TY - JOUR
T1 - Immunogenetic markers in IL17F predict the risk of metastases spread and overall survival in rectal cancer patients treated with neoadjuvant chemoradiotherapy
AU - Cecchin, Erika
AU - De Mattia, Elena
AU - Dreussi, Eva
AU - Montico, Marcella
AU - Palazzari, Elisa
AU - Navarria, Federico
AU - Bergamo, Francesca
AU - Belluco, Claudio
AU - Quartuccio, Luca
AU - De Vita, Salvatore
AU - Canzonieri, Vincenzo
AU - Gagno, Sara
AU - Zanusso, Chiara
AU - Buonadonna, Angela
AU - Pucciarelli, Salvatore
AU - De Paoli, Antonino
AU - Toffoli, Giuseppe
N1 - Funding Information:
This study was supported by Italian Ministry of Health grant (Ricerca Finalizzata FSN2014 , RF-2011-02349645 , CUP:J92I14000180001 ).
Publisher Copyright:
© 2020 Elsevier B.V.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/8
Y1 - 2020/8
N2 - Background and purpose: The role of the immune system in tumor response to chemo-radiotherapy (CRT) is an emerging issue. This work aimed at identifying predictive and prognostic immunogenetic variants in LARC patients after preoperative (po)-CRT and surgery. Materials and methods: A set of 192 polymorphisms in 34 candidate genes involved in the regulation of the immune response signalling network, was selected and analyzed in 370 LARC patients treated with po-CRT and surgery, split into a Test Set (n = 233) and a Validation Set (n = 137). Immunogenetic markers were selected based on a concordant significant effect on 2-year relapse-free survival (2-yrRFS) (bootstrapped P < 0.05) in both patients Sets. The effect of the selected immunogenetic variants on 5-year metastases-free (5yrMFS), 5-year disease-free (5yrDFS), and 10-year overall (10yrOS) survival was tested in the entire Set of 370 patients. Results: Two immunogenetic IL17F (IL17F-rs641701 and IL17F-rs9463772) markers predictive of 2yrRFS, 5yrDFS, 5yrMFS, and 10yrOS were identified. The combination of tumor regression grade (TRG) and patients genotype for IL17F-rs641701 and IL17F-rs9463772 allowed the identification of subgroups of patients with differential prognosis in term of both 5yrDFS (HR 11.29, P-value <0.001, and HR 5.86, P-value = 0.001, respectively) and 10yrOS (HR 7.07, P-value = 0.005, and HR 6.05, P-value = 0.002, respectively). Conclusion: IL17F-rs641701 and IL17F-rs9463772 were highlighted as promising immunogenetic markers significantly associated with the prognosis of LARC patients. After a prospective validation of the herein reported findings, the combination of TRG and patients genotype should be considered to provide additional stratification criteria for the selection of a personalized multimodality treatment.
AB - Background and purpose: The role of the immune system in tumor response to chemo-radiotherapy (CRT) is an emerging issue. This work aimed at identifying predictive and prognostic immunogenetic variants in LARC patients after preoperative (po)-CRT and surgery. Materials and methods: A set of 192 polymorphisms in 34 candidate genes involved in the regulation of the immune response signalling network, was selected and analyzed in 370 LARC patients treated with po-CRT and surgery, split into a Test Set (n = 233) and a Validation Set (n = 137). Immunogenetic markers were selected based on a concordant significant effect on 2-year relapse-free survival (2-yrRFS) (bootstrapped P < 0.05) in both patients Sets. The effect of the selected immunogenetic variants on 5-year metastases-free (5yrMFS), 5-year disease-free (5yrDFS), and 10-year overall (10yrOS) survival was tested in the entire Set of 370 patients. Results: Two immunogenetic IL17F (IL17F-rs641701 and IL17F-rs9463772) markers predictive of 2yrRFS, 5yrDFS, 5yrMFS, and 10yrOS were identified. The combination of tumor regression grade (TRG) and patients genotype for IL17F-rs641701 and IL17F-rs9463772 allowed the identification of subgroups of patients with differential prognosis in term of both 5yrDFS (HR 11.29, P-value <0.001, and HR 5.86, P-value = 0.001, respectively) and 10yrOS (HR 7.07, P-value = 0.005, and HR 6.05, P-value = 0.002, respectively). Conclusion: IL17F-rs641701 and IL17F-rs9463772 were highlighted as promising immunogenetic markers significantly associated with the prognosis of LARC patients. After a prospective validation of the herein reported findings, the combination of TRG and patients genotype should be considered to provide additional stratification criteria for the selection of a personalized multimodality treatment.
KW - Fluoropyrimidines
KW - IL17F
KW - Immunogenetics
KW - Neo-adjuvant chemo-radiotherapy
KW - Polymorphisms
KW - Rectal cancer
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U2 - 10.1016/j.radonc.2020.04.055
DO - 10.1016/j.radonc.2020.04.055
M3 - Article
C2 - 32387487
AN - SCOPUS:85084764857
VL - 149
SP - 30
EP - 37
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
SN - 0167-8140
ER -