Association of immunologic markers from complete blood counts with the response to preoperative chemoradiotherapy and prognosis in locally advanced rectal cancer

Jung, Sung Woo; Park, In Ja; Oh, Se Heon; Yeom, Seung-Seop; Lee, Jong Lyul; Yoon, Yong Sik; Kim, Chan Wook; Lim, Seok‐Byung; Lee, Jung Bok; Yu, Chang Sik; Kim, Jin Cheon

doi:10.18632/oncotarget.15760

Cited by 29 publications

(31 citation statements)

References 29 publications

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“…However, the predictive role of NLR in LARC patients remains unclear. Jung et al 29 . reported that pre-CRT NLR was not able to distinguish recurrence-free patients with rectal cancer receiving NCRT.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of pretreatment systemic inflammatory markers in patients with locally advanced rectal cancer following neoadjuvant chemoradiotherapy

Zhang

Liu

et al. 2020

Sci Rep

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The aim of this study was to explore the most powerful systemic inflammation marker of survival in locally advanced rectal cancer (LARC) patients and construct prognostic nomograms. A total of 472 LARC patients undergoing neoadjuvant chemoradiotherapy (NCRT) and radical surgery from 2011 to 2015 were included. The optimal cutoff points for the systemic immune-inflammation index (SII); and neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and monocyte-to-lymphocyte (MLR) ratios were calculated and determined by using the X-tile program. The cutoff values were 797.6. 2.3, 169.5, and 0.4, respectively. Cox regression analysis demonstrated that higher pathological TNM stage, the AJCC tumor regression grade, and the NLR level were significantly associated with increased overall survival and disease-free survival. High NLR level (≥ 2.3) was associated with higher pre-NCRT CA19-9 levels, lower hemoglobin, larger tumor size, and more lymph nodes retrieved (p = 0.012, p = 0.024, and p < 0.001; p < 0.001, respectively). High NRL scores were associated with poorer 5-year diseasefree survival and overall survival (p < 0.001, and p < 0.001, respectively). Predictive nomograms and time-independent receiver operating characteristic (ROC) curve that included the NLR score group were superior to those without NLR scores. Higher NLR scores (≥2 0.3) were associated with poorer DFS and OS in LARC patients. In addition, NLR was identified as the most effective marker for systemic inflammation, and the prognostic value was further confirmed by time-dependent ROC analysis. More intense adjuvant treatment could be considered for higher nLR score patients with LARc following ncRt. The standard of care for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (NCRT) followed by total mesorectal excision (TME). This strategy offers a higher probability of tumor downsizing and downstaging, increased tumor resectability, and better local tumor control 1-3. However, patients show a wide variation in responses to NCRT and thus, different oncological outcomes. Currently, it remains difficult to accurately predict treatment outcomes for LARC patients after NCRT. The identification of reliable biomarkers for the oncologic outcomes is important to assist in risk-adapted treatment strategies and subsequent surveillance. The systematic inflammatory response is involved in the development, progression, treatment response, and prognosis of many cancers, including prostate, breast, and colorectal cancers (CRC) 4-6. Accumulating evidence has demonstrated an association of systematic inflammation and resistance to radiotherapy and chemotherapy in CRC 7-9. The systematic inflammatory response can be reflected by hematological parameters, including the systemic immune-inflammation index (SII), the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the monocyte-to-lymphocyte ratio (MLR). Several studies have revealed that the hematological inflammatory markers could be predictive markers for oncolo...

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Section: Discussionmentioning

confidence: 99%

Prognostic value of pretreatment systemic inflammatory markers in patients with locally advanced rectal cancer following neoadjuvant chemoradiotherapy

Zhang

Liu

et al. 2020

Sci Rep

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“…Indeed, many clinicopathological and molecular factors have been suggested to be associated with pCR, although their utility in clinical practice remains controversial. 5 – 8 …”

Section: Introductionmentioning

confidence: 99%

Density of CD8+ lymphocytes in biopsy samples combined with the circulating lymphocyte ratio predicts pathologic complete response to chemoradiotherapy for rectal cancer

Xiao¹,

Peng²,

Zhang³

et al. 2017

CMAR

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ObjectivesThe systemic status and local immune status, as determined by the neutrophil–lymphocyte ratio (NLR) or the lymphocyte ratio (LYMR) and tumor-infiltrating lymphocyte (TIL) count, respectively, have been suggested as predictors of the tumor response to neoadjuvant chemoradiotherapy (nCRT) in rectal cancer, although the utility of these measures remains controversial. We aimed to investigate the values of the LYMR, NLR and TIL count and their combinations (TIL–LYMR/TIL–NLR) in predicting pathologic complete response (pCR) after nCRT.Patients and methodsPretreatment biopsy samples and data from the blood tests of 92 patients with rectal cancer who underwent curative resection after nCRT were retrospectively obtained. CD8+ TILs were immunostained using an antibody against CD8. The density of CD8+ TILs was recorded as the number of CD8+ T cells per square millimeter, and the results were classified as either “high” or “low”. The LYMR and NLR were calculated using pretreatment blood test data and categorized into either “high” or “low” groups. TIL–LYMR was graded as “low,” “mid” or “high” when neither, one or both the CD8+ TIL count and LYMR were “high,” respectively. TIL–NLR was graded similarly. The associations between TILs and LYMR, NLR and their combinations (TIL–LYMR/TIL–NLR) were evaluated.ResultspCR was significantly associated with a high LYMR, a low NLR and increased chemotherapy cycles (P=0.039, P=0.043 and P=0.015, respectively), but not with the CD8+ TIL count or carcinoembryonic antigen (CEA) level (P=0.100 and P=0.590, respectively). Additionally, 40% of patients with high LYMR and 40.7% with low NLR achieved pCR, whereas only 19.7% with low LYMR and 20.3% with high NLR did so. When the combinations were assessed, TIL–LYMR showed a positive correlation with pCR (P=0.038), while no association between TIL–NLR and pCR was found (P=0.916). In multivariate analysis, TIL–LYMR remained an independent predictor of pCR (odds ratio [OR]=1.833, 95% confidence interval [CI]=1.069–3.142, P=0.028).ConclusionHigh LYMR, low NLR and high TIL–LYMR at baseline are predictive of pCR to nCRT for patients with rectal cancer. These parameters may help identify pCR patients and provide additional information for therapeutic decision-making.

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“…Jung et al reported that patients with rectal cancer and high LMR, high PLR, or low NLR were associated with increased RFS, and high PLR was an independent marker for RFS after surgery following nCRT. However, no relationship to tumor response was found [23]. In the current study, we analyzed the relationships between PLR and treatment outcomes (tumor response, RFS) but did not find an association.…”

Section: Discussionmentioning

confidence: 76%

“…However, the NLR cutoff values used in previous studies of patients with rectal cancer that underwent nCRT were inconsistent. Some studies used historical values from other primary or metastatic cancers [12, 20, 25], and other studies used cutoff values calculated by statistical methods [23, 26, 27]. In the current study, cutoff values were determined after calculation by statistical methods.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil to Lymphocyte Ratio: A Predictive Marker for Treatment Outcomes in Patients With Rectal Cancer Who Underwent Neoadjuvant Chemoradiation Followed by Surgery

et al. 2019

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Purpose In this study, we investigated the role of neutrophil to lymphocyte ratio (NLR) as a predictor of tumor response and as a prognostic factor in patients with rectal cancer who had undergone curative surgery after neoadjuvant chemoradiation therapy (nCRT). Methods Between January 2009 and July 2016, we collected 140 consecutive patients who had undergone curative intent surgery after nCRT due to rectal adenocarcinoma. We obtained the pre- and post-nCRT NLR by dividing the neutrophil count by the lymphocyte count. The cutoff value was obtained using receiver operating characteristic analysis for tumor response and using maximally selected rank analysis for recurrence-free survival (RFS). The relationship among NLR, tumor response, and RFS was assessed by adjusting the possible clinico-pathological confounding factors. Results The possibility of pathologic complete response (pCR) was significantly decreased in high pre- (>2.77) and postnCRT NLR (>3.23) in univariate regression analysis. In multivariate analysis, high post-nCRT NLR was an independent negative predictive factor for pCR (adjusted odds ratio, 0.365; 95% confidence interval [CI], 0.145–0.918). The 5-year RFS of all patients was 74.6% during the median 37 months of follow-up. Patients with higher pre- (>2.66) and post-nCRT NLR (>5.21) showed lower 5-year RFS rates (53.1 vs. 83.3%, P = 0.006) (69.2 vs. 75.7%, P = 0.054). In multivariate Cox analysis, high pre-nCRT NLR was an independent poor prognostic factor for RFS (adjusted hazard ratio, 2.300; 95% CI, 1.061–4.985). Conclusion Elevated NLR was a negative predictive marker for pCR and was independently associated with decreased RFS. For confirmation, a large-scale study with appropriate controls is needed.

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Association of immunologic markers from complete blood counts with the response to preoperative chemoradiotherapy and prognosis in locally advanced rectal cancer

Cited by 29 publications

References 29 publications

Prognostic value of pretreatment systemic inflammatory markers in patients with locally advanced rectal cancer following neoadjuvant chemoradiotherapy

Prognostic value of pretreatment systemic inflammatory markers in patients with locally advanced rectal cancer following neoadjuvant chemoradiotherapy

Density of CD8+ lymphocytes in biopsy samples combined with the circulating lymphocyte ratio predicts pathologic complete response to chemoradiotherapy for rectal cancer

Neutrophil to Lymphocyte Ratio: A Predictive Marker for Treatment Outcomes in Patients With Rectal Cancer Who Underwent Neoadjuvant Chemoradiation Followed by Surgery

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