Prognostic Importance Of The Use Of Glucocorticoids And Antibiotics During The Neoadjuvant Radiotherapy Treatment In Locally Advanced Rectal Cancer: An Observational Study

Abstract

There is growing evidence that tumor-specific immune responses play an important role in anti-cancer therapy, including radiotherapy. Current studies have reported that the use of glucocorticoids and antibiotics therapy is associated with a reduced response to immune checkpoint inhibitors (ICIs) in routine practice. The purpose of this study was to evaluate whether there is an association between antibiotics and glucocorticoids administered during neoadjuvant radiotherapy (NRT) and prognosis in patients with local advanced rectal cancer (LARC) in routine clinical practice. We reviewed patients with pathologically confirmed LARC undergoing NRT followed by surgery in our department between January 2012 and April 2017. Collect patients' medication for glucocorticoids and antibiotics from the beginning of treatment and before surgery by consulting the electronic medical advice system. The patients were divided into four groups according to the time of the first glucocorticoids medication: no medication (noGC), before the start of NRT (bNRT), the first half of total NRT treatment time (fNRT), and the second half of total NRT treatment time until the operation (sNRT). We investigated whether glucocorticoids and antibiotics therapy administered during 30 days before NRT therapy until surgery was associated with overall survival (OS) and disease-free survival (DFS). Among 793 LARC patients (504 men and 289 women; median [range] age, 56 [49-63] years) with glucocorticoids therapy (n = 344, 43.3%) and antibiotics therapy (n = 320, 40.3%). Multivariate cox proportional hazards model analysis demonstrated that glucocorticoid therapy was associated with worse OS (hazard ratio [HR], 1.652; 95%CI, 1.115-2.447) and DFS (HR, 1.490; 95%CI, 1.028-2.160), but there were no significant differences in OS and DFS among patients with antibiotics therapy or not. Furthermore, there were significant differences in OS (HR, 2.071; 95%CI, 1.303-3.290, p = 0.002) among patients with glucocorticoid therapy in fNRT vs. noGC, but not in bNRT or fNRqazwT vs. noGC. fNRT vs. noGC. The dose of glucocorticoids was significantly associated with the DFS (HR, 1.935; 95%CI, 1.188-3.151, p = 0.008) in ≥35mg vs. noGC, but not in <35mg vs. noGC. Multivariate analyses confirmed that glucocorticoid therapy in fNRT was associated with worse OS (HR, 1.790; 95%CI, 1.186-2,701, p = 0.006) and high dose (≥35mg) were also associated with worse DFS (HR, 1.736; 95%CI, 1.105-2.728, p = 0.017) as potential independent prognostic factors. This study suggests that glucocorticoid therapy but not antibiotics therapy is associated with a worse OS and DFS in LARC patients in routine clinical practice. Glucocorticoid therapy in fNRT and high dose (≥35mg) are independent risk factors for OS and DFS, respectively. Mechanistic studies are urgently required to investigate glucocorticoids-mediated alterations of the immune response as a determinant of poorer outcome following NRT treatment.