Unit:
Τομέας ΚλινικοεργαστηριακόςLibrary of the School of Health Sciences
Author:
Karatrasoglou Eleni
Dissertation committee:
Χάιδω Σπηλιοπούλου, Καθηγήτρια, Ιατρική ΕΚΠΑ
Πηνελόπη Κορκολοπούλου, Καθηγήτρια, Ιατρική ΕΚΠΑ
Νικόλαος Καβαντζάς, Καθηγητής, Ιατρική ΕΚΠΑ
Σταμάτιος Θεοχάρης, Καθηγητής, Ιατρική ΕΚΠΑ
Αγγελική Σαέττα, Αναπληρώτρια Καθηγήτρια, Ιατρική ΕΚΠΑ
Αφροδίτη Νόννη, Αναπληρώτρια Καθηγήτρια, Ιατρική ΕΚΠΑ
Στρατηγούλα Σακελλαρίου, Επίκουρη Καθηγήτρια, Ιατρική ΕΚΠΑ
Original Title:
Μελέτη βιοδεικτών στο μη μικροκυτταρικό καρκίνο του πνεύμονα
Translated title:
Biomarker analysis of non-small cell lung cancer patients
Summary:
Lung cancer is the leading cause of cancer death worldwide. Many patients have metastatic disease at diagnosis and prognosis is dismal with 21% 5-year overall survival for all stages. Recently, promising therapies have emerged based on PD-1/PD-L1 immune checkpoint inhibitors which have been approved even as frontline treatment for patients with non-small cell lung cancer (NSCLC). We examined the association between PD-L1 expression and clinicopathological parameters as well as overall survival in 220 NSCLC patients. PD-L1 expression using 22C3 PharmDx DAKO monoclonal antibody (mAb) was defined as high when tumour proportion score (TPS) was ≥50%, low if TPS was 1-49% and absent when TPS was <1%. EGFR mutations were detected by COBAS, while KRAS and BRAF by Pyrosequencing. ROS1 and ALK rearrangements were estimated by immunohistochemistry with positive cases being confirmed by CISH and FISH respectively. Finally, ERCC1 and RRM1 expression was estimated by immunohistochemistry. Data analysis was performed using SPSS v24.0. PD-L1 expression was positively correlated with KRAS mutations. Anti-PD-1 therapy (pembrolizumab) prolonged patients overall survival compared to any other treatment strategy. Interestingly, when pembrolizumab combined with the presence of KRAS mutations showed a statistically significant difference (p<0.001) in overall survival compared to absence of KRAS mutations. Moreover, when ERCC1 expression combined with the platinum-based chemotherapy, showed that patients with no ERCC1 expression had a statistically significant survival benefit (p<0.001). In multivariate analysis, PD-L1 status, stage and anti-PD1 treatment were independent variables for overall survival. Treatment with pembrolizumab prolongs overall survival while PD-L1 expression and advanced stage emerge as poor prognostic factors in NSCLC patients. KRAS mutations may affect tumour microenvironment and patient's response to immunotherapy. Immune checkpoint inhibitors could represent an alternative therapeutic option for KRAS mutant NSCLC patients. Further investigation into this notion is warranted in order to validate the abovementioned observation.
Main subject category:
Health Sciences
Keywords:
NSCLC, PD-L1, Pembrolizumab, Immunotherapy
Number of references:
285
