TY - JOUR
T1 - Systemic Inflammatory Markers Combined with Tumor-Infiltrating Lymphocyte Density for the Improved Prediction of Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer
AU - Sawada, Ryuichiro
AU - Akiyoshi, Takashi
AU - Kitagawa, Yusuke
AU - Hiyoshi, Yukiharu
AU - Mukai, Toshiki
AU - Nagasaki, Toshiya
AU - Yamaguchi, Tomohiro
AU - Konishi, Tsuyoshi
AU - Yamamoto, Noriko
AU - Ueno, Masashi
AU - Fukunaga, Yosuke
N1 - Publisher Copyright:
© 2021, Society of Surgical Oncology.
PY - 2021/10
Y1 - 2021/10
N2 - Background: Previous studies have reported the utility of systemic inflammatory markers and CD8+ tumor-infiltrating lymphocyte (TIL) separately in predicting response to chemoradiotherapy (CRT) in rectal cancer; however, the efficacy of combining these markers remains unclear. Objective: This study aimed to elucidate the predictive efficacy of systemic inflammatory markers combined with CD8+ TIL density on response to neoadjuvant CRT in locally advanced rectal cancer. Methods: Ten systemic inflammatory markers and CD8+ TIL density were assessed in 267 patients with rectal cancer using pretreatment clinical data and biopsy samples. Response to CRT was determined using the Dworak tumor regression grade (TRG), with good responders classified as TRG3–4. Results: Receiver operating characteristic curve analysis showed high areas under the curve for the lymphocyte-to-C-reactive protein ratio (LCR) and neutrophil × monocyte (N × M) value (0.58 and 0.62, respectively). In the multivariate analysis, LCR, N × M value, and CD8+ TIL density were independently associated with good responders (p = 0.016, 0.005, and 0.002, respectively). Stratified analysis with these three markers showed a positive correlation between TRG3–4 ratio and the number of positive predictive factors (8.2%, 20.0%, 34.2%, and 59.1% in patients with 0, 1, 2, and 3 predictors, respectively). Overall and disease-free survival were significantly worse in patients with zero factors present compared with those with one to three factors present. Conclusions: LCR, N × M value, and CD8+ TIL density are independently associated with response to CRT. Assessing local TIL density along with systemic inflammatory markers may be useful for selecting a multimodal neoadjuvant approach in rectal cancer therapy.
AB - Background: Previous studies have reported the utility of systemic inflammatory markers and CD8+ tumor-infiltrating lymphocyte (TIL) separately in predicting response to chemoradiotherapy (CRT) in rectal cancer; however, the efficacy of combining these markers remains unclear. Objective: This study aimed to elucidate the predictive efficacy of systemic inflammatory markers combined with CD8+ TIL density on response to neoadjuvant CRT in locally advanced rectal cancer. Methods: Ten systemic inflammatory markers and CD8+ TIL density were assessed in 267 patients with rectal cancer using pretreatment clinical data and biopsy samples. Response to CRT was determined using the Dworak tumor regression grade (TRG), with good responders classified as TRG3–4. Results: Receiver operating characteristic curve analysis showed high areas under the curve for the lymphocyte-to-C-reactive protein ratio (LCR) and neutrophil × monocyte (N × M) value (0.58 and 0.62, respectively). In the multivariate analysis, LCR, N × M value, and CD8+ TIL density were independently associated with good responders (p = 0.016, 0.005, and 0.002, respectively). Stratified analysis with these three markers showed a positive correlation between TRG3–4 ratio and the number of positive predictive factors (8.2%, 20.0%, 34.2%, and 59.1% in patients with 0, 1, 2, and 3 predictors, respectively). Overall and disease-free survival were significantly worse in patients with zero factors present compared with those with one to three factors present. Conclusions: LCR, N × M value, and CD8+ TIL density are independently associated with response to CRT. Assessing local TIL density along with systemic inflammatory markers may be useful for selecting a multimodal neoadjuvant approach in rectal cancer therapy.
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U2 - 10.1245/s10434-021-09975-z
DO - 10.1245/s10434-021-09975-z
M3 - Article
C2 - 33876358
AN - SCOPUS:85104515508
SN - 1068-9265
VL - 28
SP - 6189
EP - 6198
JO - Annals of surgical oncology
JF - Annals of surgical oncology
IS - 11
ER -