Ryuichiro Sawada1, Takashi Akiyoshi2, Yusuke Kitagawa1, Yukiharu Hiyoshi1, Toshiki Mukai1, Toshiya Nagasaki1, Tomohiro Yamaguchi1, Tsuyoshi Konishi3, Noriko Yamamoto4, Masashi Ueno5, Yosuke Fukunaga1. 1. Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. 2. Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. takashi.akiyoshi@jfcr.or.jp. 3. Department of Colon and Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 4. Department of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan. 5. Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan.
Abstract
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.
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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