Prognostički značaj tumorske regresije i receptora za epidermalni faktor rasta u bolesnika sa uznapredovalim skvamocelularnim karcinomom jednjaka lečenih neoadjuvantnom hemio-radioterapijom
Prognostic significance of tumor regression grade and epidermal growth factor receptor in locally advanced squamous cell esophageal cancer treated with neoadjuvant chemoradiation
Докторанд
Arsenijević, Tatjana J.Ментор
Radošević-Jelić, LjiljanaЧланови комисије
Peško, PredragMicev, Marjan M.
Nikitović, Marina
Метаподаци
Приказ свих података о дисертацијиСажетак
Rezultati brojnih studija ukazali su na to da bolesnici sa skvamocelularnim
karcinomom jednjaka kod kojih je hemio-radioterapija dovela do kompletnog
histološkog odgovora imaju bolje preživljavanje. Međutim, svega 20-30%
bolesnika ostvari kompletnu remisiju na račun visoke toksičnosti. Za sada, nema
sigurnih markera predikcije odgovora na terapiju i prognoze preživljavanja ovih
bolesnika.
Cilj našeg istraživanja je bio utvrđivanje nivoa ekspresije EGF receptora u
preterapijskom histološkom uzorku karcinoma jednjaka, evaluacija kliničke i
histopatološke regresije (TRG) nakon neoadjuvantne hemio-radioterapije,
korelacija kliničke i histopatološke regresije sa prezivljavanjem i vremenom do
progresije kao i korelacija niova ekspresije EGFR sa odgovorom na hemioradioterapiju,
preživljavanjem i vremenom do progresije. Posebno je analizirana
stopa resektabilnosti, lokalne kontrole i toksičnost tretmana.
Studija je dizajnirana kao prospektivna, multicentrična, nerandomizovana i
obuhvatila je j...ednu grupu od 63 bolesnika sa histopatološki dokazanim lokalno
uznapredovalim skvamocelularnim karcinomom jednjaka. Ekspresija EGFR
markera je ispitivana imunohistohemijskim bojenjem u preterapijskom
biospijskom uzorku tumora. Svim bolesnicima je aplikovana konkomitantna
hemio-radioterapija. Bolesnici prevedeni u operabilni stadijum su
ezofagektomisani. Histopatološka evaluacija resekovanog uzorka obuhvatala je
proširenost tumora (ypTNM), rezidualni status i tumorski regresioni gradus (TRG).
Rezultati navedene studije pokazuju da skvamocelularni karcinom jednjaka
ima visok nivo ekspresije EGFR. Stopa kliničkog odgovora nakon hemioradioterapije
iznosila je oko 50%, a resektabilnosti 37%. Kompletan patohistološki
odgovor (TRG 1) iznosio je oko 26%. Eskpresija EGFR nije korelisala sa odgovorom
na hemio-radioterapiju. Dodavanje hirurgije poboljšava lokalnu kontrolu bolesti,
ukupno preživljavanje i vreme do progresije, ali ne utiče na udaljenu diseminaciju.
Uočili smo statistički značajano češću pojava relapsa u grupi EGFR pozitivnih
bolesnika, ali ni EGRF ni tumorski regresini gradus nisu korelisali sa ukupnim
preživljavanjem kao ni sa vremenom do progresije. Toksičnost tretmana je bila
značajna
The results of various studies imply better survival in patients with
squamous cell esophageal who achieve complete patohistological response to
chemoradiation. However, only 20-30% of patients will reach complete remission
on behalf of great toxicity. Up to now, there are no distinctive predictive and
prognostic markers that would suggest better response to treatment and survival
of these patients.
The aim of our study was to determine EGFR expression in pretherapy
esophageal cancer biopsy specimen, to evaluate clinical response and
patohistological regression grade (TRG) to neoadjuvant chemoradiation,
correlation of clinical and patohistological regression to survival and time to
progression, as well as correlation of EGFR expression to response to
chemoradiation, survival and time to progression. Resectability rate, local control
and treatment toxicity were analyzed also.
The study was designed as prospective, multicentric and nonrandomized.
Sixty three patients with histologically ...proven locally advanced squamous cell
esophageal cancer were enrolled. EGFR expression was evaluated by
immunohistochemical staining in a pretherapy tumor biopsy specimen. All
patients received concomitant chemoradiotherapy. Patients converted to operable
stage received surgery. Histological evaluation of resected specimen included
tumor expansion, (ypTNM), residual stage and tumor regression grade (TRG).
The results of this study showed that squamous cell esophageal cancer had
high EGFR expression. Clinical response rate was 50%, and resectability rate was
37%. Complete patohistologic response to chemoradiotherapy (TRG 1) was 26%.
EGFR expression did not correlate with response to chemoradiation. Addition of
surgery improved local control, overall survival and time to progression, but had
no impact on distant failure. We noted signifficantly higher relaps rate in EGFR
positive group of patients, but neither EGRF nor tumor regression grade correlated
with overall survival and time to progression. Treatment toxicity was considerable.