Yoon, H.H.Catalano, P.Gibson, M.K.Skaar, Todd C.Philips, S.Montgomery, E.A.Hafez, M.J.Powell, M.Liu, G.Forastiere, A.A.Benson, A.B.Kleinberg, L.R.Murphy, K.M.2022-10-102022-10-102011-10Yoon, H. H., Catalano, P., Gibson, M. K., Skaar, T. C., Philips, S., Montgomery, E. A., Hafez, M. J., Powell, M., Liu, G., Forastiere, A. A., Benson, A. B., Kleinberg, L. R., & Murphy, K. M. (2011). Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: Results from the Eastern Cooperative Oncology Group. Cancer Chemotherapy and Pharmacology, 68(4), 863–870. https://doi.org/10.1007/s00280-011-1556-5https://hdl.handle.net/1805/30290PURPOSE: Germline genetic variations may partly explain the clinical observation that normal tissue tolerance to radiochemotherapy varies by individual. Our objective was to evaluate the association between single-nucleotide polymorphisms (SNPs) in radiation/platinum pathways and serious treatment-related toxicity in subjects with esophageal adenocarcinoma who received cisplatin-based preoperative radiochemotherapy. METHODS: In a multicenter clinical trial (E1201), 81 eligible treatment-naïve subjects with resectable esophageal adenocarcinoma received cisplatin-based chemotherapy concurrent with radiotherapy, with planned subsequent surgical resection. Toxicity endpoints were defined as grade ≥3 radiation-related or myelosuppressive events probably or definitely related to therapy, occurring during or up to 6 weeks following the completion of radiochemotherapy. SNPs were analyzed in 60 subjects in pathways related to nucleotide/base excision- or double stranded break repair, or platinum influx, efflux, or detoxification. RESULTS: Grade ≥3 radiation-related toxicity (mostly dysphagia) and myelosuppression occurred in 18 and 33% of subjects, respectively. The variant alleles of the XRCC2 5' flanking SNP (detected in 28% of subjects) and of GST-Pi Ile-105-Val (detected in 65% of subjects) were each associated with higher odds of serious radiation-related toxicity compared to the major allele homozygote (47% vs. 9%, and 31% vs. 0%, respectively; P = 0.005). No SNP was associated with myelosuppression. CONCLUSIONS: This novel finding in a well-characterized cohort with robust endpoint data supports further investigation of XRCC2 and GST-Pi as potential predictors of radiation toxicity.enAdenocarcinomaAntineoplastic AgentsCisplatinChemoradiationSingle Nucleotide PolymorphismEsophageal CancerArticle