Optimization of combined treatment for locally advanced distal rectal cancer with regard to prognosis factors

April 16, 2020
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The current concept of neoadjuvant chemoradiotherapy (NCRT), as a key method in achieving complete or partial tumor’s radiological response to therapy enables to improve the immediate and long-term results of rectal cancer treatment. The purpose of this study was to define prognostic factors for the effectiveness of NCRT in achieving a tumor-radiological response on therapy in patients with local advanced distal rectal cancer (LADRC), as well as factors to prognosion free survival using molecular 8-oxo-2’-deoxyguanosine (8-оксо-dG), immunohistochemical (Ki67) and molecular genetics (GSTP1 and MTHFR genes polymorphism) markers. Materials and methods. GSTP1 and MTHFR gene polymorphisms were determined in real-time on tumor material obtained from 110 patients with LADRC by real-time allele-specific polymerase chain reaction. Level of the 8-оксо-dG in the eluate was performed with spectrophotometric method. Immunohistochemical studies of the Ki-67, MutS 2–6, CD44, and CEA markers were carried out according to standard methods. Results. In patients with LADRC from both study groups, there were significant pathological responses of the tumor to NCRT: in the comparison group it was 47.2%, in the main group — 59.7% suitably to the mrTRG scale and 49.1% and 64.9% with RECIST 1.1 criteria, respectively. It was found that oxaliplatin-containing chemotherapy promotes statistically significant decrease in 8-оксо-dG’s level. The use of single capacetabine in neoadjuvant regimen for patients with LADRC in presence as A313G GSTP1 and C667T MTHFR polymorphisms does not affect increase on relapse-free survival. When combined GSTP1, MTFR and Ki67 factors they are determined predicted probability of recurrence in this patients within 51–99%. Conclusion. The use of capacetabine in NCRT for patients with LADRC is effective only in absence of polymorphisms A313G GSTP1 and C667T MTHFR, in other cases it is desirable to use as NCRT scheme CAPOX. 8-оксо-dG reduction level can serve as independent prognostic factor of NCRT efficacy.

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