Open Access

Systemic inflammatory indices predict tumor response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer

  • Authors:
    • Sicong Lai
    • Liang Huang
    • Shuangling Luo
    • Zhanzhen Liu
    • Jianghui Dong
    • Liping Wang
    • Liang Kang
  • View Affiliations

  • Published online on: July 3, 2020     https://doi.org/10.3892/ol.2020.11812
  • Pages: 2763-2770
  • Copyright: © Lai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Systemic inflammatory responses are associated with the prognosis of patients with colorectal cancer. However, the value in predicting tumor responses to neoadjuvant chemoradiotherapy (nCRT) remains to be elucidated. The current study aimed to investigate the association between systemic inflammatory indices and pathological complete response (pCR). The training and validation cohorts included 225 and 96 patients with locally advanced rectal cancer. The neutrophil‑to‑lymphocyte ratio (NLR) and platelet‑to‑lymphocyte ratio were recorded prior to nCRT and radical surgery. Univariate and multivariate analysis were used to investigate the association between systemic inflammatory indices and pCR. Systemic inflammatory indices prior to or following treatment had no significant association with pCR; however, the percentage change in NLR from pre‑nCRT to post‑nCRT was associated with a poor response, and a percentage change of >21.5% NLR (P=0.006; OR=0.413; 95% CI=0.22‑0.773) was a predictor of poor pCR. Therefore, in rectal cancer, the percentage change in NLR from pre‑ to post‑nCRT was found to be a predictor of poor pCR.

Introduction

Colorectal cancer has become one of the most common tumors and is the third most common malignancy. Globally, ~1.2 million patients are diagnosed with colorectal cancer and >600,000 die from the disease in 2008 (1). Neoadjuvant chemoradiotherapy (nCRT) prior to radical surgery and post-operative adjuvant chemotherapy is the standard treatment for locally advanced rectal cancer (LARC) (2,3). Certain complications can arise from radical surgery that decrease quality of life, including anastomotic leakage, anastomotic stenosis, urinary and/or sexual dysfunction, low anterior resection syndrome and increased probability of enterostomy (46).

Response to neoadjuvant therapy is heterogeneous and ~10-30% of patients with colorectal cancer achieve pathological complete response (pCR) (7). The ‘watch and wait’ strategy and local resection for patients with pCR following nCRT has become a focus of study (8,9). Generally, pCR is predicted through digital rectum examination, imaging examination, endoscopy and tumor-related markers (912). However, the predictions made using these techniques are not always in line with the pathology results (8,13). Currently, there are no affordable and reliable markers that can predict tumor response.

Systemic inflammatory responses have been reported to be predictors of prognosis for numerous types of solid tumors, including gastrointestinal (14,15), pancreatic (16), renal (17) and breast cancer (18). Systemic inflammatory responses can be reflected by hematologic parameters, including lymphocyte count and platelet count, or the ratio of different cell types, including the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) (19,20). The tumor microenvironment is closely associated with the occurrence and development of cancer (21). In the peripheral circulation, neutrophils and lymphocytes act as immunocytes, reflecting the tumor microenvironment, and the number of immunocytes changes according to patient age and immunoreactivity (22). Changes in the NLR may be associated with changes in tumor size during regression due to the nCRT for rectal cancers (23). However, it remains unclear whether systematic inflammatory responses could be used as a marker for identifying patients with tumors achieving pCR following nCRT.

Therefore, the current study investigated pre- and post-nCRT systemic inflammatory indices and changes in these indices from pre-nCRT to post-nCRT to determine the association between these parameters and responsiveness to nCRT in patients with LARC.

Materials and methods

Patients

Data from patients with rectal cancer who received nCRT and radical surgery at the Sixth Affiliated Hospital between January 2013 and October 2018, were retrospectively analyzed. A total of 321 patients were included in this study. The mean age of patients was 58.5 years. A total of 218 patients were male (67.9%) and 103 patients were female (32.1%). The inclusion criteria were as follows: i) 18–75 years old; ii) diagnosis of rectal adenocarcinoma confirmed by biopsy pathology; iii) stage II (T3/T4; N0M0) or stage III (T1-4; N+M0) evaluated by thoracic and abdominal pelvic CT, pelvic MRI or transluminal ultrasound prior to nCRT; iv) the distance from the anal verge evaluated by digital rectum examination or enteroscopy was <12 cm; v) an Eastern Cooperative Oncology Group score of 0–2; vi) (24) no radiotherapy, chemotherapy or surgical contraindications; and vii) no past medical history of malignant tumors. The exclusion criteria included the following: i) Absence of clinical data; ii) infections prior to new adjuvant therapy or surgery; iii) use of leukocyte enhancing drugs; and iv) incomplete new adjuvant therapy or radical surgery. Prior to the study, all patients provided written informed consent. The current study was approved by the Institutional Review Board of the Sixth Affiliated Hospital following rigorous review.

Treatment

All patients were assessed by a multiple disciplinary team at The Sixth Affiliated Hospital of Sun Yat-sen University and underwent nCRT and radical surgery. The total dose of radiotherapy given was 46–50.4, or 1.8–2.0 Gy for 23–28 fractions. Patients received one of the following two chemotherapy regimens: mFOLFOX6 [85 mg/m2 oxaliplatin, 400 mg/m2 leucovorin and 400 mg/m2 fluorouracil (5-FU) administered through intravenous drip on day 1, followed by 2,400 mg/m2 fluorouracil continuously administered through intravenous infusion for 48 h] or DeGramont (400 mg/m2 leucovorin, 400 mg/m2 F-5U administered through intravenous drip on day 1, followed by 2,400 mg/m2 fluorouracil continuously administered through intravenous infusion for 48 h). The interval between radiotherapy and surgery was 4–12 weeks and the interval between chemotherapy and surgery was 2–4 weeks.

Peripheral blood examinations

Peripheral blood (2 ml) was collected from all patients within 1 week prior to the first nCRT (pre-nCRT) and 1 week prior to surgery (post-nCRT). Neutrophil, lymphocyte and platelet counts were obtained from the hospital information system. The PLR was calculated as the absolute count of platelets/lymphocytes and NLR was calculated as the absolute count of neutrophils/lymphocytes. The percentage change in NLR from pre-nCRT to post-nCRT was defined as [(post-NLR-pre-NLR)/pre-NLR ×100%]. A result of ≥0 indicated that NLR following new adjuvant treatment was increased, whereas a result of <0 indicated that NLR after new adjuvant treatment was decreased. The percentage change in PLR from pre-nCRT to post-nCRT was defined as [(post-PLR-pre-PLR)/pre-PLR ×100%].

Pathological assessment

Two experienced pathologists evaluated the tumor regression grades (TRG) of patients based on the American Joint Committee on Cancer (AJCC; 8th edition) (25) as follows: 0, no viable cancer cells (complete response); 1, single cells or rare small groups of cancer cells (near-complete response); 2, residual cancer with evident tumor regression and with single cells or rare small groups of cancer cells (partial response); and 3, extensive residual cancer with no evident tumor regression (poor or no response), pCR was defined as no signs of viable cancer cells in resected specimens and in the lymph nodes.

Statistical analysis

SPSS software (version 24.0; IBM Corp.) was used to analyze data. P<0.05 was considered to indicate a statistically significant difference. The χ2 test was used to compare the differences between the qualitative variables of the cohorts. The Shapiro-Wilk test confirmed that the quantitative data did not conform to a normal distribution. Therefore, quantitative data between cohorts were compared by the Mann-Whitney U test. Tumor patients were strictly divided into a pCR group (TRG 0) and a non-pCR group (TRG 1–3) according to TRG stages. The ‘cut-off’ value of the indices was determined by the receiver operating characteristic curve (ROC). Parameters were compared using the χ2 and t-tests between pCR and non-pCR groups. The association between systemic inflammatory indices and pCR were analyzed by univariate and multivariate logistic regression analysis. The multivariate analysis included the variables of P<0.1 in the univariate analysis.

Results

Patient characteristics

Baseline characteristics of patients in the two cohorts are presented in Table 1. In the training cohort, a total of 152 patients were male (67.6%) and 73 patients were female (32.4%). A total of 162 (72%) patients received a chemotherapy regimen with oxaliplatin (mFOLFOX6). Furthermore, 69 patients (30.6%) achieved pCR. In the validation cohort, 66 patients (68.7%) were male and 30 patients (31.3%) were female. A total of 67 patients (69.8%) received chemotherapy regimens with oxaliplatin. There were 26 patients (27.1%) who achieved pCR. No statistical differences were observed in clinical characteristics, treatment factors and systemic inflammatory indices between the two cohorts (P>0.05).

Table I.

Baseline characteristics of the patients in the training and validation cohorts.

Table I.

Baseline characteristics of the patients in the training and validation cohorts.

VariableTraining cohortValidation cohortP-value
Age, years 0.670
  ≤6518380
  >654216
Sex 0.834
  Male15266
  Female7330
CEA prior to treatment, µg/l 0.621
  ≤513460
  >59136
Clinical T stage 0.977
  T283
  T316772
  T45021
Clinical N stage 0.574
  N03216
  N1-219380
Tumor size, cm 0.126
  ≤517366
  >55230
Tumor circumference, % 0.838
  ≤509140
  >5013456
Mesorectal fascia 0.659
  Positive7630
  Negative14966
Distance from anal verge, cm 0.280
  ≤512660
  >59936
Tumor differentiation 0.929
  High718
  Medium13356
  Low2132
Operation interval of radiotherapy, weeks 0.178
  ≤79332
  >713264
Chemotherapy regimens 0.689
  With oxaliplatin16267
  Without oxaliplatin6329
Chemotherapy courses 0.055
  ≤43021
  >419575
Tumor response 0.520
  pCR6926
  Non-pCR15670
Mean value of pre-NLR (interval)2.39 (0.59–17.04)2.52 (0.79–27.46)0.626
Mean value of pre-PLR (interval)148.57 (40.31–536.00)144.21 (47.92–448.84)0.596
Mean value of post-NLR (interval)3.66 (0.81–16.79)3.09 (0.77–12.99)0.078
Mean value of post-PLR (interval)237.63 (77.25–1007.07)220.87 (84.11–595.30)0.556
Mean value of percentage change in NLR, % (interval)80 (−81-1066)57 (−91-412)0.179
Mean value of percentage change in PLR, % (interval)74 (−73-605)69 (−60-343)0.614

[i] CEA, carcino-embryonic antigen; T, tumor; N, lymph node; pCR, pathological complete response; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio.

Analysis for pCR in the training cohort

Associations between systemic inflammation indices and pCR for the training cohort are presented in Table II. The mean value of the percentage change in NLR was 63% in the pCR group and 87% in the non-pCR group. Additionally, the percentage change in NLR was significantly increased in the pCR group compared with the non-pCR group (P=0.036; Fig. 1). However, there were no significant differences in the other pre- and post-treatment systemic inflammation indices between the pCR and non-pCR group.

Table II.

Association between systemic inflammatory indices and pCR in the training cohort.

Table II.

Association between systemic inflammatory indices and pCR in the training cohort.

Variable (mean)pCR Group (n=69)Non-pCR Group (n=156)P-value
Pre-NLR2.552.320.234
Pre-PLR157.30144.710.302
Post-NLR3.343.800.071
Post-PLR232.40239.940.761
% change in NLR63870.036
% change in PLR61800.170

[i] pCR, pathological complete response; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio.

The area under the curve of the ROC analysis was 0.588 (P=0.036; Fig. 2). Therefore, we divided the percentage change in NLR into two categories for subsequent analyses: A percentage change of ≤21.5% NLR and a percentage change of >21.5% NLR.

Univariate analysis demonstrated that carcino-embryonic antigen (CEA) prior to treatment, tumor differentiation, chemotherapy regimens and the percentage change in NLR were associated with pCR (Table III). A total of 45% of patients with a percentage change of ≤21.5% NLR achieved pCR compared with 23% of patients with a percentage change of >21.5% NLR (P=0.001; Fig. 3). Multivariate analysis included all variables in the univariate analysis, including sex, CEA prior to treatment, tumor scope, tumor differentiation, chemotherapy regimens and the percentage change in NLR (P<0.1). However, only the percentage change in NLR (P=0.006; OR=0.413; 95% CI=0.22–0.773) and chemotherapy regimens (P=0.042; OR=2.257; 95% CI=1.031–4.942) were significant following multivariate analysis. Sex (P=0.345), CEA prior to treatment (P=0.052), tumor differentiation (P=0.173) and tumor circumference (P=0.294) were not significant. Thus, the percentage change in NLR and chemotherapy regimens were significant predictors of pCR.

Table III.

Univariate and multivariate analysis in the training cohort.

Table III.

Univariate and multivariate analysis in the training cohort.

UnivariateMultivariate


VariableOR value (95% CI)P-valueOR value (95% CI)P-value
Age (≤65 vs. >65 years)1.14 (0.62–2.11)0.668
Sex (male vs. female)0.47 (0.21–1.08)0.0701.38 (0.71–2.68)0.345
CEA prior to treatment (≤5 vs. >5 µg/l)0.44 (0.24–0.82)0.0090.53 (0.27–1.01)0.052
Clinical T stage (T2 vs. >T3-4)1.08 (0.55–2.13)0.817
Clinical N stage (N0 vs. N1-2)0.97 (0.43–2.17)0.955
Tumor size (≤5 vs. >5 cm)1.42 (0.74–2.72)0.628
Tumor circumference (≤50 vs. >50%)0.59 (0.33–1.05)0.0730.72 (0.39–1.33)0.294
Mesorectal fascia (negative vs. positive)1.07 (0.59–1.94)0.832
Distance from anal verge (≤5 vs. >5 cm)0.69 (0.39–1.23)0.204
Tumor differentiation (low vs. medium, high)0.36 (0.17–0.90)0.0230.51 (0.19–1.34)0.173
Operation interval of radiotherapy (≤7 vs. >7 weeks)1.36 (0.76–2.44)0.301
Chemotherapy regimens (with oxaliplatin vs. without oxaliplatin)3.04 (1.44–6.41)0.0032.26 (1.03–4.94)0.042
Chemotherapy courses (≤4 vs. >4)1.91 (0.74–4.91)0.174
% change in NLR (≤21.5 vs. >21.5)0.36 (0.20–0.67)0.0010.41 (0.22–0.77)0.006

[i] CEA, carcino-embryonic antigen; T, tumor; N, lymph node; NLR, neutrophil-to-lymphocyte ratio; OR, odds ratio; CI, confidence interval.

Analysis for pCR in the validation cohort

Percentage change of 21.5% NLR was considered to be optimal to predict pCR events in the training cohort (Fig. 2). To verify the association between the percentage change in NLR and pCR, univariate and multivariate analysis for pCR were performed for the validation cohort (Table IV). Univariate analysis demonstrated that tumor differentiation, chemotherapy regimens and the percentage change in NLR were associated with pCR. However, only the percentage change in NLR (P=0.03; OR=0.337; 95% CI=0.126–0.9) was significant following multivariate analysis. In summary, the results verified that the percentage change in NLR was a significant predictor of pCR.

Table IV.

Univariate and multivariate analysis in the validation cohort.

Table IV.

Univariate and multivariate analysis in the validation cohort.

UnivariateMultivariate


VariableOR value (95% CI)P-valueOR value (95% CI)P-value
Age (≤65 vs. >65 years)1.80 (0.58–5.58)0.304
Sex (male vs. female)1.03 (0.39–2.73)0.951
CEA prior to treatment (≤5 vs. >5 µg/l)1.64 (0.66–4.10)0.286
Clinical T stage (T2 vs. >T3-4)1.10 (0.36–3.23)0.862
Clinical N stage (N0 vs. N1-2)1.75 (0.46–6.72)0.411
Tumor size (≤5 vs. >5 cm)0.80 (0.31–2.10)0.650
Tumor circumference (≤50 vs. >50%)0.51 (0.20–1.26)0.140
Mesorectal fascia (negative vs. positive)1.24 (0.48–3.21)0.665
Distance from anal verge (≤5 vs. >5 cm)0.84 (0.33–2.16)0.722
Tumor differentiation (low vs. medium, high)0.33 (0.08–1.45)0.0230.32 (0.07–1.55)0.157
Operation interval of radiotherapy (≤7 vs. >7 weeks)1.97 (0.70–5.54)0.194
Chemotherapy regimens (with oxaliplatin vs. without oxaliplatin)3.06 (0.95–9.87)0.0542.18 (0.64–7.47)0.213
Chemotherapy course (≤4 vs. >4 courses)1.76 (0.53–5.84)0.348
Percentage change in NLR (≤21.5 vs. >21.5%)0.34 (0.13–0.85)0.0190.34 (0.13–0.90)0.030

[i] CEA, carcino-embryonic antigen; T, tumor; N, lymph node; NLR, neutrophil-to-lymphocyte ratio; OR, odds ratio; CI, confidence interval.

Discussion

Systemic inflammatory responses have become a focus of interest for physicians, and cancer-related inflammatory responses have been recognized as a ‘hallmark’ of cancer development and progression (26). PLR and NLR are important indicators of systemic inflammatory responses (27,28) and the increase in these indicators has been confirmed as adverse factors for the prognosis of multiple malignant tumors, including colon cancer and rectal cancer (29,30). However, the association between systemic inflammatory responses and tumor regression following nCRT in patients with LARC remains unclear. In the current study, pre- and post-nCRT NLR and PLR, and changes in these indices from pre-nCRT to post-nCRT were investigated. Through logistic regression analysis, the results demonstrated that the percentage change in NLR was associated with pCR. These findings were validated by the validation cohort. To the best of our knowledge, the current study is the first to assess the predictive impact of NLR change on tumor treatment outcomes of nCRT in patients with LARC. The results demonstrated that the percentage change in NLR from pre-nCRT to post-nCRT could be used to identify patients achieving pCR following nCRT.

Previous studies have focused on the predictive value of baseline systemic inflammatory responses. Dudani et al (31) reviewed 1,527 patients with rectal cancer receiving nCRT and surgery, and revealed that NLR and PLR were not predictors for disease-free survival or overall survival, and could not predict pCR. Additionally, Shen et al (29) reported that there was no significant association between tumor response and NLR to nCRT. It has previously been reported that baseline systemic inflammatory responses could not predict tumor responses in colorectal cancer (32,33). In the present study, there was no significant association between pCR and NLR or PLR during nCRT.

Furthermore, the results also revealed that adding oxaliplatin to the chemotherapy regimens improved the rate of pCR. Currently, it is controversial whether combining Oxaliplatin with nCRT could improve prognosis and the rate of pCR. The results from the FOWARC study demonstrated that the application of oxaliplatin to nCRT for the treatment of middle and lower rectal cancer exhibited higher rates of pCR (34). Allegra et al (35) compared the rates of pCR in patients receiving neoadjuvant chemoradiotherapy with or without oxaliplatin, and the results did not indicate any significant differences (17.8 vs. 19.5%; P=0.42), which were inconsistent with the results obtained in the current study. This may be due to the higher dose used in the current study and the FOWARC study compared with that used in other studies (85 vs. 50–60 mg/m2) (34,35).

In numerous studies involving rectal cancer, CEA levels were investigated as potential predictors of rectal cancer. Moureau-Zabotto et al (36) demonstrated that a pre-nCRT serum CEA level of <5 ng/ml was significantly associated with pCR and tumor downstaging (36). However, other studies did not support this conclusion (37). In the current study, a pre-nCRT serum CEA level of ≤5 ng/ml was significantly associated with pCR according to univariate analysis; however, the results of multivariate analysis (P=0.052) were not significant. This result may be due to the small simple size used in the current study.

The present study had several limitations. Since data was obtained from a single center, the results could not be validated with those from another institute. Furthermore, the retrospective observational design of the current study may cause bias. Further prospective studies are required to validate the results of the present study. The results demonstrated an association between the percentage change in NLR and responsiveness to nCRT among patients with rectal cancer. However, the results failed to determine the cause of this association. Furthermore, a reduction in circulating immunocytes may be due to cytotoxic neoadjuvant chemotherapy. However, neoadjuvant radiation and chemotherapy have been reported to release neoantigens by killing tumor cells, and the immune reaction may cause an increase in circulating immunocytes (38). However, the ratios of different immunocytes as an independent prognostic factor, or parameters associated to therapeutic activity were not examined. Therefore, additional prognostic data is required.

In conclusion, the results of the current study investigated the pre- and post-nCRT systemic inflammatory indices and changes in these indices from pre-nCRT to post-nCRT. The association between the percentage change in NLR and responsiveness to nCRT among patients with rectal cancer was determined, and the results demonstrated that this association could identify patients who achieved pCR following neoadjuvant chemoradiotherapy. These results may provide a novel strategy for colorectal cancer treatment.

Acknowledgements

Not applicable.

Funding

The present study was supported by the Fundamental Research Funds for the Central Universities (grant no. 16ykjc25), the Sun Yat-Sen University Clinical Research 5010 Program (grant no. 2016005), the National Health and Medical Research Council Grant (grant no. 1158402) and the Natural Science Foundation of Guangdong Province (grant no. 2018A030313621).

Availability of data and materials

The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

Authors' contributions

SCL, LW, JD and LK designed the study. SLL and LH were responsible for data collection. ZL and SCL analyzed data. SLL, LH, JD, LW and LK drafted the manuscript. SCL, JD and LW revised the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate

The study protocol was reviewed and approved by the Institutional Review Board of the Sixth Affiliated Hospital, Sun Yat-sen University, China. The present study was carried out in accordance with the recommendations of the Declaration of Helsinki for biomedical research involving human patients. Written informed consent was obtained from patients prior to enrollment.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Glossary

Abbreviations

Abbreviations:

nCRT

neoadjuvant chemoradiotherapy

LARC

locally advanced rectal cancer

NLR

neutrophil-to-lymphocyte ratio

PLR

platelet-to-lymphocyte ratio

pCR

pathological complete response

TRG

tumor regression grade

CEA

carcino-embryonic antigen

References

1 

Brenner H, Kloor M and Pox CP: Colorectal cancer. Lancet. 383:1490–1502. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Benson AB, Venook AP, Al-Hawary MM, Cederquist L, Chen YJ, Ciombor KK, Cohen S, Cooper HS, Deming D, Engstrom PF, et al: Rectal cancer, version 2.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 16:874–901. 2018. View Article : Google Scholar : PubMed/NCBI

3 

Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, et al: Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: Initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol. 13:679–687. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Bryant CL, Lunniss PJ, Knowles CH, Thaha MA and Chan CL: Anterior resection syndrome. Lancet Oncol. 13:e403–e408. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Fazio VW, Zutshi M, Remzi FH, Parc Y, Ruppert R, Fürst A, Celebrezze J Jr, Galanduik S, Orangio G, Hyman N, et al: A randomized multicenter trial to compare long-term functional outcome, quality of life, and complications of surgical procedures for low rectal cancers. Ann Surg. 246:481–490. 2007. View Article : Google Scholar : PubMed/NCBI

6 

Paun BC, Cassie S, MacLean AR, Dixon E and Buie WD: Postoperative complications following surgery for rectal cancer. Ann Surg. 251:807–818. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Nahas SC, Rizkallah Nahas CS, Sparapan Marques CF, Ribeiro U Jr, Cotti GC, Imperiale AR, Capareli FC, Chih Chen AT, Hoff PM and Cecconello I: Pathologic complete response in rectal cancer: Can we detect it? Lessons learned from a proposed randomized trial of watch-and-wait treatment of rectal cancer. Dis Colon Rectum. 59:255–263. 2016. View Article : Google Scholar : PubMed/NCBI

8 

Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U Jr, Silva e Sousa AH Jr, Campos FG, Kiss DR and Gama-Rodrigues J: Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: Long-term results. Ann Surg. 240:711–717; discussion 717–718. 2004.PubMed/NCBI

9 

van der Valk MJM, Hilling DE, Bastiaannet E, Meershoek-Klein Kranenbarg E, Beets GL, Figueiredo NL, Habr-Gama A, Perez RO, Renehan AG and van de Velde CJH; IWWD Consortium, : Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): An international multicentre registry study. Lancet. 391:2537–2545. 2018. View Article : Google Scholar : PubMed/NCBI

10 

Habr-Gama A, São Julião GP, Fernandez LM, Vailati BB, Andrade A, Araújo SEA, Gama-Rodrigues J and Perez RO: Achieving a complete clinical response After neoadjuvant chemoradiation that does not require surgical resection: It may take longer than you think! Dis Colon Rectum. 62:802–808. 2019. View Article : Google Scholar : PubMed/NCBI

11 

Yeom SS, Lee SY, Kim CH, Kim YJ, Nam TK and Kim HR: The outcome of non-operative treatment for rectal cancer patients who had been cCR after neoadjuvant chemoradiotherapy. Asian J Surg. 42:2019. View Article : Google Scholar : PubMed/NCBI

12 

Renehan AG, Malcomson L, Emsley R, Scott N and O'Dwyer ST; OnCoRe project investigators, : Watch-and-wait versus surgical resection for patients with rectal cancer-Authors' reply. Lancet Oncol. 17:e134–e135. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Kong JC, Guerra GR, Warrier SK, Ramsay RG and Heriot AG: Outcome and salvage surgery following ‘watch and wait’ for rectal cancer after neoadjuvant therapy: A systematic review. Dis Colon Rectum. 60:335–345. 2017. View Article : Google Scholar : PubMed/NCBI

14 

Malietzis G, Giacometti M, Askari A, Nachiappan S, Kennedy RH, Faiz OD, Aziz O and Jenkins JT: A preoperative neutrophil to lymphocyte ratio of 3 predicts disease-free survival after curative elective colorectal cancer surgery. Ann Surg. 260:287–292. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Lee DY, Hong SW, Chang YG, Lee WY and Lee B: Clinical significance of preoperative inflammatory parameters in gastric cancer patients. J Gastric Cancer. 13:111–116. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Stotz M, Gerger A, Eisner F, Szkandera J, Loibner H, Ress AL, Kornprat P, AlZoughbi W, Seggewies FS, Lackner C, et al: Increased neutrophil-lymphocyte ratio is a poor prognostic factor in patients with primary operable and inoperable pancreatic cancer. Br J Cancer. 109:416–421. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Pichler M, Hutterer GC, Stoeckigt C, Chromecki TF, Stojakovic T, Golbeck S, Eberhard K, Gerger A, Mannweiler S, Pummer K and Zigeuner R: Validation of the pre-treatment neutrophil-lymphocyte ratio as a prognostic factor in a large European cohort of renal cell carcinoma patients. Br J Cancer. 108:901–907. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Azab B, Shah N, Radbel J, Tan P, Bhatt V, Vonfrolio S, Habeshy A, Picon A and Bloom S: Pretreatment neutrophil/lymphocyte ratio is superior to platelet/lymphocyte ratio as a predictor of long-term mortality in breast cancer patients. Med Oncol. 30:4322013. View Article : Google Scholar : PubMed/NCBI

19 

Yamada S, Fujii T, Yabusaki N, Murotani K, Iwata N, Kanda M, Tanaka C, Nakayama G, Sugimoto H, Koike M, et al: Clinical implication of inflammation-based prognostic score in pancreatic cancer: Glasgow prognostic score is the most reliable parameter. Medicine (Baltimore). 95:e35822016. View Article : Google Scholar : PubMed/NCBI

20 

Li MX, Liu XM, Zhang XF, Zhang JF, Wang WL, Zhu Y, Dong J, Cheng JW, Liu ZW, Ma L and Lv Y: Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: A systematic review and meta-analysis. Int J Cancer. 134:2403–2413. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Roxburgh CS, Salmond JM, Horgan PG, Oien KA and McMillan DC: The relationship between the local and systemic inflammatory responses and survival in patients undergoing curative surgery for colon and rectal cancers. J Gastrointest Surg. 13:2011–2019. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Heo J, Oh YT, Noh OK, Chun M, Park JE and Cho SR: Nodal tumor response according to the count of peripheral blood lymphocyte subpopulations during preoperative chemoradiotherapy in locally advanced rectal cancer. Radiat Oncol J. 34:305–312. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Lee IH, Hwang S, Lee SJ, Kang BW, Baek D, Kim HJ, Park SY, Park JS, Choi GS, Kim JC, et al: Systemic inflammatory response after preoperative chemoradiotherapy can affect oncologic outcomes in locally advanced rectal cancer. Anticancer Res. 37:1459–1465. 2017. View Article : Google Scholar : PubMed/NCBI

24 

Laird BJ, Fallon M, Hjermstad MJ, Tuck S, Kaasa S, Klepstad P and McMillan DC: Quality of life in patients with advanced cancer: Differential association with performance status and systemic inflammatory response. J Clin Oncol. 34:2769–2775. 2016. View Article : Google Scholar : PubMed/NCBI

25 

Tong GJ, Zhang GY, Liu J, Zheng ZZ, Chen Y, Niu PP and Xu X: Comparison of the eighth version of the American Joint Committee on Cancer manual to the seventh version for colorectal cancer: A retrospective review of our data. World J Clin Oncol. 9:148–161. 2018. View Article : Google Scholar : PubMed/NCBI

26 

Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Gomez D, Morris-Stiff G, Toogood GJ, Lodge JP and Prasad KR: Impact of systemic inflammation on outcome following resection for intrahepatic cholangiocarcinoma. J Surg Oncol. 97:513–518. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Ku JH, Kang M, Kim HS, Jeong CW, Kwak C and Kim HH: The prognostic value of pretreatment of systemic inflammatory responses in patients with urothelial carcinoma undergoing radical cystectomy. Br J Cancer. 112:461–467. 2015. View Article : Google Scholar : PubMed/NCBI

29 

Shen L, Zhang H, Liang L, Li G, Fan M, Wu Y, Zhu J and Zhang Z: Baseline neutrophil-lymphocyte ratio (≥2.8) as a prognostic factor for patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation. Radiat Oncol. 9:2952014. View Article : Google Scholar : PubMed/NCBI

30 

Braun LH, Baumann D, Zwirner K, Eipper E, Hauth F, Peter A, Zips D and Gani C: Neutrophil-to-lymphocyte ratio in rectal cancer-novel biomarker of tumor immunogenicity during radiotherapy or confounding variable? Int J Mol Sci. 20:24482019. View Article : Google Scholar

31 

Dudani S, Marginean H, Tang PA, Monzon JG, Raissouni S, Asmis TR, Goodwin RA, Gotfrit J, Cheung WY and Vickers MM: Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictive and prognostic markers in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation. BMC Cancer. 19:6642019. View Article : Google Scholar : PubMed/NCBI

32 

Picardo SL, Teo M, Jalil KIA, Naqvi SY, Morris PG, Breathnach OS, Grogan W, Leonard GD and Hennessy B: Correlation between platelet/lymphocyte ratio, neutrophil/lymphocyte ratio and response to neoadjuvant chemoradiation therapy in rectal cancer. J Clin Oncol. 34:e151402016. View Article : Google Scholar

33 

Shin US, You YN, Price BA, Rodriguez-Bigas MA, Skibber JM, Maru DM, Taggart MW, Kopetz S, Eng C, Minsky BD, et al: Is the neutrophil-lymphocyte ratio (NLR) a predictive and prognostic factor in rectal cancer patients treated with neoadjuvant chemoradiation (nCRT)? J Clin Oncol. 34:36052016. View Article : Google Scholar : PubMed/NCBI

34 

Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, et al: Modified FOLFOX6 with or without radiation versus fluorouracil and leucovorin with radiation in neoadjuvant treatment of locally advanced rectal cancer: Initial results of the Chinese FOWARC multicenter, open-label, randomized three-arm phase III trial. J Clin Oncol. 34:3300–3307. 2016. View Article : Google Scholar : PubMed/NCBI

35 

Allegra CJ, Yothers G, O'Connell MJ, Beart RW, Wozniak TF, Pitot HC, Shields AF, Landry JC, Ryan DP, Arora A, et al: Neoadjuvant 5-FU or capecitabine plus radiation with or without oxaliplatin in rectal cancer patients: A phase III randomized clinical trial. J Natl Cancer Inst. 107:djv2482015. View Article : Google Scholar : PubMed/NCBI

36 

Moureau-Zabotto L, Farnault B, de Chaisemartin C, Esterni B, Lelong B, Viret F, Giovannini M, Monges G, Delpero JR, Bories E, et al: Predictive factors of tumor response after neoadjuvant chemoradiation for locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 80:483–491. 2011. View Article : Google Scholar : PubMed/NCBI

37 

Kalady MF, de Campos-Lobato LF, Stocchi L, Geisler DP, Dietz D, Lavery IC and Fazio VW: Predictive factors of pathologic complete response after neoadjuvant chemoradiation for rectal cancer. Ann Surg. 250:582–589. 2009.PubMed/NCBI

38 

Burnette B, Fu YX and Weichselbaum RR: The confluence of radiotherapy and immunotherapy. Front Oncol. 2:1432012. View Article : Google Scholar : PubMed/NCBI

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September-2020
Volume 20 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Copy and paste a formatted citation
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Spandidos Publications style
Lai S, Huang L, Luo S, Liu Z, Dong J, Wang L and Kang L: Systemic inflammatory indices predict tumor response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Oncol Lett 20: 2763-2770, 2020.
APA
Lai, S., Huang, L., Luo, S., Liu, Z., Dong, J., Wang, L., & Kang, L. (2020). Systemic inflammatory indices predict tumor response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Oncology Letters, 20, 2763-2770. https://doi.org/10.3892/ol.2020.11812
MLA
Lai, S., Huang, L., Luo, S., Liu, Z., Dong, J., Wang, L., Kang, L."Systemic inflammatory indices predict tumor response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer". Oncology Letters 20.3 (2020): 2763-2770.
Chicago
Lai, S., Huang, L., Luo, S., Liu, Z., Dong, J., Wang, L., Kang, L."Systemic inflammatory indices predict tumor response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer". Oncology Letters 20, no. 3 (2020): 2763-2770. https://doi.org/10.3892/ol.2020.11812