<p>Karcinomi pluća su najčešći uzrok oboljevanja i umiranja od malignih tumora u Svetu. Neodjuvantna terapija kod bolesnika sa lokalno uznapredovalim (IIIA-IIIB) karcinomom pluća i zahvaćenim N2 limfnim čvorovima jedan je od modusa multimodalnog lečenja bolesnika sa nemikrocelularnim karcinomima pluća (NSCLC) u cilju poboljšanja ishoda njihovog lečenja. Ovakav pristup podrazumeva prevođenje bolesnika iz višeg u niži stadijum bolesti - „downstaging”. Do danas nije utvrđena povezanost između pojedinih obrazaca tumorskog odgovora i vrste terapije. S obzirom na značaj kompletnog patološkog odgovora i tumorske regresije u prognozi ishoda lečenja, iznalaženje ove povezanosti je od značaja za dizajniranje budućih neoadjuvantnih trajala. Prilikom utvrđivnja histološke slike tumorske regresije veoma je važno i merenje areje rezidualnog tumora (ART). Kako je veličina tumora jedan od prognostičkih faktora za bolesnike sa NSCLC koji nisu primali neoadjuvantnu terapiju tako je i merenje ART, za razliku od makroskopske veličine tumora, jedan od prognostičkih faktora za bolesnike sa NSCLC koji su primali neoadjuvantnu terapiju. Krajnji cilj neoadjuvantne terapije trebalo bi da bude resektabilnost i „downstaging” koji bi mogao da obezbedi u specifičnim kliničkim situacijama i sveukupni onkološki benefit. Osnovni ciljevi ove doktorske disertacije su bili: da se objektivizira procena veličine ART u tumorskom tkivu pluća i limfnih čvorova; da se proceni povezanost površine ART sa veličinom tumora na postoperativnom hirurškom materijalu posle neoadjuvantne terapije; da se analizira i proceni povezanost histomorfoloških parametara kod tumorske regresije indukovane neoadjuvantnom terapijom i spontane tumorske regresije u tumorima pluća i limfnih čvorova na postoperativnom hirurškom materijalu i u zavisnosti od histološkog tipa karcinoma; da se proceni povezanost kliničkog odgovora na neoadjuvantnu terapiju prema kriterijumima Svetske Zdravstvene Organizacije i histoloških parametara u tumorima pluća i limfnim čvorovima na postoperativnom hirurškom materijalu nakon neoadjuvantne terapije; da se proceni povezanost patološkog ypTN sa kliničkim ycTN stadijumom bolesti i stepena tumorske regresije indukovane neoadjuvantnom terapijom i patološkog ypTN i da se proceni povezanosti između kliničke i patološke zahvaćenosti N2 limfnih čvorova posle neoadjuvantne terapije. Merenje ukupne veličine očuvanih ART je najznačajniji objektivni parametar u proceni stepena tumorske regresije. Veličina rezidualnog tumora nije u korelaciji sa veličinom tumora posle neoadjuvantne terapije. Postoji signifikantna razlika u patohistološkoj slici tumorske regresije indukovane neoadjuvantnom terapijom i spontane tumorske regresije. Ne postoji signifikantna razlika između histološkog tipa tumora i histološke slike tumorske regresije. Ne postoji signifikantna povezanost između kliničkog odgovora i stepena tumorske regresije nakon neoadjuvantne terapije. Ne postoji korelacija između kliničkog i patološkog stadijuma bolesti posle neoadjuvantne terapije. Ne postoji korelacija između stepena tumorske regresije indukovane neoadjuvantnom terapijom i ypTN stadijuma bolesti. Ne postoji korelacija između kliničke i patološke zahvaćenosti N2 limfnih čvorova posle neoadjuvantne terapije. Stepen regresije tumora i merenje ART posle neoadjuvantne terapije određen histopatološkom analizom reseciranog tumora je najobjektivniji kriterijum za procenu hemioterapijskog odgovora i predviđanja ishoda lečenja pacijenata.</p> / <p>Lung cancers are the most common cause of morbidity and mortality from malignant tumors in the World. The neodjuvant therapy in patients with locally advanced (IIIA-IIIB) lung cancer and affected N2 lymph nodes is one of the modes of multimodal treatment of patients with non-small cell lung cancer (NSCLC) in order to improve the outcome of their treatment. This involves converting patients from a higher to a lower stage of the disease - "downstaging". There has been no significant connection between some forms of tumor response and types of therapy. Given the importance of complete pathological responses and tumor regression in the prediction of treatment outcomes, finding this relationship is of importance for the design of future neoadjuvant trails. In determining the histological tumor regression is very important measurement of area of residual tumor (ART). As the size of the tumor is one of the prognostic factors in patients with NSCLC who did not receive neoadjuvant therapy so the measurement of ART, as opposed to the macroscopic size of the tumor, one of the prognostic factors in patients with NSCLC, who had received neoadjuvant therapy. The ultimate goal of neoadjuvant therapy should be resectability and "downstaging" that could provide overall oncology benefit in specific clinical situations. The main objectives of this thesis were: to objectively estimate the size of ART in tumor tissue of lung and lymph nodes; to estimate the relation between the surface of ART with the size of the tumor on postoperative surgical material after neoadjuvant therapy; to analyze and estimate the relation between histomorphological parameters in tumor regression induced by neoadjuvant therapy and spontaneous tumor regression in tumors of the lung and lymph nodes in the postoperative surgical material and depending on the histological type of cancer; to estimate the relation between clinical response to neoadjuvant therapy according to criteria of the World Health Organization and histological parameters in lung tumors and lymph nodes in the postoperative surgical material after neoadjuvant therapy; to estimate the correlation of the pathological ypTN with clinical ycTN stage of the disease and the degree of tumor regression induced by neoadjuvant therapy and pathological ypTN and estimation of the relation between clinical and pathological involvement of N2 lymph nodes after neoadjuvant therapy. Measurement of the total size of the preserved ART is the most important objective parameter in the assessment of the grade of tumor regression. Size of residual tumor did not correlate with the size of the tumor after neoadjuvant therapy. There was a significant difference in the histological picture of tumor regression induced by neoadjuvant therapy and spontaneous tumor regression. There was no significant difference between the histologic type of tumor and histological tumor regression. There is no significant correlation between clinical response and the grade of tumor regression after neoadjuvant therapy. There is no correlation between clinical and pathological staging of the disease after neoadjuvant therapy. There is no correlation between the grade of tumor regression induced by neoadjuvant therapy and ypTN stage of the disease. There is no correlation between the clinical and the pathological involvement of the N2 lymph nodes to neoadjuvant therapy. The grade of tumor regression and measurement ART after neoadjuvant therapy determined by histopathological analysis of the resected tumor is the most objective criterion for evaluation of chemotherapeutic response and prediction of treatment outcome in patients.</p>
| Identifer | oai:union.ndltd.org:uns.ac.rs/oai:CRISUNS:(BISIS)101318 |
| Date | 14 September 2016 |
| Creators | Samardžija Golub |
| Contributors | Eri Živka, Stanić Jelena, Tadić Latinović Ljiljana, Živojinov Mirjana, Nikin Zoran, Sečen Nevena, Koledin Miloš |
| Publisher | Univerzitet u Novom Sadu, Medicinski fakultet u Novom Sadu, University of Novi Sad, Faculty of Medicine at Novi Sad |
| Source Sets | University of Novi Sad |
| Language | Serbian |
| Detected Language | English |
| Type | PhD thesis |
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