Associatie tussen genetische varianten en oesofagitis bij NSCLC-patiënten behandeld met platinahoudend chemotherapie en radiotherapie: een prospectieve observationele studie

Abstract

Association between genetic variants and esophagitis in patients with NSCLC treated with first-line platinum based (radio)therapy: a prospective observational study Background Lung cancer is prevalent in the Netherlands, with non-small cell lung cancer (NSCLC) accounting for 70% of all patients. Treatment typically involves chemo-, radio-, and/or immunotherapy. Toxicity, such as acute esopha-gitis, is common and often requires adjustments in the treatment regimen. Objective The primary objective was to explore genetic risk fac-tors for esophagitis in NSCLC patients undergoing platinum-based (radio)therapy. Secondary objectives included determining the incidence and severity of esophagitis and assessing whether patient characteris-tics and treatment regimens influence the risk of devel-oping esophagitis. Design and methods PGxLUNG is a multicenter prospective study and included 320 NSCLC patients (stage II-IV) treated with first-line platinum-based chemotherapy. Esophagitis was assessed regularly during follow-up using the Com-mon Terminology Criteria for Adverse Events (CTCAE) v4.03. The association between 28 single nucleotide polymorphisms (SNPs), selected based on literature, and esophagitis was analysed by multivariate logistic regression. Results The incidence of severe esophagitis is higher in patients undergoing chemoradiotherapy (24.5%) compared to those who did not receive radiotherapy (0.6%). Addi-tionally, severe esophagitis occurred 2.5 times more fre-quent in patients undergoing concurrent chemoradio-therapy compared to those receiving sequential chemo-radiotherapy. Significant associations with severe esoph-agitis were found for OGG1 (rs1052133), RPS6KB2 (rs10274), and ERCC2 (rs13181). Patients with the GG genotype for OGG1 showed a 7.6-fold higher risk, the AA genotype for RPS6KB2 a 3.2-fold increase, and the TT genotype for ERCC2 a 2.5-fold higher risk. The num-bers needed to genotype (NNG) were 45, 20, and 17, respectively. Conclusion Genetic variants in OGG1, RPS6KB2, and ERCC2 are associated with the risk of radiotherapy-induced esoph-agitis in NSCLC patients. Genotype-guided selection of a less burdensome radiotherapy regimen may be bene-ficial for patients with risk-associated genotypes.