Preoperativna primjena imunoterapije u liječenju karcinoma pluća

master's thesis

• Title (english): Preoperative application of immunotherapy in the treatment of lung cancer
• Author: Marela Grgurić
• Mentor: Marko Jakopović (mentor)
• Committee member: Miroslav Samaržija (predsjednik povjerenstva)
• Committee member: Mateja Janković Makek (član povjerenstva)
• Committee member: Marko Jakopović (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2022-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract

Karcinom pluća predstavlja velik javnozdravstveni problem. Vodeći je uzrok smrti među karcinomima u oba spola, a kasno dijagnosticiranje predstavlja velik problem. Karcinom pluća u početku ne daje simptome i to je razlog njegovog otkrivanja u poodmaklim stadijima bolesti. Kemoterapija i radioterapija, kao dosadašnje metode, relativno slabo djeluju za izlječenje ili produljenje života pacijenta. Otkriće i uvođenje imunoterapije u liječenje karcinoma pluća bilo je revolucionarni napredak prema pretvaranju karcinoma pluća u kroničnu bolest. Tumor ima sposobnost izbjegavanja nadzora imunološkog sustava te time mogućnost rasta i metastaziranja. Imunoterapija se zasniva na poticanju protutumorskih mehanizama te kočenju rasta tumora. Principi imunoterapije temelje se na blokadi kontrolnih točaka, adoptivnoj staničnoj terapiji te imunoterapiji pomoću cjepiva. Od nabrojanih metoda, blokatori kontrolnih točaka pokazuju najbolju uspješnost u liječenju karcinoma pluća te se bolesnicima sa udjelom markera PD-L1 većim od 50% daju kao prva linija liječenja. S druge strane, operabilnim bolesnicima, stadij I-IIIA, do sada se u praksi neoadjuvatno primjenjivala kemoterapija ili zračenje sa relativno slabim uspjehom. Studije koje su u tijeku pokazuju kako neoadjuvantna primjena imunoterapije temeljena na blokatorima kontrolnih točaka može biti korisna kao predoperativna metoda za smanjenje tumorske mase ili presadnica tumora u limfim čvorovima. Neoadjuvantnom primjenom imunoterapije, pojedinačno ili u kombinacji sa kemoterapijom, preliminarni rezultati pokazuju ohrabrujuće promjene u vidu smanjenja tumora i metastaza koji bi mogli prije neoperabilne ili suspektno operabilne pacijente podvrguti operaciji. S druge strane, imunoterapija ima mnogo blaže simptome nego kemoterapija te manje iscrpljuje organizam pa bi samim time postoperativni oporavak bio brži i kraći. Osim usavršavanja imunoterapije kao lijeka, predoperativna primjena otvara nove mogućnosti za izlječenje i produljenje života pacijentima koji dosadašnjim metodama liječenja ne bi mogli biti operirani ili kod kojih bi oporavak bio duži i kompleksniji. Studije koje su u tijeku pokazuju pozitivne rezultate. Sumirano, neoadjuvantna primjena imunoterapije otvara nova poglavlja u liječenju karcinoma pluća te preostaje puno prostora za usavršavanje metoda i primjene.

Abstract (english)

Lung cancer is a major public health problem. It is the leading cause of death among cancers in both sexes, and late diagnosis is a major problem. Lung cancer does not show symptoms at first and that is the reason for its detection in advanced stages of the disease. Chemotherapy and radiotherapy, as current methods, have relatively little effect in curing or prolonging a patient's life. The discovery and introduction of immunotherapy in the treatment of lung cancer was a revolutionary advance towards the transformation of lung cancer into a chronic disease. The tumor has the ability to avoid the control of the immune system and thus the ability to grow and metastasize. Immunotherapy is based on stimulating antitumor mechanisms and inhibiting tumor growth. The principles of immunotherapy are based on checkpoint blockade, adoptive cell therapy, and vaccine immunotherapy. Of the listed methods, checkpoint blockers show the best performance in the treatment of lung cancer and are given as the first-line treatment to patients with a PD-L1 marker greater than 50%. On the other hand, in operable patients, stage I-IIIA, chemotherapy or radiation has so far been inadequately administered in practice with relatively poor success. Ongoing studies show that neoadjuvant immunotherapy based on checkpoint blockers may be useful as a preoperative method to reduce tumor mass or tumor transplants in lymph nodes. With neoadjuvant immunotherapy alone or in combination with chemotherapy, preliminary results show encouraging changes in the reduction of tumors and metastases that could undergo previously inoperable or suspiciously operable patients. On the other hand, immunotherapy has much milder symptoms than chemotherapy and is less debilitating, so postoperative recovery is faster and shorter. In addition to improving immunotherapy as a medicine, preoperative application opens up new possibilities for healing and prolonging the life of patients who could not be operated on with previous treatment methods or whose recovery would be longer and more complex. Ongoing studies show positive results. In summary, the neoadjuvant application of immunotherapy opens new chapters in the treatment of lung cancer and there is a lot of room for improvement of methods and applications.

• Keywords: karcinom pluća; neoadjuvantna imunoterapija; inhibitori kontrolnih točaka
• Keywords (english): lung cancer; neoadjuvant immunotherapy; checkpoint inhibitor
• Language: croatian
• URN:NBN: urn:nbn:hr:105:985724
• 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: 2023-01-09 09:39:07