Projects / Programmes source: ARRS

Cancer of the head and neck - analysis of biological characteristics and an attempt to improve treatment results

Research activity

Code Science Field Subfield
3.04.00  Medical sciences  Oncology   

Code Science Field
B000  Biomedical sciences   

Code Science Field
3.02  Medical and Health Sciences  Clinical medicine 
head and neck cancer; systemic therapy; radiotherapy; surgery; treatment; prognosis; human papillomavirus; side effects; gene polymorphism; electrochemotherapy; narrow-band imaging endoscopy; MR-perfusion; MR-diffusion; carcinoma of the oropharynx; cetuximab;
Evaluation (rules)
source: COBISS
Data for the last 5 years (citations for the last 10 years) on May 29, 2023; A3 for period 2017-2021
Data for ARRS tenders ( 04.04.2019 – Programme tender , archive )
Database Linked records Citations Pure citations Average pure citations
WoS  577  10,680  9,872  17.11 
Scopus  578  12,700  11,765  20.35 
Researchers (22)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  36160  PhD Aleksandar Aničin  Medical sciences  Researcher  2019 - 2023  120 
2.  18297  MSc Marta Dremelj  Medical sciences  Technician  2019 - 2023  36 
3.  16048  PhD Igor Fajdiga  Medical sciences    2019 - 2023  113 
4.  36605  PhD Aleš Grošelj  Medical sciences  Researcher  2019 - 2023  144 
5.  10946  PhD Irena Hočevar Boltežar  Medical sciences  Researcher  2019 - 2023  499 
6.  18300  MSc Katarina B. Karner  Medical sciences  Technician  2019 - 2023  36 
7.  51873  Urša Kešar  Medical sciences  Junior researcher  2020 - 2023  11 
8.  51868  Marko Kokalj  Medical sciences  Technician  2019 - 2023  13 
9.  16229  PhD Viljem Kovač  Medical sciences  Researcher  2019 - 2023  293 
10.  53564  Kristina Levpušček  Medical sciences  Junior researcher  2019 - 2022  14 
11.  38225  PhD Martina Nikšić Žakelj  Medical sciences  Junior researcher  2019  25 
12.  20052  PhD Irena Oblak  Medical sciences  Researcher  2019 - 2023  281 
13.  38481  Gaber Plavc  Medical sciences  Technician  2019 - 2023  29 
14.  21713  PhD Nada Rotovnik Kozjek  Medical sciences  Researcher  2019 - 2023  885 
15.  14576  PhD Primož Strojan  Medical sciences  Principal Researcher  2019 - 2023  789 
16.  36114  Robert Šifrer  Medical sciences  Researcher  2019 - 2023  114 
17.  33508  PhD Katarina Šurlan Popović  Medical sciences  Researcher  2019 - 2023  257 
18.  21748  PhD Vaneja Velenik  Medical sciences  Researcher  2019 - 2023  251 
19.  21698  MSc Ilija Vojvodić  Engineering sciences and technologies  Technician  2019 - 2023  10 
20.  02132  PhD Miha Žargi  Medical sciences    2019 - 2023  392 
21.  20478  Tatjana Železnik    Technician  2019 - 2023 
22.  21747  Barbara Žumer  Medical sciences  Technician  2019 - 2023  12 
Organisations (2)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0302  Institute of Oncology Ljubljana  Ljubljana  5055733000  14,547 
2.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  74,072 
The research program is designed in 3 work packages (WP), which together include 7 topics. All topics deal with current issues in the treatment of head and neck cancer (HNC). In the first WP, there are 4 topics dealing with new approaches to the treatment of H&N cancer. The ultimate goal of all is to improve patient selection for individual therapeutic programs either from the aspect of the type of treatment (s) or intensity of treatment. We will try to improve the selection of patients by: identifying genes and their polymorphisms that are crucial for the repair of DNA damage caused by cisplatin; with the help of the endoscopy with narrow-band imaging system, i.e. methods that are already being established in oncology; studying the pharmacodynamics and pharmacokinetics of bleomycin as the most commonly used chemotherapeutic in electrochemotherapy; by comparing quantitative magnetic resonance perfusion/diffusion parameters and tissue biomarkers of the early tumor response to treatment with chemoradiotherapy with cisplatin. The second WP is designed to study HPV (Human papillomavirus) – positive squamous-cell carcinomas of the oropharynx. They were found to respond significantly better to treatment with radiotherapy and some cytostatics. Therefore, the results of treatment of these tumors are significantly better than in other (HPV-negative) carcinomas of this region. In the context of this topic, a prospective clinical study is planned in which we will reduce the intensity of treatment and, consequently, its toxicity in selected patients with HPV-positive cancers, with the response of the tumors to the treatment and survival of the patients remaining unchanged. In the third WP, we will study the consequences of oncological treatment in two topics. The first topic combines the research in which we will use subjective and objective methods to evaluate disorders of the functions of the upper aerodigest tract (breathing, voice, swallowing) and associated gastroesophageal reflux disease and the effects on the quality of life. In another topic, we will try to find the causes of abnormally frequent and severe allergic reactions to cetuximab in Slovenian patients with H&N cancer, which was observed in our past clinical trials and does not match the experience of researchers from other countries and parts of the world.
Significance for science
WP 1 New approaches to the treatment Theme 1. Effect of genetic variability of DNA repair genes on the efficacy of chemadiadiotherapy with cisplatin in HNC The knowledge of genes and their polymorphisms that are important for the repair of DNA damage following irradiation and cisplatin exposure will enable us to select (based on the results obtained from tumor tissue analysis) among the patients, who are candidates for treatment with concurrent cisplatin-based chemoradiotherapy, only those who will respond to this treatment modality. Other patients will be treated with other therapeutic programs. Theme 2. Endoscopy with narrow-band imaging (NBI) This is a new endoscopic method that is only being established. With the planned research we will supplement/expand the knowledge in the areas, where the NBI is already in use (importance for achieving R0 surgical margin, the use of European Laryngological Society classification), and test the usefulness of NBI in the new areas and for other/new indications (effect on the risk for pharyngocutaneous fistula development after laryngectomy). Theme 3. Electrochemotherapy: a clinical-pharmacological approach to optimization of therapeutic concentration of bleomycin. The analysis of pharmacokinetics and pharmacodynamics of bleomycin that is the most commonly used chemotherapeutic drug in electrochemotherapy will enable the optimization of the therapeutic protocols in different age groups of patients. If the hypothesis (in the elderly patients, a lower dose of bleomycin is required to achieve a favorable therapeutic effect) will be confirmed, the toxicity of the treatment will be significantly reduced. Theme 4. Quantitative MRI perfusion and diffusion parameters and biospecimen-derived biomarkers in prediction of response to concurrent chemoradiotherapy of locoregionally advanced HPV-negative squamous cell carcinoma of the pharynx With the recognition of tissue biomarkers in bioptic tumor samples (taken prior to the treatment) that correlate with early changes in MRI perfusion and diffusion parameters, important for the response of the tumor to cisplatin-based chemoradiotherapy, we would be able (already in the treatment planning phase) to exclude those patients who will not respond and to direct these patients to other therapeutic programs. WP 2 Human papillomavirus (HPV) Theme 1. Treatment optimization of HPV-positive squamous cell carcinoma of the oropharynx (SCCOP) With decrease of treatment intensity in selected patients with HPV-positive SCCOP, with no change in the effectiveness of treatment, the toxicity of oncological therapy will be reduced, which will result in significant improvement of therapeutic ration. WP 3 Sequelae of oncological treatment Theme 1. Evaluation of the upper aerodigestive tract functions after oncological treatment The study of the mechanisms and the time dynamics of disorders of the various functions of the upper aerodigestive tract, including gastroesophageal reflux disease, and the knowledge of their impact on the quality of the patient's life will enable the elaboration of preventive measures and activities to reduce the incidence and severity of these conditions. Theme 2. Allergic reactions to cetuximab in Slovenian patients with HNC: the definition of causes With the planned study, we will try to clarify the causes of abnormally frequent severe infusion/allergic reactions at the first application of cetuximab, which was observed in Slovene patients with HNC.
Significance for the country
Research studies focused on individual approach to management of the head and neck cancer (HNC) patients (i.e. assessment of the impact of genetic variability of DNA repair genes on efficacy of chemoradiotherapy with cisplatin; predicting early tumor response to the treatment with tissue biomarkers and quantitative MRI diffusion and perfusion parameters; optimization of treatment of HPV-positive squamous cell carcinoma of the oropharynx) will enable more targeted, individual patient- or disease-adjusted treatment, which allows more effective patient selection for individual therapeutic programs. Namely, it is of paramount importance to treat with sufficient intensity and with appropriate modes of therapy patients with more aggressive forms of the disease (to avoid disease recurrences), while treating the rest less intensively (to save them from excessive toxicity). Studies in electrochemotherapy with bleomycin will also contribute to a better selection of patients in this type of treatment, as older patients should be efficiently treated with lower bleomycin doses than younger patients, due to age-related changes in the functioning of the organs. Of course, the reduced doses of bleomycin lower the toxicity of the treatment. The proposed research in the field of endoscopy with narrow-band imaging (NIB) means primarily the expansion of the existing diagnostic possibility in the field of HNC management in Slovenia. If the hypotheses are confirmed, the NIB will significantly contribute to the accuracy of the diagnosis (assessment of lesions on the vocal cords) and to reduction of the risk of disease recurrence (assessment of surgical edges) and of the development of certain complications of the treatment (pharyngocutaneous fistulae following laryngectomy), which all reduce the costs of the treatment in these patients. Prospective recording and detailed analysis of the effects of oncological treatment on breathing, swallowing, speech and quality of life provide a basis for preparation of guidelines for the introduction of preventive measures, early rehabilitation and appropriate supportive therapy, which will help patients to cope with the illness and treatment. Identification of the causes of frequent and severe allergic reactions to cetuximab in Slovenian patients with HNC, which are not identified in other countries and parts of the world (except for the countries of the Southeastern United States), will contribute to the recognition of Slovenia and its oncology profession. The extension and renewal of therapeutic and diagnostic offer with more focused (to distinct, i.e. targeted groups of patients) and complex protocols means a greater competitive ability of local oncological community (in relation to abroad). This is linked to demand for increase in the number of medical doctors nursing and other professional staff (due to more demanding diagnostics, treatment and control of adverse effects), upgrade of their educational profile, technological restructuring of activities (diagnostics and radiotherapy in particular) and introduction/wide accessibility to new technologies (MRI, CT, 3D radiotherapy). Activities of the program group members directed to public awareness (internet, lectures, assistance/collaboration with laic patients’ associations) will contribute to the changes in the attitude and consciousness of civil society about the danger of this particular cancer type and difficulties in its treatment, which will stimulate development of some social activities (e.g. volunteers, social work centers). Pedagogical activity of the program group members at undergraduate and postgraduate level (academic, specialist) will improve the knowledge of current and future professionals about the disease and potential treatment options. Result of all these efforts should be more cured patients and better quality of their life. Every new finding of indigenous researchers that belongs to either the field of tumor biology or clinically orien
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