Uloga imunoterapije u liječenju bolesnika s metastatskim rakom bubrega

master's thesis

• Title (english): The role of immunotherapy in the treatment of patients with metastatic kidney cancer
• Author: David Zovko
• Mentor: Marija Gamulin (mentor)
• Committee member: Fedor Šantek (predsjednik povjerenstva)
• Committee member: Jasmina Marić Brozić (član povjerenstva)
• Committee member: Marija Gamulin (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Clinical Oncology); Zagreb
• Defense date and country: 2022-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Oncology

Abstract

Karcinom bubrega ubraja se među deset najčešćih zloćudnih novotvorina. Bolest može biti lokalna ili metastatska. Lokalno ograničena bolest ima znatno bolju prognozu od metastatske. Razvojem radioloških pretraga dijagnoza se sve češće postavlja u fazi lokalne bolesti. Najčešći histološki tip raka bubrega je svjetlostanični, drugi najčešći su papilarni i kromofobni. Stadij bolesti se određuje prema TNM-klasifikaciji. Prije početka liječenja metastatske bolesti treba odrediti stupanj rizika za bolesnika, koriste se MSKCC i IMDC modeli za tu svrhu. Osnovne metode liječenja metastatske bolesti su: kirurško liječenje, sustavna terapija i radioterapija. Od kirurških zahvata koriste se: citoreduktivna nefrektomija, limfadenektomija i metastazektomija. Liječenje sustavnom terapijom prije nije davalo rezultata zato što je rak bubrega kemorezistentan tumor. Razvojem novih lijekova nastaju bolje terapijske opcije. Skupine lijekova koje se danas koriste u sustavnoj terapiji uključuju: inhibitore kontrolnih točaka (imunoterapija), tirozin kinazne inhibitore, mTOR inhibitore i monoklonalna VEGF protutijela. Najbolju terapijsku opciju predstavljaju inhibitori kontrolnih točaka te tirozin kinazni inhibitori. Suvremene smjernice za liječenje prve linije metatstatskog svijetlostaničnog raka bubrega savjetuju primjenu dualne imunoterapije ili kombinirane imunoterapije s tirozin kinaznim inhibitorom. Česte su nuspojave kod primjene ovih lijekova, ali se nuspojave često smatraju biomarkerima odgovora na terapiju. Radioterapija ima primarno ulogu u palijativnom liječenju metastaza. Zahvaljujući primjeni imunoterapije najčešće u prvoj, rjeđe u drugoj liniji liječenja bolesnika s metastatskim rakom bubrega može se potpuno izliječiti oko 15% bolesnika. Liječenje metastatskog karcinoma bubrega ostaje i dalje izuzetno zahtjevno. Kod liječenja je potrebna redovita kontrola bolesnika uz multidisciplinarni pristup.

Abstract (english)

Kidney cancer is one of the ten most common malignant neoplasms. The disease can be local or metastatic. Locally limited disease has a significantly better prognosis than the metastatic one. With the development of radiological tests, the diagnosis is more often made in the local disease stage. The most common histological type of renal cell carcinoma is clear cell (ccRCC), and the second most common are papillary and chromophobe. The stage of the disease is determined according to the TNM classification. Before starting the treatment of metastatic disease, the risk level for the patient should be identified, and MSKCC and IMDC models are used for this purpose. Basic treatment methods for metastatic disease are: surgical treatment, systemic therapy and radiotherapy. The following surgical procedures are used: cytoreductive ephrectomy, lymphadenectomy and metastasectomy. Treatment with systemic therapy did not provide results before because kidney cancer is a chemo-resistant tumour. By developing new drugs, better treatment options were created. Drug groups used in systemic therapy nowadays include: checkpoint inhibitors (immunotherapy), tyrosine kinase inhibitors, mTOR inhibitors and monoclonal VEGF antibodies. The best therapeutic options are checkpoint inhibitors and tyrosine kinase inhibitors. Current treatment guidelines for first-line treatment of metastatic clear cell kidney cancer propose using dual immunotherapy or combined immunotherapy with tyrosine kinase inhibitor. Side effects are common when using these drugs, but they are often considered biomarkers of therapeutic response. Radiotherapy has a role primarily in palliative treatment of metastases. By implementing immunotherapy most commonly in the first, and less often in second line of treatment of patients with metastatic kidney cancer, approximately 15% of patients can be fully cured. Treatment of metastatic kidney cancer remains extremely demanding. Treatment requires regular monitoring of the patient and a multidisciplinary approach.

• Keywords: rak bubrega; metastatska bolest; imunoterapija; inhibitori tirozin kinaza
• Keywords (english): kidney cancer; metastatic disease; immunotherapy; tyrosine kinase inhibitors
• Language: croatian
• URN:NBN: urn:nbn:hr:105:633376
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-03-23 09:47:59