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Projects / Programmes source: ARIS

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

Periods
Research activity

Code Science Field Subfield
3.04.00  Medical sciences  Oncology   

Code Science Field
B200  Biomedical sciences  Cytology, oncology, cancerology 

Code Science Field
3.02  Medical and Health Sciences  Clinical medicine 
Keywords
cancer of the head and neck, molecular markers, image-cytometric analysis, chemotherapy, radiotherapy, treatment related side effects, survival
Evaluation (rules)
source: COBISS
Researchers (15)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  00705  PhD Marija Auersperg  Oncology  Researcher  2009 - 2013  203 
2.  00702  PhD Marjan Budihna  Oncology  Researcher  2009 - 2013  125 
3.  16048  PhD Igor Fajdiga  Oncology  Researcher  2009 - 2013  113 
4.  10946  PhD Irena Hočevar Boltežar  Oncology  Researcher  2009 - 2013  511 
5.  17474  Vojislav Ikič    Technical associate  2009 - 2013 
6.  17475  Igor Kjunder    Technical associate  2009 - 2013 
7.  09762  PhD Hotimir Lešničar  Oncology  Researcher  2009 - 2013  125 
8.  20052  PhD Irena Oblak  Oncology  Researcher  2009 - 2013  301 
9.  14576  PhD Primož Strojan  Oncology  Head  2009 - 2013  805 
10.  02130  PhD Alojz Šmid  Oncology  Researcher  2009 - 2013  215 
11.  05316  PhD Erika Šoba-Podobnik  Oncology  Researcher  2009 - 2013  52 
12.  21748  PhD Vaneja Velenik  Oncology  Researcher  2009 - 2013  259 
13.  02132  PhD Miha Žargi  Oncology  Researcher  2009 - 2013  392 
14.  20478  Tatjana Železnik    Technical associate  2009 - 2013 
15.  02133  PhD Avgust Župevc  Oncology  Researcher  2009 - 2013  78 
Organisations (2)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0302  Institute of Oncology Ljubljana  Ljubljana  5055733000  15,493 
2.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  77,706 
Abstract
Background: Cancer of the head and neck is a heterogeneous disease; therefore, a never-ending search for the factors predicting the aggressiveness of the disease in each individual patient is imperative as well as self-evident. The same holds for the evaluation of the efficiency of new treatment regimes or new treatment combinations because of poor treatment results in the patients with unresectable squamous cell carcinoma of the head and neck or in the patients who are not eligible for surgery or decline surgical treatment. Research Objectives: In the first, preclinical phase, the authors will focus the researches on primary tumor tissues and regional metastases of the patients included in the clinical phase of the study: In these tissues, (1) the expression of certain tumor markers will be determined by immunohistochemistry and immunocytochemistry, (2) DNA content, structural characteristics and organization of nuclear chromatin will be established by image cytometry. The objectives of this analysis are to identify those biological characteristics of a tumor that are vital for assessing the tumor aggressiveness, and thereby also for predicting the effectiveness of the treatment regime under study. In the second, clinical phase of the research, the authors will evaluate the toxicity and efficiency of concomitant chemoradiotherapy by applying (1) mitomycin C and cisplatin in the treatment of the patients with unresectable tumors (phase II study), or (2) cisplatin and concurrent inhalation of carbogen in the treatment of patients with resectable tumors who refuse to be surgically treated or are physically not fit to undergo surgery that may require radical removal of the larynx (phase I-II study). By Doppler ultrasound examination of the neck vessels in the patients in the studied group, we will select those in whom an aggressive cancer therapy may increase the risk of cerebrovascular insult and indicate them a prophylactic therapy.
Significance for science
1. MOLECULAR MARKERS We determined the value of cysteine proteases and their inhibitors as prognostic markers in patients with SCCHN: with a high degree of reliability, stefin A was recognized as the most promising marker from this group. The importance of this finding is even more pronounced because in head and neck cancer there is no laboratory marker which could be used for prediction of treatment results or survival. In addition, immunohistochemical analysis of stefin A was identified as reliable and the most appropriate method for routine use (compared to biochemical analysis of cytosolic or serum samples). Stefin A proved to be a good marker for identification of patients with increased risk for disease recurrence in the neck, who are at present considered as intermediate-risk group (metastases in the neck nodes but without extracapsular tumor extension). Additional data on aggressiveness of malignant disease in individual patient, which also allow more personalized treatment, were obtained through research work on the prognostic role of cytometric features and CT perfusion parameters. 2. RADIOCHEMOTHERAPY We extended the knowledge on therapy options in SCCHN. With establishing the data base on all patients with SCC of the oral cavity, oro-, hypopharynx and larynx treated with curative RT durng 2007-2007 in Slovenia, an important source of information was created, which allowed a detailed analysis of treatment results of these cancers in the country. We found that treatment result depends on treatment modality, intensity of added chemotherapy and waiting time for RT. In preclinical studies on mechanisms of vinblastine action, important information for clinics was collected: effectiveness of RT/vinblastine combination is highest if tumors are irradiated at the beginning of prolonged infusion of the drug (most probably due to preferential binding to microtubules and the absence of radiobiologically relevant hypoxia). In cooperation with the Jožef Stefan Institute an analytical method for vinblastine measurements in tumor tissue (with liquid chromatography-high resolution mass spectroscopy) was developed, which allows its precise quantification in biological samples. 3. RARE TUMORS OF THE HEAD AND NECK Analysis of our treatment results and comparison to the literature data allowed us preparation of more selective guidelines for postoperative treatment of patients with melanoma metastases in the neck, for treatment of sinonasal inverted papilloma and neck metastases of SCCHN, and re-irradiation of SCCHN patients who have already been irradiated in the head and neck area. In all listed cases, a more precise determination of indications for RT and parameters of RT technique were made possible (size of irradiation volumes, daily and total RT dose). 4. EFFECTS OF ONCLOGICAL TREATMENT 4.1 QUALITY OF VOICE AFTER IRRADIATION OF LARYNGEAL CANCER (AND RELATED ETHIOLOGIC FACTORS Recognition of the relationships among gastroesophageal reflux (GER), vocal load and cancer development in this area pointed to pre-RT treatment of GER; the most exposed to GER are singers. Second finding is that better voice quality after RT can be achieved in case of smoking cessation and with an appropriate voice therapy. Pharyngocutaneous fistula as complications of salvage total laryngectomy, which is usually the only possible treatment of recurrent malignant disease in the larynx, can be successfully prevented/reduced with the use of flaps reconstruction from outside of irradiation field. 4.2 IMPACT OF DELAY IN INITIATING RADIOTHERAPY ON OUTCOME Inverse relationship between waiting time for RT and effectiveness of RT, which was convincingly confirmed on large sample of our own patients, is a direct evidence of a negative effect of shortage of RT capacities in population. This finding serves as an indisputable argument that speaks in favor of an urgent improvement of situation in countries facing problems in this segment of oncological treatment.
Significance for the country
1. MOLECULAR MARKERS Precondition for more individualized approach to patients is as detailed description of biological characteristics of the tumor in an individual patient as possible. Namely, it is of paramount importance to treat intensively enough patients with more aggressive forms of the disease (to avoid disease recurrences), while the others less intensively (to save them from excessive toxicity). With recognition of immunohistochemically determined stefin A as an indicator of increased risk for disease reappearance in group of patients with metastases in regional neck nodes but without extracapsular tumor extension, we will be able to identify patients from this group who need additional (or more intensive) treatment. Personalization of treatment is allowed also by the results of cytometric features and CT –perfusion analyses. 2. RADIOCHEMOTHERAPY With the establishment of data base on patients with SCCHN who were treated in Slovenia between 2004and 2007, the effectiveness of individual oncological treatment interventions on the level of the entire country was assessed for the first time. This data base, which is intended to be expanded in the following years with gradual involvement of new calendar years, will serve for current assessment of treatment efficacy of SCCHN patients in Slovenia and individual patients’ subgroups. At the same time, it allows evaluation of existing radio(chemo)therapy protocols, which represents additional step toward more individualized management of the patients. 3. RARE TUMORS OF THE HEAD AND NECK Analysis of treatment results and critical reviews of the literature are a starting point for preparation of more selective guidelines for treatment of rare cancers and clinical situations studied (melanoma, sinonasal inverted papilloma, SCCHN metastases in the neck, re-irradiation). 4. EFFECTS OF ONCOLOGICAL TREATMENT Detailed analysis of treatment side effects with voice evaluation in irradiated patients with laryngeal carcinoma provides basis for preparation of guidelines for introduction of prophylactic/supportive therapy and for thought about other (less toxic but comparably effective) treatment options. In our studies we determined some important factors contributing to development of toxicity (e.g. gastroesphageal reflux, GER), which probably play a role also in development of the disease itself, and identify subgroups with increased risk for the development of these toxicities or disease (smokers, singers). The finding of clearly negative impact of the delay in initiation of RT to treatment outcome and survival of our patients with SCCHN will serve as a platform for planning of systemic measures which should improve RT situation in the country. OTHER Results of activities of the program group related to a public awareness (handouts, booklets, campaign “Speak out about head and neck cancer”) contribute to changes of attitude and consciousness of civil society about the danger of this particular type of cancer and difficulties in its treatment. With the organization of meetings, professional (Otolaryngology day – organized annually) and scientific (Congress of Otolaryngologists of Slovenia, with international participation – organized every 4 years), the knowledge of professionals about the disease itself and potential treatment options is improving.
Most important scientific results Annual report 2009, 2010, 2011, 2012, final report, complete report on dLib.si
Most important socioeconomically and culturally relevant results Annual report 2009, 2010, 2011, 2012, final report, complete report on dLib.si
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