TY - JOUR
TI - Predicting the role of dna polymerase β alone or with kras mutations in advanced nsclc patients receiving platinum-based chemotherapy
AU - Alvisi, M.F.
AU - Ganzinelli, M.
AU - Linardou, H.
AU - Caiola, E.
AU - Russo, G.L.
AU - Cecere, F.L.
AU - Bettini, A.C.
AU - Psyrri, A.
AU - Milella, M.
AU - Rulli, E.
AU - Fabbri, A.
AU - De Maglie, M.
AU - Romanelli, P.
AU - Murray, S.
AU - Ndembe, G.
AU - Broggini, M.
AU - Garassino, M.C.
AU - Marabese, M.
JO - Journal of Clinical Medicine Research
PY - 2020
VL - 9
TODO - 8
SP - 1-10
PB - MDPI
SN - 1918-3003, 1918-3011
TODO - 10.3390/jcm9082438
TODO - biological marker;  carboplatin;  cisplatin;  DNA directed DNA polymerase beta;  gemcitabine;  K ras protein;  pemetrexed;  platinum derivative;  vinorelbine tartrate, adult;  aged;  Article;  cancer prognosis;  chemoradiotherapy;  controlled study;  DNA extraction;  female;  gene mutation;  genetic analysis;  genotype;  histology;  human;  human tissue;  immunohistochemistry;  major clinical study;  male;  multicenter study;  non small cell lung cancer;  overall survival;  polymerase chain reaction;  progression free survival;  prospective study;  protein expression;  Sanger sequencing
TODO - Clinical data suggest that only a subgroup of non-small cell lung cancer (NSCLC) patients has long-term benefits after front-line platinum-based therapy. We prospectively investigate whether KRAS status and DNA polymerase β expression could help identify patients responding to platinum compounds. Prospectively enrolled, advanced NSCLC patients treated with a first-line regimen containing platinum were genotyped for KRAS and centrally evaluated for DNA polymerase β expression. Overall survival (OS), progression-free survival (PFS), and the objective response rate (ORR) were recorded. Patients with KRAS mutations had worse OS (hazard ratio (HR): 1.37, 95% confidence interval (95% CI): 0.70–2.27). Negative DNA polymerase β staining identified a subgroup with worse OS than patients expressing the protein (HR: 1.43, 95% CI: 0.57–3.57). The addition of KRAS to the analyses further worsened the prognosis of patients with negative DNA polymerase β staining (HR: 1.67, 95% CI: 0.52–5.56). DNA polymerase β did not influence PFS and ORR. KRAS may have a negative role in platinum-based therapy responses in NSCLC, but its impact is limited. DNA polymerase β, when not expressed, might indicate a group of patients with poor outcomes. KRAS mutations in tumors not expressing DNA polymerase β further worsens survival. Therefore, these two biomarkers together might well identify patients for whom alternatives to platinum-based chemotherapy should be used. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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