplinary quality metrics for head and neck cancer. Cancer 2017; 123: 4372-4381
  CrossrefPubMedSearch in Google Scholar
• 34 Mensah J, Graeven U, Wesselmann S. Nationales Zertifizierungsprogramm Krebs. Der Onkologe 2017; 23: 711-718
  CrossrefPubMedSearch in Google Scholar
• 35 Klauber J, Geraedts M, Friedrich J, Wasem J. Hrsg Krankenhaus-Report 2019. Das digitale Krankenhaus. Springer; Berlin Heidelberg:
• 36 Deutsche Krebsgesellschaft startet Pilotprojekt zur ärztlichen Zweitmeinung. Forum. 2019 34. 230
  PubMedSearch in Google Scholar
• 37 Adam H, Sibert NT, Bruns J, Wesselmann S. Krebspatienten qualitätsgesichert, multidisziplinär und evidenzbasiert versorgen: das Zertifizierungssystem der Deutschen Krebsgesellschaft. BARMER Gesundheitswesen aktuell 2018; 136-155
  PubMedSearch in Google Scholar
• 38 Kennzahlenauswertung 2019. Jahresbericht der zertifizierten Kopf-Hals-Tumorzentren https://www.onkozert.de/wordpress/wp-content/uploads/2019/05/khtz_jahresbericht-2019-A1_190521.pdf?v=15484791
  PubMed
• 39 Prognos 2018: Endbericht „Nutzen, Mehraufwand und Finanzierung von Onkologischen Spitzenzentren, Onkologischen Zentren und Organkrebszentren“. Im Auftrag der Deutschen Krebshilfe und der Deutschen Krebsgesellschaft https://www.krebshilfe.de/fileadmin/Downloads/PDFs/Stellungnahmen/Prognos_Endbericht_Deutsche_Krebshilfe.pdf
  PubMed
• 40 https://www.onkozert.de/organ/kopf-hals/
  PubMed
• 41 Kowalski C, Graeven U, von Kalle C, Lang H, Beckmann MW, Blohmer JU, Burchardt M, Ehrenfeld M, Fichtner J, Grabbe S, Hoffmann H, Iro H, Post S, Scharl A, Schlegel U, Seufferlein T, Stummer W, Ukena D, Ferencz J, Wesselmann S. Shifting cancer care towards multidisciplinarity: the cancer center certification program of the German cancer society. BMC Cancer 2017; 17: 850
  CrossrefPubMedSearch in Google Scholar
• 42 Oeser A, Gaebel J, Dietz A, Wiegand S, Oeltze-Jafra S. Information architecture for a patient-specific dashboard in head and neck tumor boards. Int J Comput Assist Radiol Surg 2018; 13: 1283-1290
  CrossrefPubMedSearch in Google Scholar
• 43 Wiegand S, Dietz A. Vor- und Nachteile eines Zertifizierungsverfahrens aus Sicht eines Kopf-Hals-Tumorzentrums. Der Onkologe 2017; 23: 719-726
  CrossrefPubMedSearch in Google Scholar
• 44 Luft HS, Bunker JP, Enthoven AC. Should operations be regionalized? The empirical relation between surgical volume and mortality. NEJM 1979; 301: 1364-1369
  CrossrefPubMedSearch in Google Scholar
• 45 Begg CB, Cramer LD, Hoskins WJ, Brennan MF. Impact of hospital volume on operative mortality for major cancer surgery. JAMA 1998; 280: 1747-1751
  CrossrefPubMedSearch in Google Scholar
• 46 Birkmeyer JD, Siewers AE, Finlayson EV, Stukel TA, Lucas FL, Batista I, Welch HG, Wennberg DE. Hospital volume and surgical mortality in the United States. NEJM 2002; 346: 1128-1137
  CrossrefPubMedSearch in Google Scholar
• 47 Eskander A, Merdad M, Irish JC, Hall SF, Groome PA, Freeman JL, Urbach DR, Goldstein DP. Volume-outcome associations in head and neck cancer treatment: a systematic review and meta-analysis. Head Neck 2014; 36: 1820-1834
  CrossrefPubMedSearch in Google Scholar
• 48 Eskander A, Irish J, Groome PA, Freeman J, Gullane P, Gilbert R, Hall SF, Urbach DR, Goldstein DP. Volume-outcome relationships for head and neck cancer surgery in a universal health care system. Laryngoscope 2014; 124: 2081-2088
  CrossrefPubMedSearch in Google Scholar
• 49 Redmann AJ, Yuen SN, Von Allmen D, Rothstein A, Tang A, Breen J, Collar R. Does Surgical Volume and Complexity Affect Cost and Mortality in Otolaryngology-Head and Neck Surgery?. Otolaryngol Head Neck Surg 2019; 16: 194599819861524
  PubMedSearch in Google Scholar
• 50 Cheung MC, Koniaris LG, Perez EA, Molina MA, Goodwin WJ, Salloum RM. Impact of hospital volume on surgical outcome for head and neck cancer. Ann Surg Oncol 2009; 16: 1001-1009
  CrossrefPubMedSearch in Google Scholar
• 51 Lassig AA, Joseph AM, Lindgren BR, Fernandes P, Cooper S, Schotzko C, Khariwala S, Reynolds M, Yueh B. The effect of treating institution on outcomes in head and neck cancer. Otolaryngol Head Neck Surg 2012; 147: 1083-1092
  CrossrefPubMedSearch in Google Scholar
• 52 Chen AY, Fedewa S, Pavluck A, Ward EM. Improved survival is associated with treatment at high-volume teaching facilities for patients with advanced stage laryngeal cancer. Cancer 2010; 116: 4744-4752
  CrossrefPubMedSearch in Google Scholar
• 53 Grover S, Swisher-McClure S, Mitra N, Li J, Cohen RB, Ahn PH, Lukens JN, Chalian AA, Weinstein GS, O'Malley Jr BW, Lin A. Total laryngectomy versus larynx preservation for T4a larynx cancer: Patterns of care and survival outcomes. Int J Radiat Oncol Biol Phys 2015; 92: 594-601
  CrossrefPubMedSearch in Google Scholar
• 54 Luft HS, Hunt SS, Maerki SC. The volume-outcome relationship: practice-makes-perfect or selective-referral patterns?. Health Serv Res 1987; 22: 157-182
  PubMedSearch in Google Scholar
• 55 Markar SR, Karthikesalingam A, Thrumurthy S, Low DE. Volume-outcome relationship in surgery for esophageal malignancy: systematic review and meta-analysis 2000-2011. J Gastrointest Surg 2012; 16: 1055-1063
  CrossrefPubMedSearch in Google Scholar
• 56 Hoffmann H, Passlick B, Ukena D, Wesselmann S. Chirurgische Therapie des Lungenkarzinoms: Argumente für die Behandlung in großen Zentren. Zentralbl Chir 2019; 144: 62-70
  Thieme ConnectPubMedSearch in Google Scholar
• 57 Trautmann F, Reissfelder C, Pecqueux M, Weitz J, Schmitt J. Evidence-based quality standards improve prognosis in colon cancer care. Eur J Surg Oncol 2018; 44: 1324-1330
  CrossrefPubMedSearch in Google Scholar
• 58 Völkel V, Draeger T, Gerken M, Fürst A, Klinkhammer-Schalke M. Langzeitüberleben von Patienten mit Kolon und Rektumkarzinomen: Ein Vergleich von Darmkrebszentren und nicht zertifizierten Krankenhäusern. Gesundheitswesen 2018; Apr 19 [Epub ahead of print]
  Thieme ConnectPubMedSearch in Google Scholar
• 59 Lin CC, Lin HC. Effects of surgeon and hospital volume on 5-year survival rates following oral cancer resections: the experience of an Asian country. Surgery 2008; 143: 343-351
  CrossrefPubMedSearch in Google Scholar
• 60 Broome M, Juilland N, Litzistorf Y, Monnier Y, Sandu K, Pasche P, Plinkert PK, Federspil PA, Simon C. Factors Influencing the Incidence of Severe Complications in Head and Neck Free Flap Reconstructions. Plast Reconstr Surg Glob Open 2016; 4: e1013
  CrossrefPubMedSearch in Google Scholar
• 61 Morton RP, Gray L, Tandon DA, Izzard M, McIvor NP. Efficacy of neck dissection: are surgical volumes important?. Laryngoscope 2009; 119: 1147-1152
  CrossrefPubMedSearch in Google Scholar
• 62 Cheraghlou S, Otremba M, Kuo Yu P, Agogo GO, Hersey D, Judson BL. Prognostic Value of Lymph Node Yield and Density in Head and Neck Malignancies. Otolaryngol Head Neck Surg 2018; 158: 1016-1023
  CrossrefPubMedSearch in Google Scholar
• 63 de Kort WWB, Maas SLN. Van Es RJJ, Willems SM. Prognostic value of the nodal yield in head and neck squamous cell carcinoma: A systematic review. Head Neck 2019; 41: 2801-2810
  CrossrefPubMedSearch in Google Scholar
• 64 Merz S, Timmesfeld N, Stuck BA, Wiegand S. Impact of Lymph Node Yield on Outcome of Patients with Head and Neck Cancer and pN0 Neck. Anticancer Res 2018; 38: 5347-5350
  PubMedSearch in Google Scholar
• 65 Son H-J, Roh J-L, Cho K-J, Choi S-H, Nam SY, Kim SY. Nodal factors predictive of recurrence and survival in patients with oral cavity squamous cell carcinoma. Clin Otolaryngol 2017; 43: 470-476
  PubMedSearch in Google Scholar
• 66 Divi V, Chen MM, Nussenbaum B, Rhoads KF, Sirjani DB, Holsinger FC, Shah JL, Hara W. Lymph node count from neck dissection predicts mortality in head and neck cancer. J Clin Oncol 2016; 34: 3892-3897
  CrossrefPubMedSearch in Google Scholar
• 67 Divi V, Harris J, Harari PM, Cooper JS, McHugh J, Bell D, Sturgis EM, Cmelak AJ, Suntharalingam M, Raben D, Kim H, Spencer SA, Laramore GE, Trotti A, Foote RL, Schultz C, Thorstad WL, Zhang QE, Le QT, Holsinger FC. Establishing quality indicators for neck dissection: correlating the number of lymph nodes with oncologic outcomes (NRG oncology RTOG 9501 and RTOG 0234). Cancer 2016; 122: 3464-3471
  CrossrefPubMedSearch in Google Scholar
• 68 Böttcher A, Dommerich S, Sander S, Olze H, Stromberger C, Coordes A, Jowett N, Knopke S. Nodal yield of neck dissections and influence on outcome in laryngectomized patients. Eur Arch Oto-Rhino-Laryngology 2016; 273: 3321-3329
  PubMedSearch in Google Scholar
• 69 Ebrahimi A, Clark JR, Amit M, Yen TC, Liao CT, Kowalski LP, Kreppel M, Cernea CR, Bachar G, Villaret AB, Fliss D, Fridman E, Robbins KT, Shah JP, Patel SG, Gil Z. Minimum nodal yield in oral squamous cell carcinoma: defining the standard of care in a multi-center international pooled validation study. Ann Surg Oncol 2014; 21: 3049-3055
  CrossrefPubMedSearch in Google Scholar
• 70 Ebrahimi A, Zhang WJ, Gao K, Clark JR. Nodal yield and survival in oral squamous cancer. Cancer 2011; 117: 2917-2925
  CrossrefPubMedSearch in Google Scholar
• 71 Landheer ML, Therasse P, van de Velde CJ. The importance of quality assurance in surgical oncology. Eur J Surg Oncol 2002; 28: 571e602
  PubMedSearch in Google Scholar
• 72 Velanovich V, Rubinfeld I, Patton Jr JH, Ritz J, Jordan J, Dulchavsky S. Implementation of the national surgical quality improvement program: critical steps to success for surgeons and hospitals. Am J Med Qual 2009; 24: 474e9
  PubMedSearch in Google Scholar
• 73 Birkmeyer JD, Shahian DM, Dimick JB, Finlayson SR, Flum DR, Ko CY, Hall BL. Blueprint for a new American College of Surgeons: National Surgical Quality Improvement Program. J Am Coll Surg 2008; 207: 777e82
  PubMedSearch in Google Scholar
• 74 Lewis CM, Monroe MM, Roberts DB, Hessel AC, Lai SY, Weber RS. An audit in feedback system for effective quality improvement in head and neck surgery: can we become better surgeons?. Cancer 2015; 121: 1581-157
  CrossrefPubMedSearch in Google Scholar
• 75 Liu JC, Kaplon A, Blackman E, Miyamoto C, Savior D, Ragin C. The impact of the multidisciplinary tumor board on head and neck cancer outcomes. Laryngoscope 2019; May 16 [Epub ahead of print]
  CrossrefPubMedSearch in Google Scholar
• 76 Ruhstaller T, Roe H, Thürlimann B, Nicoll JJ. The multidisciplinary meeting: An indispensable aid to communication between different specialities. Eur J Cancer 2006; 42: 2459-2462
  CrossrefPubMedSearch in Google Scholar
• 77 Fleissig A, Jenkins V, Catt S, Fallowfield L. Multidisciplinary teams in cancer care: are they effective in the UK?. Lancet Oncol 2006; 7: 935-943
  CrossrefPubMedSearch in Google Scholar
• 78 Lamb BW, Brown KF, Nagpal K, Vincent C, Green JS, Sevdalis N. Quality of care management decisions by multidisciplinary cancer teams: a systematic review. Ann Surg Oncol 2011; 18: 2116-2125
  CrossrefPubMedSearch in Google Scholar
• 79 Lamb BW, Sevdalis N, Vincent C, Green JSA. Development and evaluation of a checklist to support decision making in cancer multidisciplinary team meetings: MDT-QuIC. Ann Surg Oncol 2012; 19: 1759-6
  PubMedSearch in Google Scholar
• 80 Hollunder S, Herrlinger U, Zipfel M, Schmolders J, Janzen V, Thiesler T, Güresir E, Schröck A, Far F, Pietsch T, Pantelis D, Thomas D, Vornholt S, Ernstmann N, Manser T, Neumann M, Funke B, Schmidt-Wolf IGH. Cross-sectional increase of adherence to multidisciplinary tumor board decisions. BMC Cancer 2018; 18: 936
  CrossrefPubMedSearch in Google Scholar
• 81 Faller H, Koch U, Brähler E, Härter M, Keller M, Schulz H, Wegscheider K, Weis J, Boehncke A, Hund B, Reuter K, Richard M, Sehner S, Szalai C, Wittchen HU, Mehnert A. Satisfaction with information and unmet information needs in men and women with cancer. J Clin Oncol 2016; 10: 62-70
  PubMedSearch in Google Scholar
• 82 Baile WF, Buckmann R, Lenzi R, Glober G, Beale EA, Kudelka AP. SPIKES: a six-step protocol for delivering bad news – application to the patient with cancer. Oncologist 2000; 5: 302-311
  CrossrefPubMedSearch in Google Scholar
• 83 Makoul G. Essential elements of communication in medical encounters: the Kalamazoo consensus statement. Acad Med 2001; 76: 390-393
  CrossrefPubMedSearch in Google Scholar
• 84 Simpson M, Buckman R, Stewart M, Maguire P, Lipkin M, Novack D, Till J. Doctor-patient communication: the Toronto consensus statement. BMJ 1991; 303: 1385-1387
  CrossrefPubMedSearch in Google Scholar
• 85 Albert US, Zemlin C, Hadji P, Ziller V, Kuhler B, Frank-Hahn B, Wagner U, Kalder M. The Impact of Breast Care Nurses on Patients’ Satisfaction, Understanding of the Disease, and Adherence to Adjuvant Endocrine Therapy. Breast Care (Basel). 2011. 6 221-226
  Search in Google Scholar
• 86 Psychoonkologische Diagnostik, Beratung und Behandlung von erwachsenen Krebspatienten https://www.awmf.org/uploads/tx_szleitlinien/032-051OLk_S3_ Psychoonkologische _Beratung_Behandlung_2014-01_abgelaufen.pdf
  PubMed
• 87 Mehnert A, Brähler E, Faller H, Härter M, Keller M, Schulz H, Wegscheider K, Weis J, Boehncke A, Hund B, Reuter K, Richard M, Sehner S, Sommerfeldt S, Szalai C, Wittchen HU, Koch U. Four-week prevalence of mental disorders in patients with cancer across major tumor entities. J Clin Oncol 2014; 32: 3540-3546
  CrossrefPubMedSearch in Google Scholar
• 88 Singer S, Krauss O, Keszte J, Siegl G, Papsdorf K, Severi E, Hauss J, Briest S, Dietz A, Brähler E, Kortmann RD. Predictors of emotional distress in patients with head and neck cancer. Head Neck 2012; 34: 180-187
  CrossrefPubMedSearch in Google Scholar
• 89 Singer S, Dieng S, Wesselmann S. Psycho-oncological care in certified cancer centres – a nationwide analysis in Germany. Psycho-Oncol 2013; 22: 1435-1437
  CrossrefPubMedSearch in Google Scholar
• 90 Kluetz PG, Slagle A, Papadopoulos EJ, Johnson LL, Donoghue M, Kwitkowski VE, Chen WH, Sridhara R, Farrell AT, Keegan P, Kim G, Pazdur R. Focusing on Core Patient-Reported Outcomes in Cancer Clinical Trials: Symptomatic Adverse Events, Physical Function, and Disease-Related Symptoms. Clin Cancer Res 2016; 22: 1553-1558
  CrossrefPubMedSearch in Google Scholar
• 91 Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC. et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993; 85: 365-376
  CrossrefPubMedSearch in Google Scholar
• 92 Cella DF, Tulsky DS, Gray G, Sarafian B, Linn E, Bonomi A, Silberman M, Yellen SB, Winicour P, Brannon J. et al. The Functional Assessment of Cancer Therapy scale: development and validation of the general measure. J Clin Oncol 1993; 11: 570-579
  CrossrefPubMedSearch in Google Scholar
• 93 Duman-Lubberding S, van Uden-Kraan CF, Jansen F, Witte BI, Eerenstein SE, van Weert S, de Bree R, Leemans CR, Verdonck-de Leeuw IM. Durable usage of patient-reported outcome measures in clinical practice to monitor health-related quality of life in head and neck cancer patients. Support Care Cancer 2017; 25: 3775-3783
  CrossrefPubMedSearch in Google Scholar
• 94 Duman-Lubberding S, van Uden-Kraan CF, Jansen F, Witte BI, van der Velden LA, Lacko M, Cuijpers P, Leemans CR, Verdonck-de Leeuw IM. Feasibility of an eHealth application “OncoKompas” to improve personalized survivorship cancer care. Support Care Cancer 2016; 24: 2163-2171
  CrossrefPubMedSearch in Google Scholar
• 95 de Bree R, Verdonck-de Leeuw IM, Keizer AL, Houffelaar A, Leemans CR.. Touch screen computer-assisted health-related quality of life and distress data collection in head and neck cancer patients. Clin Otolaryngol 2008; 33: 138-142
  CrossrefPubMedSearch in Google Scholar
• 96 Zebralla V, Pohle N, Singer S, Neumuth T, Dietz A, Stier-Jarmer M, Boehm A. Introduction of the Screening Tool OncoFunction for Functional Follow-up of Head and Neck Patients. Laryngorhinootol 2016; 95: 118-124
  PubMedSearch in Google Scholar
• 97 Matthijs de Wit L, van Uden-Kraan CF, Lissenberg-Witte BI, Melissant HC, Fleuren MA, Cuijpers P, Verdonck-de Leeuw IM. Adoption and implementation of a web-based self-management application “Oncokompas” in routine cancer care: A national pilot study. Support Care Cancer 2019; 27: 2911-2920
  CrossrefPubMedSearch in Google Scholar
• 98 U.S. Food and drug administration (FDA) . Guidance for industry. Patient-reported outcome measures: use in medical product development to support labeling claims. Federal Regist 2006; 74: 65132-65133
  PubMedSearch in Google Scholar
• 99 Basch E, Deal AM, Dueck AC, Scher HI, Kris MG, Hudis C, Schrag D. Overall Survival Results of a Trial Assessing Patient-Reported Outcomes for Symptom Monitoring During Routine Cancer Treatment. JAMA J Am Med Assoc 2017; 318: 197-198
  CrossrefPubMedSearch in Google Scholar
• 100 Holch JW, Westphalen CB, Hiddemann W, Heinemann V, Jung A, Metzeler KH. Präzisionsonkologie und molekulare und molekulare Tumorboards-Konzepte, Chancen und Herausforderungen. Dtsch Med Wochenschr 2017; 142: 1676-1684
  Thieme ConnectPubMedSearch in Google Scholar
• 101 Li MM, Datto M, Duncavage EJ, Kulkarni S, Lindeman NI, Roy S, Tsimberidou AM, Vnencak-Jones CL, Wolff DJ, Younes A, Nikiforova MN. Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagn 2017; 19: 4-23
  CrossrefPubMedSearch in Google Scholar
• 102 Jennings LJ, Arcila ME, Corless C, Kamel-Reid S, Lubin IM, Pfeifer J, Temple-Smolkin RL, Voelkerding KV, Nikiforova MN. Guidelines for Validation of Next-Generation Sequencing-Based Oncology Panels. J Mol Diagn 2017; 19: 341-365
  CrossrefPubMedSearch in Google Scholar
• 103 Cancer Genome Atlas Network . Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 2015; 517: 576-582
  CrossrefPubMedSearch in Google Scholar
• 104 Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz Jr LA. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015; 372: 2509-2520
  CrossrefPubMedSearch in Google Scholar
• 105 Drilon A, Laetsch TW, Kummar S. Efficacy of Larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med 2018; 378: 731-739
  CrossrefPubMedSearch in Google Scholar
• 106 Knepper TC, Bell GC, Hicks JK, Padron E, Teer JK, Vo TT, Gillis NK, Mason NT, McLeod HL, Walko CM. Key lessons learned from Moffitt’s molecular tumor board: The clinical genomics action committee experience. Oncologist 2017; 22: 144-151
  CrossrefPubMedSearch in Google Scholar
• 107 Schwaederle M, Zhao M, Lee JJ, Lazar V, Leyland-Jones B, Schilsky RL, Mendelsohn J, Kurzrock R. Association of biomarker-based treatment strategies with response rates and progression-free survival in refractory malignant neoplasms: a meta-analysis. Jama Oncol 2016; 2: 1452-1459
  CrossrefPubMedSearch in Google Scholar
• 108 Bryce AH, Egan JB, Borad MJ, Stewart AK, Nowakowski GS, Chanan-Khan A, Patnaik MM, Ansell SM, Banck MS, Robinson SI, Mansfield AS, Klee EW, Oliver GR, McCormick JB, Huneke NE, Tagtow CM, Jenkins RB, Rumilla KM, Kerr SE, Kocher JA, Beck SA, Fernandez-Zapico ME, Farrugia G, Lazaridis KN, McWilliams RR. Experience with precision genomics and tumorboard, indicates frequent target identification, but barriers to delivery. Oncotarget 2017; 8: 27145-27154
  CrossrefPubMedSearch in Google Scholar
• 109 Hirshfield KM, Tolkunov D, Zhong H. Clinical Actionability of Comprehensive Genomic Profiling for Management of Rare or Refractory Cancers. The Oncologist 2016; 21: 1315-1325
  CrossrefPubMedSearch in Google Scholar
• 110 Meric-Bernstam F, Brusco L, Shaw K, Horombe C, Kopetz S, Davies MA, Routbort M, Piha-Paul SA, Janku F, Ueno N, Hong D, De Groot J, Ravi V, Li Y, Luthra R, Patel K, Broaddus R, Mendelsohn J, Mills GB. Feasibility of Large-Scale Genomic Testing to Facilitate Enrollment Onto Genomically Matched Clinical Trials. J Clin Oncol 2015; 33: 2753-2762
  CrossrefPubMedSearch in Google Scholar
• 111 Johnson A, Khotskaya YB, Brusco L, Zeng J, Holla V, Bailey AM, Litzenburger BC, Sanchez N, Shufean MA, Piha-Paul S, Subbiah V, Hong D, Routbort M, Broaddus R, Mills Shaw KR, Mills GB, Mendelsohn J, Meric-Bernstam F. Clinical Use of Precision Oncology Decision Support. JCO Precis. Oncol. 2017; 2017
  PubMedSearch in Google Scholar
• 112 Le Tourneau C, Delord JP, Gonçalves A, Gavoille C, Dubot C, Isambert N, Campone M, Trédan O, Massiani MA, Mauborgne C, Armanet S, Servant N, Bièche I, Bernard V, Gentien D, Jezequel P, Attignon V, Boyault S, Vincent-Salomon A, Servois V, Sablin MP, Kamal M, Paoletti X. SHIVA investigators. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol 2015; 16: 1324-1334
  CrossrefPubMedSearch in Google Scholar
• 113 https://www.cancer.gov/news-events/press-releases/2018/nci-match-first-results
  PubMed
• 114 Schwaederle M, Zhao M, Lee JJ, Eggermont AM, Schilsky RL, Mendelsohn J, Lazar V, Kurzrock R. Impact of Precision Medicine in Diverse Cancers: A Meta-Analysis of Phase II Clinical Trials. J Clin Oncol 2015; 33: 3817-3825
  CrossrefPubMedSearch in Google Scholar
• 115 Marquart J, Chen EY, Prasad V. Estimation of the percentage of US patients with cancer who benefit from genome-driven oncology. JAMA Oncol 2018; 4: 1093-1098
  CrossrefPubMedSearch in Google Scholar
• 116 Rieke DT, Leyvraz S, Burock S, Keilholz U. A comparison of treatment recommendations by molecular tumor boards worldwide. Ann Oncol 2017; 28 Issue suppl_5, mdx363.059
  CrossrefPubMedSearch in Google Scholar
• 117 Kurnit KC, Bailey AM, Zeng J, Johnson AM, Shufean MA, Brusco L, Litzenburger BC, Sánchez NS, Khotskaya YB, Holla V, Simpson A, Mills GB, Mendelsohn J, Bernstam E, Shaw K, Meric-Harada S, Arend R, Dai Q, Levesque JA, Winokur TS, Guo R, Heslin MJ, Nabell L, Nabors LB, Limdi NA, Roth KA, Partridge EE, Siegal GP, Yang ES. Implementation and utilization of the molecular tumor board to guide precision medicine. Oncotarget 2017; 8: 57845-57854
  CrossrefPubMedSearch in Google Scholar
• 118 Mateo J, Chakravarty D, Dienstmann R, Jezdic S, Gonzalez-Perez A, Lopez-Bigas N, Ng CKY, Bedard PL, Tortora G, Douillard JY, Van Allen EM, Schultz N, Swanton C, André F, Pusztai L. A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). Ann Oncol 2018; 29: 1895-1902
  CrossrefPubMedSearch in Google Scholar
• 119 Naredi P, La Quaglia MP. The future of trials in surgical oncology. Nat Rev Clin Oncol 2015; 12: 425e31
  PubMedSearch in Google Scholar
• 120 Ferris RL, Blumenschein Jr G, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Iglesias Docampo LC, Haddad R, Rordorf T, Kiyota N, Tahara M, Monga M, Lynch M, Geese WJ, Kopit J, Shaw JW, Gillison ML. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med 2016; 375: 1856-1867
  CrossrefPubMedSearch in Google Scholar
• 121 Cohen EEW, Soulières D, Le Tourneau C, Dinis J, Licitra L, Ahn MJ, Soria A, Machiels JP, Mach N, Mehra R, Burtness B, Zhang P, Cheng J, Swaby RF, Harrington KJ. KEYNOTE-040 investigators. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet 2019; 393: 156-167
  CrossrefPubMedSearch in Google Scholar
• 122 Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, De Castro Jr. G. et al. Ann Oncol 2018; 29 (Suppl 8): Abstract LBA8_PR
  PubMed
• 123 Schulz KF, Altman DG, Moher D. Group CONSORT. CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. Int J Surg 2011; 9: 672-677
  CrossrefPubMedSearch in Google Scholar
• 124 Clavien PA, Lillemoe KD. A new policy to implement CONSORT guidelines for surgical randomized controlled trials. Ann Surg 2014; 260: 947e8
  PubMedSearch in Google Scholar
• 125 Carlton DA, Kocherginsky M, Langerman AJ. A systematic review of the quality of randomized controlled trials in head and neck oncology surgery. Laryngoscope 2015; 125: 146-152
  CrossrefPubMedSearch in Google Scholar
• 126 Therasse P, De Mulder PH. Quality assurance in medical oncology within the EORTC. European Organisation for Research and Treatment of Cancer. Eur J Cancer 2002; 38 (Suppl 4) 152-154
  CrossrefPubMedSearch in Google Scholar
• 127 Weber DC, Poortmans PM, Hurkmans CW, Aird E, Gulyban A, Fairchild A. Quality assurance for prospective EORTC radiation oncology trials: the challenges of advanced technology in a multicenter international setting. Radiother Oncol 2011; 100: 150-156
  CrossrefPubMedSearch in Google Scholar
• 128 Budiharto T, Musat E, Poortmans P, Hurkmans C, Monti A, Bar-Deroma R, Bernstein Z. Tienhoven Gv, Collette L, Duclos F, Davis B, Aird E; EORTC Radiation Oncology Group. Profile of European radiotherapy departments contributing to the EORTC Radiation Oncology Group (ROG) in the 21^st century. Radiother Oncol 2008; 88: 403-410
  CrossrefPubMedSearch in Google Scholar
• 129 Lefebvre JL, Chevalier D, Luboinski B, Kirkpatrick A, Collette L, Sahmoud T. Larynx preservation in pyriform sinus cancer: preliminary results of a European organization for research and treatment of cancer phase III trial. EORTC Head and Neck Cancer Cooperative group. J Natl Canc Inst 1996; 88: 890e9
  PubMedSearch in Google Scholar
• 130 Evrard S, Audisio R, Poston G, Caballero C, Kataoka K, Fontein D, Collette L, Nakamura K, Fukuda H, Lacombe D. From a comic opera to surcare an open letter to whom clinical research in surgery is a concern: announcing the launch of SURCARE. Ann Surg 2016; 264: 911e2
  PubMedSearch in Google Scholar
• 131 Simon C, Caballero C, Gregoire V, Thurnher D, Koivunen P, Ceruse P, Spriano G, Nicolai P, Licitra L, Machiels JP, Hamoir M, Andry G, Mehanna H, Hunter KD, Dietz A, Leemans CR. Surgical quality assurance in head and neck cancer trials: an EORTC Head and Neck Cancer Group position paper based on the EORTC 1420 ‘Best of’ and 24954 ‘larynx preservation’ study. Eur J Cancer 2018; 103: 69-77
  CrossrefPubMedSearch in Google Scholar
• 132 Wuthrick EJ, Zhang Q, Machtay M, Rosenthal DI, Nguyen-Tan PF, Fortin A, Silverman CL, Raben A, Kim HE, Horwitz EM, Read NE, Harris J, Wu Q, Le QT, Gillison ML. Institutional clinical trial accrual volume and survival of patients with head and neck cancer. J Clin Oncol 2015; 33: 156-164
  PubMedSearch in Google Scholar
• 133 Dietz A, Wichmann G, Kuhnt T, Pfreundner L, Hagen R, Scheich M, Kölbl O, Hautmann MG, Strutz J, Schreiber F, Bockmühl U, Schilling V, Feyer P, de Wit M, Maschmeyer G, Jungehülsing M, Schroeder U, Wollenberg B, Sittel C, Münter M, Lenarz T, Klussmann JP, Guntinas-Lichius O, Rudack C, Eich HT, Foerg T, Preyer S, Westhofen M, Welkoborsky HJ, Esser D, Thurnher D, Remmert S, Sudhoff H, Görner M, Bünzel J, Budach V, Held S, Knödler M, Lordick F, Wiegand S, Vogel K, Boehm A, Flentje M, Keilholz U. 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. Ann Oncol 2018; 29: 2105-2114
  CrossrefPubMedSearch in Google Scholar
• 134 Grègoire V, Lefebvre JL, Licitra L, Felip E. Group . EHNS-ESMO-ESTRO Guidelines Working. Squamous cell carcinoma of the head and neck: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21 (Suppl 5) v184-v186
  CrossrefPubMedSearch in Google Scholar
• 135 Zebralla V, Meuret S, Wiegand S. Monitoring and Evaluation of Late Functional Outcome in Post-treatment Follow-Up in Clinical Routine Setting. Front Oncol 2019; 9: 700
  CrossrefPubMedSearch in Google Scholar
• 136 Zebralla V, Kaminski K, Wichmann G, Dietz A, Wiegand S. Rückkehr in das Erwerbsleben nach kurativer Therapie von Kopf-Hals-Karzinomen. Laryngorhinootologie 2018; 97: 838-845
  Thieme ConnectPubMedSearch in Google Scholar
• 137 Mehnert A. Employment and work-related issues in cancer survivors. Crit Rev Otol Hematol 2011; 77: 109-130
  PubMedSearch in Google Scholar
• 138 Mehnert A, Barth J, Gaspar M, Leibbrand B, Kegel CD, Bootsveld W, Friedrich M, Hartung TJ, Berger D, Koch U. Predictors of early retirement after cancer rehabilitation-a longitudinal study. Eur J Cancer Care (Engl) 2017; 26: 5
  PubMedSearch in Google Scholar
• 139 Böttcher HM, Steimann M, Koch U, Bergelt C. Return to work – experiences and expectations of cancer patients during inpatient rehabilitation. Rehabilitation 2012; 51: 31-38
  Thieme ConnectPubMedSearch in Google Scholar
• 140 Broemer L, Esser P, Koranyi S, Friedrich M, Leuteritz K, Wiegand S, Dietz A, Boehm A, Pabst F, Strauß BM, Guntinas-Lichius O, Mehnert A. Machbarkeit einer Gruppenintervention zur Förderung der Arbeitsfähigkeit für Patienten mit Kopf-Hals-Tumoren. Laryngorhinootol 2019; 98: 175-182
  Thieme ConnectPubMedSearch in Google Scholar