TY - JOUR
T1 - High expression of krüppel-like factor 10 or Smad4 predicts clinical benefit of adjuvant chemoradiotherapy in curatively resected pancreatic adenocarcinoma
T2 - From a randomized phase III trial
AU - Pen, Shu Ling
AU - Shan, Yan Shen
AU - Hsiao, Chin Fu
AU - Liu, Tsang Wu
AU - Chen, Jen Shi
AU - Ho, Ching Liang
AU - Chou, Wen Chi
AU - Hsieh, Ruey Kuen
AU - Chen, Li Tzong
AU - Ch'ang, Hui Ju
N1 - Funding Information:
This study was supported by National Health Research Institutes grant (CA-102 ~ 107-PP27)
Funding Information:
We thank all the hospitals that enrolled patients and collected tissues for this trial. We are grateful to the patients who participated in the study and their family for making this study possible. We thank research technicians, nurses, and statisticians from TCOG. In particular, we would like to thank Mr. Chao-Tung Lee, Ms. Suwen Nieh, and Dr. Chang Chen for their tremendous efforts in comprehensive statistical analyses, immunohistochemical works, and pathologic interpretation, respectively, for this trial. All data generated and analyzed during this study are included in this published article (and its supplementary information files). Patient-level data for this study are available at: ClinicalTrials.gov. identifier: NCT01666184. JSC reports research funding from companies including: ONO Pharmaceutica, MSD Oncology, MedImmune, Lilly, TTY Biopharm, Daiichi Sankyo, orient EuroPharma. LTC reports research funding companies including: Novartis, Merck, Serono, TTY, Polaris, SyncorePharm, Pfizer, BMS; Honoraria of ONO, Eli Lilly, MSD, PharmaEngine, TTY, SyncorePharm, Novartis, Astra Zeneca, Ipsen; Patents & Royalties of ENO-1mAb/HuniLife; Membership on Board of Directors ScinoPharm. Taiwan, Ltd. and on Scientific Advisory Committee of PharmaEngine. All remaining authors have declared no conflicts of interest.
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/5
Y1 - 2021/5
N2 - Purpose: Our previous studies have demonstrated that Krüppel-like factor 10 (Klf10) modulated tumor radiation resistance and helps to predict clinical outcomes of pancreatic adenocarcinoma (PDAC). This study aimed to evaluate whether the expression levels of Klf10, Smad4 and Runx3 can help predict the benefits of adjuvant chemoradiotherapy (CRT) in resected PDAC. Methods and materials: Tissue specimens were collected from 111 patients with curatively resected PDAC who were enrolled into a randomized trial comparing adjuvant gemcitabine with or without CRT. Immunohistochemical expression of biomarkers was quantified by pathologists blinded to patient outcomes through a grading system based on the extent and intensity of staining. The predictive value of biomarkers was analyzed using SAS statistical software. Results: In total, 56 and 55 patients received adjuvant gemcitabine alone and additional CRT, respectively. The expression levels of Klf10, Smad4 and postoperative CA19-9 were significantly correlated with overall survival (OS) (p = 0.013, 0.045, and 0.047, respectively). Multivariable analysis showed that the expression level of postoperative serum CA19-9 and tumor tissue Klf10 expression level were significant predictors for OS (p = 0.038, and 0.028, respectively). Patients with high Klf10 or Smad4 (n = 55), had a significantly better local recurrence-free survival (∞ vs 19.8 months; p = 0.026) and a longer OS (33.0 vs 23.0 months; p = 0.12) if they received additional adjuvant CRT than gemcitabine only. The results were similar after adjusted by postoperative level of CA19-9. Conclusion: Patients with curatively resected PDAC and a high expression of either Klf10 or Smad4 have high chances of benefiting from adjuvant CRT. Combining Klf10 and Smad4 to predict the benefits of adjuvant CRT in resected PDAC deserves further validation.
AB - Purpose: Our previous studies have demonstrated that Krüppel-like factor 10 (Klf10) modulated tumor radiation resistance and helps to predict clinical outcomes of pancreatic adenocarcinoma (PDAC). This study aimed to evaluate whether the expression levels of Klf10, Smad4 and Runx3 can help predict the benefits of adjuvant chemoradiotherapy (CRT) in resected PDAC. Methods and materials: Tissue specimens were collected from 111 patients with curatively resected PDAC who were enrolled into a randomized trial comparing adjuvant gemcitabine with or without CRT. Immunohistochemical expression of biomarkers was quantified by pathologists blinded to patient outcomes through a grading system based on the extent and intensity of staining. The predictive value of biomarkers was analyzed using SAS statistical software. Results: In total, 56 and 55 patients received adjuvant gemcitabine alone and additional CRT, respectively. The expression levels of Klf10, Smad4 and postoperative CA19-9 were significantly correlated with overall survival (OS) (p = 0.013, 0.045, and 0.047, respectively). Multivariable analysis showed that the expression level of postoperative serum CA19-9 and tumor tissue Klf10 expression level were significant predictors for OS (p = 0.038, and 0.028, respectively). Patients with high Klf10 or Smad4 (n = 55), had a significantly better local recurrence-free survival (∞ vs 19.8 months; p = 0.026) and a longer OS (33.0 vs 23.0 months; p = 0.12) if they received additional adjuvant CRT than gemcitabine only. The results were similar after adjusted by postoperative level of CA19-9. Conclusion: Patients with curatively resected PDAC and a high expression of either Klf10 or Smad4 have high chances of benefiting from adjuvant CRT. Combining Klf10 and Smad4 to predict the benefits of adjuvant CRT in resected PDAC deserves further validation.
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U2 - 10.1016/j.radonc.2021.02.037
DO - 10.1016/j.radonc.2021.02.037
M3 - Article
C2 - 33667587
AN - SCOPUS:85102301521
SN - 0167-8140
VL - 158
SP - 146
EP - 154
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
ER -