Analiza kliničkih manifestacija i prognostičkih faktora timoma

Abstract

Uvod. Timomi su retke bolesti, ali najčešći tumori medijastinuma. Terapijski vodiči su zasnovani na rezultatima analiza retrospektivnih studija. Materijal i metode. Ovom retrospektivnom studijom analizirano je 62 bolesnika sa patohistološki verifikovanim timomom u Klinici za plućne bolesti Kliničkog centra Srbije u Beogradu, u periodu od 1993. do kraja 2013. Popunjavani su upitnici koji su podrazumevali podatke iz istorije bolesti, fizički pregled bolesnika, radiografije i/ili kompjuterizovane tomografije grudnog koša, operativne liste i/ili patohistološke nalaze biopsija. Analizirani su klinička slika, terapijski aspekti, preživljavanje i pojava relapsa bolesti. Timomi su klasifikovani prema patohistološkoj klasifikaciji Svetske zdravstvene organizacije i stažirani prema Masaoka-Koga sistemu. Dobijeni rezultati su kodirani, uneti u bazu podataka i analizirana je statistička povezanost pojedinih varijabli: demografskih, kliničkih, radiografskih karakteristika timoma, primenjenih terapijskih režima i njihov uticaj na dužinu preživljavanja bolesnika, tj utvrđivanje faktora koji utiču na pojavu relapse bolesti, kao prognostičkih faktora. Cilj. Definisati osnovne kliničke karakteristike obolelih od timoma, terapijske aspekte, preživljavanje i pojavu relapsa bolesti je bio cilj studije, kao i sagledavanje prisustva mutacija u genima kod timoma, radi utvrđivanja njihovog mogućeg uticaja na patogenezu timoma i prediktivnog značaja u preživljavanju, sa krajnjom idejom implementiranja target terapijskih opcija u praksi vezanih za genetiku timoma. Rezultati. Više je bilo obolelih žena (54,8%). Najveći broj pacijenata je bio u sedmoj deceniji života (32,3%). Skoro trećina pacijenata je bila asimptomatska (29%), a ostali su imali bar jedan simptom, najčešće je konstatovan kašalj. Najčešći paraneoplastički sindrom je miastenija gravis (12.9%). Najčešće je konstatovano prisustvo solitarne promene u grudnom košu (61.3%), tumora većeg od 5 cm (52.5%), neinvazivnih timoma (52.5%). Većina bolesnika je bila u I stadijumu bolesti (40%), a najčešći terapijski pristup operacija (88.7%). Statistički značajna razlika u preživljavanju konstatovana je u žena, pacijenata koji su imali solitarni tumor, neinvazivni timom, I stadijum bolesti i bolesnici kojima je sprovedena operacija. Dimenzija tumora je bila blizu granice konvencionalnog nivoa značajnosti. Smrtnih ishoda je bilo više u grupi pacijenata koji nisu imali mutacije u genima, izuzev kod pacijenata koji su imali mutaciju u TP53 genu. Aritmetička sredina (A.S.) preživljavanja je bila veća u grupi pacijenata bez mutacije u 4 gena (EGFR, KRAS, ATM, ERBB4), a u grupi sa prisutnom mutacijom takođe u 4 gena (MET, TP53, SMAD4, APC). A.S. preživljavanja je bila podjednaka kod pacijenata kod kojih je prisutna mutacija kao i kod onih kod kojih nije postojala mutacija u ALK genu...

Thymoma is the most common mediastinal tumor. The treatment procedures are based on the results from the research of retrospective studies because they are not frequent tumors. Methods. This study was performed in the Clinic for Pulmonology, Clinical Centre of Serbia, Belgrade from January 1993 to December 2013. We analyzed 62 patients of pathohistologically proven thymoma. The results were obtaind from medical history, physical exam, chest X-ray and/or computed tomography, and an operational finding or a report of a diagnostic procedure. The World Health Organization classifies thymoma on the basis of pathohistological findings. Thymoma are staged according to the Masaoka-Koga staging system. Aim. The objective of this work was to define common clinical features, therapeutic aspects, survival and recurrence free survival, as well as consideration of the presence of mutations in genes in patients with thymoma, for the purpose of determining their possible impact on the pathogenesis of thymoma and predictive significance in survival, with the final idea of implementing the target therapeutic option in practice related to the genetics team. Results. There were more female (54,8%) patients. Patients were mostly in the seventh decade of life. One third (29%) of the patients were asymptomatic. Cough was the dominant symptom. Myasthenia gravis was the most common paraneoplastic syndrome (12.9%). Solitary tumour was the most common in our patients (61.3%), as well as the tumours larger than 5 cm (52.5%), and noninvasive thymomas (52.5%). The majority of patients (40%) were in the stage I of the disease. The operative approach has been conducted in most of the patients (88.7%). A statistically significant difference in survival was in women, patients with solitary tumor, non-invasive thymomas, patients in the stage I of the disease, and those who were operated. The dimension of the tumor mass is approaching the conventional level of significance. Mortality was higher in the group of patients who did not have mutations in the genes, except in patients who have a mutation in the TP53 gene. Arithmetic mean (AM) of survival was higher in the patients without the mutation in the 4 genes (EGFR, KRAS, ATM, ERBB4), as well as in the group with the mutation in 4 genes (MET, TP53, SMAD4, APC). A survival rate was comparable in patients with the gene mutation as well as those in which there was no mutation in the ALK gene. A statistically significant difference between two groups in survival was found in patients with mutations in SMAD4 gene...