Abstract
Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the standard treatment for locally advanced rectal cancer. Here, we analyzed the impact of local and systemic environments on the tumor response to preoperative chemoradiotherapy in rectal cancer. We recruited 141 patients with rectal cancer treated with nCRT. We evaluated the local tumor environment, including tumor-infiltrating lymphocytes (TILs), intratumor budding (ITB), and the systemic inflammatory environment, including the neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) level. Our finding revealed that tumor regression was significantly associated with the density of CD8+ TILs in the intraepithelial, the presence of ITB, the combination of NLR and CRP (NLR-CRP) value, and the combination of CD8+ intraepithelial TIL (iTIL) density and ITB presence. Moreover, multivariate analysis showed that only the combination of CD8+ iTILs and ITB was an independent predictive factor for the pathological response to nCRT in rectal cancer. Our finding demonstrate that the local tumor environment was a better predictor of the tumor response than the systemic environment and thus provided new insight into screening for patients who are more likely to benefit from cancer treatment.
Highlights
Colorectal cancer remains one of the leading causes of cancer death worldwide [1]
Tumor microenvironment-related variables, including the CD8+ intraepithelial tumor-infiltrating lymphocyte (TIL) (iTIL) density and intratumor budding (ITB), and systemic inflammatory response-related factors (i.e., neutrophil-to-lymphocyte ratio (NLR)-C-reactive protein (CRP)), were significantly correlated with tumor regression
Multivariate regression analysis showed that only the combination of CD8+ iTIL density and ITB was an independent factor for tumor regression, indicating that the local tumor environment is a better predictor of the pathological response to neoadjuvant chemoradiotherapy (nCRT) than is the systemic inflammatory response
Summary
In patients with locally advanced rectal cancer (stage II and III), neoadjuvant chemoradiotherapy (nCRT) could significantly reduce the local recurrence and treatment-associated toxicity, and more importantly, make tumors more amenable to resection [2]. The tumor response to nCRT varies greatly among patients. 8–14% of patients attain a pathologic complete response (PCR), and watchful waiting is proposed [3]. 20% of these patients will not respond to nCRT and will even suffer significant side effects and miss their best opportunity for surgery. Evidence of the correlation between PCR and both long-term disease-free survival and overall survival is emerging [4]. Finding effective approaches for predicting the treatment response and further selecting populations who are likely to benefit most from nCRT is urgent
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