Keywords

Introduction

The concept of a Comprehensive Cancer Center was first develpoed in France French Comprehensive Cancer Centers (2021). As we practice it here in Germany it is rather similar to the concept that has been established in the USA National Comprehensive Cancer Network: NCCN (2021). Comprehensive Cancer Centers are expected to initiate and conduct early phase, innovative clinical trials and to actively participate in trials of the National Cancer Institute (NCI) of the USA and in turn receive funding from the NCI. They must show activities in outreach and education both for health-care professionals and the public and demonstrate expertise in laboratory, clinical, epidemiological, and health-care research National Comprehensive Cancer Network: NCCN (2021). This concept has been adapted by other countries including Germany. Here, with a different structure of health-care delivery, CCCs exhibit close similarities but also slight differences to the structure in the USA (Das Netzwerk der Onkologischen Spitzenzentren (2021); Deutsche Krebshilfe: Onkologische Spitzenzentren (2021)). Running a CCC is challenging at several levels that are outlined in this paper.

The core features of a CCC in Germany are shown in Fig. 1.

Fig. 1
figure 1

Core features of a CCC in Germany. Left—Strong and comprehensive research and clinical trial program. Center—Supraregional education and teaching in oncology and outreach program. Right—Established structure in the multidisciplinary management of cancer care in all aspects including psychooncology, nutritionists, patient self-help groups, and social work follows all current guidelines in oncology and has an established quality management system, certified by an established certification system

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Multidisciplinary Tumor Boards

The multidisciplinary tumor boards are at the heart of the clinical management of patients in a CCC. The boards meet regularly (at least weekly), and the participation of all specialties involved in the treatment of a certain tumor entity is mandatory. For example, for gastrointestinal (GI) cancer, the tumor board comprises visceral surgery, GI oncology, gastroenterology, pathology, radiology, radiation therapy, and nuclear medicine. The board discusses all patients newly diagnosed with a GI cancer, relapsed patients, patients with a change of strategy (e.g., secondary resection of liver metastases after chemotherapy), and patients having received procedures (e.g., TACE or SIRT). This means that patients are usually presented several times in the tumor board during their continuum of care. This is challenging particularly for cross-sectional specialties like pathology and radiology that have to attend multiple tumor boards, which is time-consuming both for preparing and attending and demanding for a specialty since the requirement for participating in a tumor board is consultant level. Qualification is important because decisions taken by the board should not be overturned by a single specialty unless for good reasons. Participation of the respective specialties as well as adherence to the criteria defined above and the tumor board decisions are regularly monitored. Unfortunately, there is no funding structure allowing to compensate for the additional time it takes to prepare and carry out the tumor boards.

IT Infrastructure

IT infrastructure of a CCC comprises various aspects: electronic patients’ records, a tumor board management system, a trial management system, and a cancer registry software ideally all interlinked in order to facilitate documentation and avoid repetitive entries into different databases.

This can be exemplified with a tumor board management system. Using an advanced and well-linked tumor board management system has several key advantages: data entry is only once and can be taken over by all documentation systems during the continuum of treatment of a given patient. With the introduction of mandatory fields in the documentation system, one can make sure that all the necessary information to take a sensible decision in the tumor board is actually available. This enables also better second-opinion decisions particularly when the treating physician is not able to present the patient’s case in person in the tumor board. Such a system can also list clinical trials running at the site the patient may be eligible for and should enable an on the spot, transparent documentation of the tumor board decision.

A clinical trial management system is also extremely useful when it is fully integrated into the hospital’s patient management system. First of all, it provides an easy overview on all trials running at the center and on all patients recruited into a specific trial. Furthermore, it can immediately indicate in an emergency that a certain patient participates in a clinical trial when they are seen at the hospital’s A&E department. Upon admission of a patient, the physicians can see whether the patient is on a trial, the kind of treatment the patients receive, learn the potential side effects of the study medication, get in touch with the study team, and choose an appropriate treatment if the patient’s condition has been judged as study treatment related. Ideally both the tumor management system and the clinical trial management system are also closely linked to the tumor documentation system. We developed our own system called CREDOS for Cancer Retrieval Evaluation and Documentation System that is linked to all other systems described above and fulfills all the statutory criteria for the official tumor documentation. It also enables the documentation of all items required for the certification of our CCC as an “Oncology Center” by the German Cancer Society. The major advantage of having a proprietary system is that it allows customization to the ever-changing needs in cancer documentation, for example, with the upcoming requirement of documenting data from NGS (next-generation sequencing) used for molecular characterization of a tumor and personalized treatment of patients. Having said all of that, setting up and maintaining such an IT infrastructure which goes beyond the standard setting of a university hospital requires resources that are not included in the regular funding schemes.

Structuring Patient Care

Ideally multidisciplinarity in a CCC is not only practiced at the level of the tumor boards, SOPs (standard operating procedures), and clinical trials but also at the level of direct patient care. This includes interdisciplinary management teams, for example, in an outpatient clinic for GI cancers that is run by a GI oncologist and a surgeon with an additional radiotherapist or other specialties (e.g., nuclear medicine) if need be. Here the patient gets a comprehensive assessment and treatment concept from all parties involved in the management of their disease, and all questions and issues can be addressed appropriately. This type of clinic is also very useful for patients seeking a second opinion on their case.

Clinical Trial Center

Since CCCs are in charge of both delivery of care and research, they are the ideal structures to run innovative high-level clinical trials, particularly investigator-initiated trials and phase I/phase II including first in human trials. To this end, they need well-structured clinical trial centers that accompany the whole process from writing the protocol up to negotiating contracts and initiating and monitoring multicenter trials. This does not only require trained study nurses and physicians, a quality management, and an education infrastructure, for example, for GCP courses, but also an appropriate IT infrastructure. The number of patients included into clinical trials in each tumor entity is monitored. In solid tumors, at least 10% of the patients seen at the center should be included into a clinical trial.

Research Infrastructure

Additional, but important, features of a CCC are access to a modern research infrastructure including genomics, proteomics, and bioinformatics. A CCC needs an established and well-maintained biobank. This comprises ideally not only paraffin embedded but also the fresh frozen normal and tumor tissue, liquid biobanks (e.g., for analysis of ctDNA, circulating tumor cells, or hematological tumors), a stool biobank (for microbiota analyses), and various other analytes including urine and ascites.

Well-annotated biobanks are a paramount prerequisite for personalizing tumor therapy and establishing novel prognostic and predictive biomarkers for various oncological treatments. They also feed into collaborative research centers, research training groups, and other basic and translational research units at a respective site.

Care Over and Above Medical Treatment

In recent years, it has become more and more evident that apart from excellent medical care, cancer patients also need structured help in many other areas to cope with their disease. This is particularly important with prolonged periods of treatment and consequently more side effects of the treatment and a higher burden for patients. Thus, psychooncology care is an important feature of a CCC and reaches from the cancer diagnosis to the time a patient has survived cancer but still suffers from treatment-related side effects or psychological constraints. In this context, also social work is important to avoid financial difficulties and support the well-being of the patient. Also, other aspects need to be taken into account in a CCC: physical exercise is an important measure to improve outcome of a particular treatment, accelerate rehabilitation, and improve quality of life during chemotherapy and also for secondary and tertiary prevention of cancer. Thus, structured programs for exercise therapy are another part of the comprehensive cancer care in a CCC. Last but not least, nutrition is also important in cancer care, and oncological nutritional counseling is another important component of a comprehensive cancer care package in a CCC. All these structures require less investment but appropriate and sustainable staffing to be successful thereby creating a challenge for the financial resources of a CCC.

Quality Management

Given all the requirements stated above, it is clear that a CCC needs a clearly defined quality management system. Regular quality circles aim at recognizing, discussing, and detecting problems and challenges as early as possible. These circles take place every 3 months. All parties involved in the tumor boards are invited to these circles. The circles are logged, and the decisions taken are important components for the further development of the center.

Regular mortality and morbidity (M&M) conferences are another, very important hallmark of the quality management. They also take place four times a year and review particular treatment histories and deaths. The M&M conferences aim at deriving concrete measures to improve the quality and safety of patient care at the center and to avoid potential mistakes in the future as much as possible.

Quality management also encompasses regular surveys of referring physicians and patients regarding satisfaction with the services provided by the center. The evaluation of these surveys is also the basis for the action plan of the Comprehensive Cancer Center Ulm (CCCU) (2021) since reducing cancer-related morbidity and mortality is the overarching goal of these centers.

Structuring the Clinical Work

A CCC shall define how it operates and has to define multidisciplinary standard operating procedures for all tumor entities treated but also for all supportive measures taken by the CCC. They shall be consented by all participating parties and must be updated regularly. In case of the CCCU, these are 53 SOPs covering different tumor entities and 39 SOPs for supportive treatment. This is a time-consuming and laborious task, since these guidelines are based on international and national guidelines, double-checked for subject-specific demands of all disciplines involved, and innovation must be covered in word and deed. All SOPs must also be consented by the cooperating partners, and their input shall be taken into account to ensure that the whole catchment area of the CCC follows the same SOPs.

Outreach Activities

A very important part of the activities of a CCC is outreach. The goal is to provide state-of-the-art care in oncology not only at the center itself but in the whole catchment area of the CCC. For this purpose, a CCC will set up a network of cooperating centers (in case of Germany either hospitals or private practices). Within this network, regular education and training activities as well as information on novel clinical trials the peripheral centers take place. These activities result in referring patients for inclusion or becoming recruiting centers themselves. There is not only education for physicians with seminars and lectures but also structured activities such as a master’s program in advanced oncology and joint postgraduate education with collaboration partners. Ideally, there are also structured training programs for oncology nurses. An important part of the outreach program is the interaction with patient self-help groups and educating patients and their relatives and learning their needs. For this purpose, the CCC organizes regular educational events together with patient self-help groups on various topics covering not only medical issues but also psychooncology and social support for cancer patients and their families.

Getting Funded

In contrast to the USA with a National Cancer Institute that provides funding for CCCs, there is no such structure in Germany. Thus, the CCCs receive only the regular funding for cancer documentation, but there is no overhead paid by the statutory health insurances or the federal and regional authorities to support the complex CCC structure outlined above. The German Cancer Aid, a charity dedicated to support research and treatment of cancer in all aspects, has launched a program funding CCCs when they fulfill certain criteria that are evaluated regularly by an international expert panel in audits. This provides funding for some aspects of a CCC but does not fully support the structure and is not an overarching structure providing enrollment into clinical trials. There is therefore a high level of commitment by all parties contributing to the CCC supporting the structure with staff as well as resources from their own departments as well as raising money from third parties.

Conclusion

In conclusion, running a comprehensive cancer center is a continuous process and development that is absolutely worthwhile to further improve treatment for cancer patients in all aspects. It takes time to completely implement all the components of a CCC. Working in multidisciplinary teams and combining clinical excellence with research is the philosophy of a CCC and broadens the clinical horizon. A major challenge in running a CCC is funding, but with commitment and enthusiasm, a CCC can achieve excellent results in a good multidisciplinary atmosphere promoting basic, translational, and clinical science. And with all of that, it helps our patients and their families.