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Head and neck oncology

Head and neck squamous cell carcinoma (HNSCC) constitutes 90% of all head and neck cancers. It is the fifth most common type of cancer in men with approximately 780,000 new cases worldwide every year and is associated with high mortality rates as about one half of all individuals diagnosed with HNSCC will die within five years.













1) prognostic modelling

Prognostic models are used to predict survival of an individual patient. This prediction is very useful in the management of patients. The TNM (tumor size, regional and distant metastasis) grading system has been the mainstay of cancer outcome prediction for many years. This TNM system consists up to 60 categories. Variables such as age, sex, race, histologic type and grade also appeared to be important for prognosis. Combining all these variables results in thousands combinations of possibilities. Consequently, even in large cohorts of patients, many combinations of these characteristics occur only in very few patients. This makes prediction of survival in a new patient with the same specific combination of characteristics very difficult. This is one of the reasons that the TNM grading system is not very useful for prediction of outcome in an individual cancer patient at initial presentation.
To solve this problem of rare combinations, we use a new concept, which is based on the assumption that when each of these variables has an independent prognostic value. Prognosis may be composed on basis of the relative weight of each of these variables.  In such a model, it is not necessary to have previous experience with exactly the same patient, but one can rely on information supplied by all previous patients in the data-bank.
Based on some very high-quality patient databases (inter)national, prognostic models are being developed. Current focus is to improve existing models and to develop dynamic models. In addition to that, information from parallel research in molecular biology is added in order to establish further improvement. The resulting overwhelming amount of data is studied with traditional biostatistics, fuzzy logics, data-mining, data-fusion and bio-informatics.

2) Psychosocial and palliative care innovational research

The development of a patient owned chart (Logbook) was followed by the construction of an instrument to accelerate psychosocial screening and referral.
Furthermore, a controlled trial during the postoperative period at home was conducted. The purpose of this trial was to measure the  impact on quality of life with the use of a telemedicin system.

In the summer of 2005 an Expert Center of Palliative Care for Head and Neck Cancer patients became operational in our department. This multidisciplinairy palliative team consults mainly during the ambulatory stage. The objectives of this expert center are good symptom control, consultation toward other caregivers, targeted information, and structural support of patient and family, and research.

Psycho social factors and their association with survival in head and neck cancer is subject of an ongoing study

3) Partial laryngeal surgery
Oncological, functional and QoL aspects of supracricoid laryngectomies for recurrent disease has been, and still is, the focus of our research. Currently we are expanding the indication for this kind of conservation surgery to primary cancers as well. Combined with endoscopic surgery (laser) for early laryngeal carcinoma, we hypothesize that we can further reduce the number of total laryngectomy in the years to come. Especially since we purchased the first flexible CO2 laser in the Netherlands: this equipment allows us to resect tumors not amenable for rigid endoscopic surgery. The research is performed in cooperation with the departments of radiotherapy and speech therapy.

4) DNA-array and TMA
Despite advances in aggressive and multidisciplinary treatment approaches, there has been no evidence over the past 20 years to suggest any significant improvement in the 5-year survival rate. As current treatment strategies rely on clinical, radiologic, and histopathologic parameters, our department takes special interest in the cellular and molecular processes leading to neoplastic transformation and progression of HNSCC in order to design novel therapeutic and more accurate diagnostic approaches.

A large collection of surgically removed HNSCCs and close collaboration with the departments of pathology and internal oncology enables the department to perform a variety of experiments on several molecular levels, including DNA, miRNA and protein, which hopefully leads to the identification of a set of molecular markers that might offer new treatment modalities for patients with HNSCC. 

As HNSCCs are very heterogeneous tumours it might be so that preoperative tissue biopsies are not truly representative for the actual tumor stage. Therefore an assessment will be made of the extend of molecular and genetic intratumoral heterogeneity in HNSCC to prevent misdiagnosis in the future.

Beside effective therapies and accurate diagnosis, patients with HNSCC need a prognosis to re-organize their lives and adapt to the new situation. Additionally, a prognosis allows them to balance the burden of treatment against the possible gain in life expectancy and quality of life. At the moment the department possesses a prognostic model that predicts the survival probability of a patient diagnosed with HNSCC. Since this model is based on a patient database with clinical variables, inclusion of other types of variables might improve it. As the collection of tissue specimens mentioned above originate from a subset of patients in the clinical database, it will be investigated whether addition of a or a set of molecular markers improves the performance of the existing model.

5) Optic
Preoperative imaging of tumors in the head and neck region has made great progress over the last decades. For the surgeon however, a major challenge remains in the translation of these images to the operation field. A critical aspect of oncologic surgery is to adequately discriminate between tumor and normal tissue and consequently determine the tumor-free margin which is essential for the prognosis of the patient. Nevertheless, in the operating room, the surgeon is confined to visual appearance and palpation of the tumor and lymph nodes. Introduction of real-time imaging technologies into the operating room has the potential of traversing the gap between radiology and surgery, resulting in real-time image-guided surgery.
A promising new technique for this application is optical imaging using near-infrared fluorescence (NIRF) light. Imaging of optical contrast can be performed using antibodies or ligands conjugated to an optically active reporter to target a recognized disease biomarker. These agents are injected preoperatively and are imaged during surgery. This study assesses the feasibility of optical imaging to detect head and neck tumors and cervical lymph node metastasis in various animal models.

To develop head and neck cancer models, human cancer cells are inoculated into the tongues of nude mice. Tumor growth is followed by bioluminescence imaging. For this purpose, DNA encoding for the luciferase protein has been implanted into the DNA of the tumor cells. After injection of luciferin, tumor cells can be made visible as a control and noninvasive follow-up of tumor growth. When tumors have grown, fluorescence agents are injected and optical imaging is performed. Fluorescence signal intensity is compared to a control group of nude mice without tumor. After surgical resection of the primary tumor and cervical lymph nodes, histological analysis is performed.

The preliminary results demonstrate the feasibility of detection of head and neck tumors and cervical lymph node metastases using optical imaging in animal models. In combination with adequate camera systems, various NIRF agents could be used for real-time image-guided surgery of head and neck tumors. In this way, the technique has potential to improve survival and postoperative functionality by complete surgical resection of head and neck cancer. Various applications of optical imaging will be investigated in this project within the following years.

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