Introduction: The standard therapy for locally advanced rectal cancer (LARC) is based on neoadjuvant chemoradiotherapy (nCRT) with fluoropyrimidines. There are different biomarkers used as prognostic factors in these tumors. Some studies advocate the use of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic factors in this clinical scenario. The aim of the study was to evaluate NLR and PLR as prognostic factors of disease-free survival (DFS) and overall survival (OS) and as predictive factors of pathologic complete response (pCR) using Ryan tumor regression scoring system on surgical specimens, in patients with locally advanced rectal adenocarcinoma who received nCRT and radical surgery. Methods: We retrospectively evaluated patients with locally advanced rectal adenocarcinoma (T3-T4, N1-N3, M0 according to the TNM classification, AJCC 8th edition) who received nCRT based on fluoropyrimidines and radical surgery. Complete blood cell count before nCRT was obtained to calculate NLR and PLR. We made subgroups of patients according to NLR and PLR. We obtained the cut-off point for these ratios based on receiver operating characteristic analysis. We analyzed OS and DFS using the Kaplan-Meier method and Cox proportional hazard models. The relationships between NLR/PLR and pCR, along with other clinical-pathological characteristics, were evaluated by Pearson’s χ2 or Fisher’s exact test as appropriate. Multivariate analyses were performed using Cox proportional hazard regression models. Results: Between February 2012 and February 2017, 100 consecutive patients were treated according to the reported schedules. Median age was 76 years (68–83). All patients received radiotherapy up to 50.4 Gy and 5-FU-based chemotherapy. 100% completed nCRT and surgery, 38% had elevated basal NLR (cut-off >1.95), and 50% had elevated basal PLR (cut-off >133). After a median follow-up of 72 months (55–88), a lower DFS was obtained in the high NLR subgroup (log-rank, Mantel-Cox 5.165, p = 0.023) and in the high PLR subgroup (log-rank, Mantel-Cox 13.971, p = 0.001). Multivariate analysis showed that PLR (p = 0.006) was a strong significant predictor of DFS. A lower OS was observed in the high NLR and PLR subgroup without significant differences (log-rank, Mantel-Cox 1.245, p = 0.265; 0.578, p = 0.447). No significant differences were obtained in any of the subgroup analysis regarding pCR rates. Conclusion: In light of our results, both NLR and PLR could be considered prognostic factors for DFS in patients with LARC that receive treatment with nCRT followed by surgery.

1.
Sung
H
,
Ferlay
J
,
Siegel
RL
,
Laversanne
M
,
Soerjomataram
I
,
Jemal
A
.
Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries
.
CA Cancer J Clin
.
2021
;
71
(
3
):
209
49
.
2.
Wasserberg
N
.
Interval to surgery after neoadjuvant treatment for colorectal cancer
.
World J Gastroenterol
.
2014
;
20
(
15
):
4256
62
.
3.
Sauer
R
,
Becker
H
,
Hohenberger
W
,
Rödel
C
,
Wittekind
C
,
Fietkau
R
.
Preoperative versus postoperative chemoradiotherapy for rectal cancer
.
N Engl J Med
.
2004
;
351
(
17
):
1731
40
.
4.
Bosset
JF
,
Collette
L
,
Calais
G
,
Mineur
L
,
Maingon
P
,
Radosevic-Jelic
L
.
Chemotherapy with preoperative radiotherapy in rectal cancer
.
N Engl J Med
.
2006
;
355
(
11
):
1114
23
.
5.
Glynne-Jones
R
,
Wyrwicz
L
,
Tiret
E
,
Brown
G
,
Rödel
C
,
Cervantes
A
.
Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
.
Ann Oncol
.
2017
;
28
(
4
):
22
40
.
6.
NCCN guidelines panel
.
Rectal Cancer v
.
2021 Dec
1
2020
.
7.
Roh
MS
,
Colangelo
LH
,
O’Connell
MJ
,
Yothers
G
,
Deutsch
M
,
Allegra
CJ
.
Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: nsabp R-03
.
J Clin Oncol
.
2009
;
27
(
31
):
5124
30
.
8.
Sauer
R
,
Liersch
T
,
Merkel
S
,
Fietkau
R
,
Hohenberger
W
,
Hess
C
.
Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years
.
J Clin Oncol
.
2012
;
30
(
16
):
1926
33
.
9.
Martin
ST
,
Heneghan
HM
,
Winter
DC
.
Systematic review and meta-Analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer
.
Br J Surg
.
2012
;
99
(
7
):
918
28
.
10.
Fokas
E
,
Liersch
T
,
Fietkau
R
,
Hohenberger
W
,
Beissbarth
T
,
Hess
C
.
Tumor regression grading after preoperative chemoradiotherapy for locally advanced rectal carcinoma revisited: updated results of the CAO/ARO/AIO-94 trial
.
J Clin Oncol
.
2014
;
32
(
15
):
1554
62
.
11.
Wu
Q
,
Hu
T
,
Zheng
E
,
Deng
X
,
Wang
Z
.
Prognostic role of the lymphocyte-to-monocyte ratio in colorectal cancer
.
Medicine
.
2017
;
96
(
22
):
e7051
5
.
12.
Ke
TM
,
Lin
LC
,
Huang
CC
,
Chien
YW
,
Ting
WC
,
Yang
CC
.
High neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio predict poor survival in rectal cancer patients receiving neoadjuvant concurrent chemoradiotherapy
.
Medicine
.
2020
;
99
(
17
):
e19877
.
13.
Dudani
S
,
Marginean
H
,
Tang
PA
,
Monzon
JG
,
Raissouni
S
,
Asmis
TR
.
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
.
2019
;
19
(
1
):
664
.
14.
Li
A
,
He
K
,
Guo
D
,
Liu
C
,
Wang
D
,
Mu
X
.
Pretreatment blood biomarkers predict pathologic responses to neo-CRT in patients with locally advanced rectal cancer
.
Future Oncol
.
2019
;
15
(
28
):
3233
42
.
15.
Zhang
Y
,
Liu
X
,
Xu
M
,
Chen
K
,
Li
S
,
Guan
G
.
Prognostic value of pretreatment systemic inflammatory markers in patients with locally advanced rectal cancer following neoadjuvant chemoradiotherapy
.
Sci Rep
.
2020 May 15
10
1
8017
.
16.
Myerson
RJ
,
Garofalo
MC
,
El Naqa
I
,
Abrams
RA
,
Apte
A
,
Bosch
WR
.
Elective clinical target volumes for conformal therapy in anorectal cancer: a radiation therapy oncology group consensus panel contouring atlas
.
Int J Radiat Oncol Biol Phys
.
2009
;
74
(
3
):
824
30
.
17.
Ryan
R
,
Gibbons
D
,
Hyland
JMP
,
Treanor
D
,
White
A
,
Mulcahy
HE
.
Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer
.
Histopathology
.
2005
;
47
(
2
):
141
6
.
18.
Grivennikov
SI
,
Greten
FR
,
Karin
M
.
Immunity, inflammation, and cancer
.
Cell
.
2010
;
140
(
6
):
883
99
.
19.
Balkwill
F
,
Mantovani
A
.
Inflammation and cancer: back to Virchow
.
Lancet
.
2001
;
357
(
9255
):
539
45
.
20.
Shen
L
,
Zhang
H
,
Liang
L
,
Li
G
,
Fan
M
,
Wu
Y
.
Baseline neutrophil-lymphocyte ratio (≥2.8) as a prognostic factor for patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation
.
Radiat Oncol
.
2014
;
9
:
295
.
21.
Dong
YW
,
Shi
YQ
,
He
LW
,
Su
PZ
.
Prognostic significance of neutrophil-to-lymphocyte ratio in rectal cancer: a meta-analysis
.
Onco Targets Ther
.
2016
;
9
:
3127
34
.
22.
Portale
G
,
Cavallin
F
,
Valdegamberi
A
,
Frigo
F
,
Fiscon
V
.
Platelet-to-Lymphocyte ratio and neutrophil-to-lymphocyte ratio are not prognostic biomarkers in rectal cancer patients with curative resection
.
J Gastrointest Surg
.
2018
;
22
(
9
):
1611
8
.
23.
Cha
YJ
,
Park
EJ
,
Baik
SH
,
Lee
KY
,
Kang
J
.
Prognostic impact of persistent lower neutrophil-to-lymphocyte ratio during preoperative chemoradiotherapy in locally advanced rectal cancer patients: a propensity score matching analysis
.
PLoS One
.
2019
;
14
(
3
):
e0214415
18
.
24.
Kitayama
J
,
Yasuda
K
,
Kawai
K
,
Sunami
E
,
Nagawa
H
.
Circulating lymphocyte number has a positive association with tumor response in neoadjuvant chemoradiotherapy for ad- vanced rectal cancer
.
Radiat Oncol
.
2010
;
5
:
47
.
25.
Kim
TG
,
Park
W
,
Kim
H
,
Choi
DH
,
Park
HC
,
Kim
SH
.
Baseline neutrophil–lymphocyte ratio and platelet–lymphocyte ratio in rectal cancer patients following neoadjuvant chemoradiotherapy
.
Tumori
.
2019
;
201105
(
5
):
434
40
.
26.
Azab
B
,
Jaglall
N
,
Atallah
JP
,
Lamet
A
,
Raja-Surya
V
,
Farah
B
.
Neutrophil-lymphocyte ratio as a pre- dictor of adverse outcomes of acute pancreatitis
.
Pancreatology
.
2011
;
11
(
4
):
445
52
.
27.
Cienfuegos
JA
,
Rotellar
F
,
Baixauli
J
,
Beorlegui
C
,
Sola
JJ
,
Arbea
L
.
Impact of perineural and lymphovascular invasion on oncological outcomes in rectal cancer treated with neoadjuvant chemoradiotherapy and surgery
.
Ann Surg Oncol
.
2015
;
22
(
3
):
916
23
.
28.
Cercek
A
,
Roxburgh
CSD
,
Strombom
P
,
Smith
JJ
,
Temple
LKF
,
Nash
GM
.
Adoption of Total neoadjuvant therapy for locally advanced rectal Cancer
.
JAMA Oncol
.
2018
;
4
(
6
):
e180071
.
29.
Kasi
A
,
Abbasi
S
,
Handa
S
,
Al-Rajabi
R
,
Saeed
A
,
Baranda
J
.
Total neoadjuvant therapy vs standard therapy in locally advanced rectal cancer: a systematic review and meta-analysis
.
JAMA Netw Open
.
2020
;
3
(
12
):
e2030097
.
30.
Garcia-Aguilar
J
,
Chow
OS
,
Smith
DD
,
Marcet
JE
,
Cataldo
PA
,
Varma
MG
.
Timing of Rectal Cancer Response to Chemoradiation Consortium. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial
.
HHS Public Access
.
2016
;
16
(
8
):
957
66
.
31.
Bahadoer
RR
,
Dijkstra
EA
,
van Etten
B
,
Marijnen
CAM
,
Putter
H
,
Kranenbarg
EMK
.
Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial
.
Lancet Oncol
.
2021
;
22
(
1
):
29
42
.
32.
Dossa
F
,
Chesney
TR
,
Acuna
SA
,
Baxter
NN
.
A watch-and-wait approach forlocally advanced rectalcancer after a clinical complete response following neoadjuvant chemoradiation: a systematic review and meta-analysis
.
Lancet Gastroenterol Hepatol
.
2017
;
2
(
7
):
501
13
.
33.
Appelt
AL
,
Ploen
J
,
Harling
H
,
Jensen
FS
,
Jensen
LH
,
Jørgensen
JCR
.
High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study
.
Lancet Oncol
.
2015
;
16
(
8
):
919
27
.
34.
Renehan
AG
,
Malcomson
L
,
Emsley
R
,
Gollins
S
,
Maw
A
,
Myint
AS
.
Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis
.
Lancet Oncol
.
2016
;
17
(
2
):
174
83
.
35.
Smith
JJ
,
Strombom
P
,
Chow
OS
,
Roxburgh
CS
,
Lynn
P
,
Eaton
A
.
Assessment of a watch-and-wait strategy for rectal cancer in patients with a complete response after neoadjuvant therapy
.
JAMA Oncol
.
2019
;
5
(
4
):
e185896
.
36.
You
YN
,
Hardiman
KM
,
Bafford
A
,
Poylin
V
,
Francone
TD
,
Davis
K
.
The American society of colon and rectal surgeons clinical practice guidelines for the management of rectal cancer
.
Dis Colon Rectum
.
2020
;
63
(
9
):
1191
222
.
37.
Pauli
C
,
Hopkins
BD
,
Prandi
D
,
Shaw
R
,
Fedrizzi
T
,
Sboner
A
.
Personalized in vitro and in vivo cancer models to guide precision medicine
.
Cancer Discov
.
2017
;
7
(
5
):
462
77
.
38.
Eggermont
A
,
Geoerger
B
,
Curigliano
G
.
Precision cancer medicine: large studies indicate steady progress
.
Cancer Discov
.
2021
;
11
(
11
):
2677
8
.
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