Retrospective Clinical Research Report

Journal of International Medical Research

50(6) 1–12
The prognostic value of ! The Author(s) 2022
Article reuse guidelines:
the advanced lung cancer sagepub.com/journals-permissions
DOI: 10.1177/03000605221109382
inflammation index (ALI) for journals.sagepub.com/home/imr

patients with neuroblastoma

Can Qi1,2, Yun Zhou2, Zhonghui Hu3,

Huizhong Niu2, Fang Yue2, Huibo An4,
Zhiguo Chen2, Ping Wang2, Le Wang5 and
Guochen Duan1,2,5

Abstract
Objective: The advanced lung cancer inflammation index (ALI) can predict the survival of
patients with lung cancer and other malignancies. However, the prognostic significance of ALI
in neuroblastoma has not been reported. This study aimed to evaluate the correlation between
ALI and neuroblastoma patient prognosis.
Methods: We retrospectively analyzed the data of 72 neuroblastoma patients treated between
January 2014 and August 2020. ALI calculation: Body mass index (BMI)
serum albumin (ALB)/
neutrophil-to-lymphocyte ratio (NLR). The optimal cutoff points of prognostic biomarkers were
determined by generating receiver operating characteristic (ROC) curves. According to the
cutoff value, the patients were categorized into low or high ALI groups. The chi-square test
was used to compare clinical parameters between the two groups. Potential prognostic factors
associated with overall survival (OS) were assessed using Kaplan–Meier and Cox regression
analyses.
Results: The optimal cutoff value of ALI was 49.17. The low ALI group showed more severe
clinical characteristics and poorer survival rates. Univariate and multivariate Cox analyses
suggested that ALI and the International Neuroblastoma Staging System (INSS) stage were
independent prognostic factors for neuroblastoma patients.

4
Department of Pathology, Children’s Hospital of Hebei
Province, Shijiazhuang, People’s Republic of China
5
1
Study Office of Pediatric and Thoracic Surgery, Hebei Children’s Disease and Health Research Center of Hebei
Medical University, Shijiazhuang, People’s Republic of Province, Shijiazhuang, People’s Republic of China
China Corresponding author:
2
Department of Pediatric Surgery, Children’s Hospital of Guochen Duan, Children’s Hospital of Hebei Province,
Hebei Province, Shijiazhuang, People’s Republic of China No. 133 Jianhua South Street, Yuhua District, Shijiazhuang
3
Department of Thoracic Surgery, Hebei General 050000, People’s Republic of China.
Hospital, Shijiazhuang, People’s Republic of China Email: [email protected]

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2 Journal of International Medical Research

Conclusions: Low ALI is associated with poor prognosis in neuroblastoma patients. ALI may be
an independent prognostic biomarker for neuroblastoma.

Keywords
Neuroblastoma, advanced lung cancer inflammation index, prognosis, overall survival, biomarker,
cancer, inflammation
Date received: 20 January 2022; accepted: 6 June 2022

Introduction platelet-to-lymphocyte ratio (PLR), and

lymphocyte-to-monocyte ratio (LMR),
Neuroblastoma, the most prevalent extra-
which have been identified as potential prog-
cranial solid tumor in children, mostly
nostic biomarkers for cancer patients.9,10
occurs in the mediastinum, abdomen, and
The advanced lung cancer inflammation
pelvic cavity.1–3 Neuroblastoma accounts
index (ALI), which is based on the NLR,
for 15% of cancer deaths in children, and
body mass index (BMI), and serum albumin
has complex heterogeneity and a broad
(ALB), was designed by Jafri et al. to inves-
spectrum of clinical behavior.4 Although
tigate the prognosis of advanced non-small
advanced therapies, including surgery, cell lung cancer patients.11 ALI has recently
radiotherapy, chemotherapy, myeloablative been reported to be correlated with the prog-
consolidation therapy with stem cell nosis of many other malignancies such as
rescue or transplantation, and immunother- melanoma, esophageal squamous carcino-
apy, have been utilized to treat this ma, colorectal cancer, and head and neck
disease, many patients still have poor prog- squamous cell carcinoma.12–15 However,
noses.5 Currently, conventional prognostic the prognostic value of ALI in neuroblasto-
factors such as Myc-N proto-oncogene ma patients has not been reported.
(MYCN) amplification or the International Therefore, our study aimed to evaluate the
Neuroblastoma Staging System (INSS) are association between ALI and neuroblastoma
frequently used to predict the overall survival patient prognosis.
(OS) of neuroblastoma patients. However,
because of the complex pathogenesis and
heterogeneity of neuroblastoma, the prog- Methods
nosis of some patients cannot be accurately
predicted using these factors.2,6
Patients
Multiple previous studies have demon- We retrospectively screened data from
strated that the systemic inflammatory neuroblastoma patients treated between
response (SIR) is closely related to the January 2014 and August 2020 at the
development and progression of malignan- Children’s Hospital of Hebei Province.
cies by altering the tumor microenviron- The inclusion criteria were that the patient
ment.7,8 Furthermore, hematologic markers was pathologically diagnosed with neuro-
from routine blood examinations can suc- blastoma, was 18 years old or younger,
cessfully predict cancer prognosis, including had complete clinical data that could be col-
the neutrophil-to-lymphocyte ratio (NLR), lected, and had pre-treatment laboratory
Qi et al. 3

data available. Patients with complicated Table 1. Calculation formulas of relevant

blood system diseases, immune system dis- biomarkers.
eases, or a long-term history of abnormal Index Formula
routine blood examinations were excluded.
All patients received sequential treatment NLR Neutrophil/lymphocyte
according to the Children’s Oncology PLR Platelet/lymphocyte
LMR Lymphocyte/onocyte
Group (COG) guidelines.6 Basic character-
CAR CRP/ALB
istics were collected, including age, sex, Hs-mGPS 0: CRP 3 mg/L
BMI, pathological type, and INSS. 1: CRP >3 mg/L and albumin
Follow-ups with the patients were requested 35 g/L
every three months for the first three years, 2: CRP >3 mg/L and albumin
then every six months thereafter. The end- <35 g/L
point of follow-up was the patient’s OS, SII (Platelet
neutrophil)/lymphocyte
which was defined as the time from initial ALI BMI (kg/m2)
albumin (g/dL)/NLR
treatment to death from any cause. Follow- NLR, neutrophil to lymphocyte ratio; PLR, platelet to
up data could be obtained via telephone or lymphocyte ratio; LMR, lymphocyte to monocyte ratio;
outpatient service, and the deadline was CAR, C-reactive protein to albumin ratio; ALI, advanced
lung cancer inflammation index; ALB, albumin count; CRP,
August 2021. This study was approved C-reactive protein; BMI, body mass index; Hs-mGPS, high-
by the Ethics Committee of Children’s sensitivity modified Glasgow Prognostic Score; SII, system
Hospital of Hebei Province (Approval No. inflammation index.
2021458) and written informed consent
was obtained from each patient or guard- were categorized into low or high ALI
ian. Our study followed the relevant groups. The chi-square test was used to
EQUATOR Network guidelines.16 compare the clinical parameters between
the two groups. Potential prognostic factors
Laboratory parameters associated with OS were assessed using the
The following laboratory parameters were Kaplan–Meier (KM) and Cox regression
collected: white blood cell count (WBC), analyses. The KM method was used to gen-
red blood cell count (RBC), platelet count erate cumulative cancer-specific survival
(PLT), neutrophil count, lymphocyte count, curves. The differences were calculated
monocyte count (MONO), C-reactive pro- using the log-rank test, and the Cox
tein (CRP), and ALB. The detailed calcula- proportional-hazards model was used to
tion methods of the inflammation-based assess the predictive power of potential
indices are summarized in Table 1. prognostic variables. The hazard ratios
(HRs) are displayed as relative risks with
corresponding 95% confidence intervals
Statistical analyses
(CIs). Statistical significance was set at
Statistical analyses were performed using P < 0.05.
SPSS (version 23.0; IBM Corporation,
Armonk, NY, USA). The optimal cutoff
points for NLR, PLR, LMR, systemic
Results
inflammation index (SII), C-reactive pro- Seventy-two patients were enrolled in the
tein to albumin ratio (CAR), and ALI study, with the exception of four patients
values were determined using receiver lost to follow-up. There were 39 female
operating characteristic (ROC) curves. patients and 33 male patients. Thirty
According to the cutoff value, patients patients were diagnosed under the age of
4 Journal of International Medical Research

18 months and 42 patients were diagnosed analysis demonstrated that INSS and ALI
older than 18 months. Eight patients were were independent prognostic factors for neu-
only treated by surgery. Forty-one patients roblastoma patients (P < 0.05) (Table 5).
were treated by surgery followed by chemo-
therapy. Eighteen patients received treat-
Discussion
ment including preoperative neoadjuvant
chemotherapy, surgery, and postoperative Neuroblastoma is the most common extra-
chemotherapy. Five patients were only cranial malignant pediatric solid tumor
treated by chemotherapy after the ultra- with a high mortality rate.1,2 Because of
sound guided biopsy. The median follow- its complex heterogeneity and rapid clinical
up time was 27 months (range of 4 to 92 progression, the prognosis is often poor.
months). Seventeen patients died during the Traditional pathological prognostic factors,
period. The optimal cutoff points of the such as MYCN amplification and INSS,
NLR, PLR, LMR, SII, CAR, and ALI are recognized standards for assessing
parameters are shown in Table 2 and the prognosis of neuroblastoma cases.3
Figure 1. Baseline data are summarized in However, many children with the same
Table 3. Comparisons of clinicopathologi- INSS reportedly have diverse prognoses.4
cal characteristics and other biomarkers Therefore, new indicators are needed to
between the groups are shown in Table 4. improve the prognostic evaluation of
Our study showed that INSS stage, MYCN neuroblastoma.
amplification, high risk, NLR, PLR, It is widely recognized that SIR is closely
LMR, high-sensitivity modified Glasgow associated with the progression and
Prognostic Score (Hs-mGPS), SII, CAR, prognosis of various malignancies.17
and living status were significantly different Inflammatory cytokines can change the
between the low and high ALI groups tumor microenvironment, which may
(P < 0.05). The survival curves shown in reduce the antitumor immune effects, stim-
Figure 2 revealed that patients with low ulate cell proliferation and migration, and
ALI had significantly poorer survival facilitate angiogenesis. Recent studies have
(P < 0.001). The univariate analysis showed clearly suggested that peripheral immune
that advanced INSS stage, MYCN amplifi- cells, including neutrophils, lymphocytes,
cation, high risk, high NLR, high PLR, low and MONO, may play important roles in
LMR, high Hs-mGPS, high SII, high CAR, regulating inflammatory cytokine secretion
and low ALI were risk factors for poor and are strongly associated with tumorigen-
prognoses. Furthermore, the multivariate esis and progression.17–19 Neutrophils can

Table 2. The optimal cutoff points of the biomarkers.

Project AUC Sensitivity Specificity Cutoff point

NLR 0.798 76.5% 81.8% 1.6

PLR 0.703 52.9% 85.8% 170.52
LMR 0.741 72.7% 76.5% 4.6
SII 0.767 64.7% 80.0% 694.74
CAR 0.814 76.5% 83.6% 0.153
ALI 0.850 76.4% 76.5% 49.17
AUC, area under the curve; NLR, neutrophil to lymphocyte ratio; PLR, platelet to lymphocyte ratio;
LMR, lymphocyte to monocyte ratio; SII, systemic inflammation index; CAR, C-reactive protein to
albumin ratio; ALI, advanced lung cancer inflammation index.
Qi et al. 5

Figure 1. Receiver operating characteristic (ROC) curves. (a–f) ROC curves for the neutrophil to lym-
phocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), systemic
inflammation index (SII), C-reactive protein to albumin ratio (CAR), and advanced lung cancer inflammation
index (ALI), respectively.
6 Journal of International Medical Research

Table 3. Baseline data. prediction. Multiple studies have demon-

strated that some ratios and scores based
Project Groups N (%)
on peripheral inflammatory cells, including
Age (months) 18 30 (41.67) NLR, PLR, LMR, Hs-mGPS, CAR, and
>18 42 (58.33) SII, have been identified as prognostic bio-
Sex Male 33 (45.83) markers in various solid malignancies such
Female 39 (54.17) as lung cancer, osteosarcoma, and gallblad-
INSS 1þ2 51 (70.83) der cancer.22–25 NLR, PLR, LMR, Hs-
3þ4 21 (29.17)
mGPS, SII, and CAR are the prevailing
MYCN amplification Non-Amp 58 (80.56)
Amplified 14 (19.44)
inflammation prognostic biomarkers based
High risk Non-high 51 (70.83) on routine blood examinations, which can
High 21 (29.17) be widely available without additional
NLR 1.6 49 (68.06) costs.22,26,27 According to the ratio or com-
>1.6 23 (31.94) bination of inflammatory immune and
PLR 170.52 55 (76.39) nutritional factors, these inflammation bio-
>170.52 17 (23.61) markers may be more valuable. CAR com-
LMR 4.6 27 (37.50) bines CRP and ALB, which may be more
>4.6 45 (62.50) accurate and reliable than each independent
Hs-mGPS 0 41 (56.94) indicator alone for prognosis. Hs-mGPS
1–2 31 (43.06)
has been reported to be superior to GPS
SII 694.74 50 (69.44)
>694.74 22 (30.56)
and mGPS for the prognostic evaluation
CAR 0.153 50 (69.44) of solid tumors.26 The advantage of Hs-
>0.153 22 (30.56) mGPS is that the CRP is designed for the
ALI 49.17 28 (38.89) lower cutoff point in the Hs-mGPS, which
>49.17 44 (61.11) is more suitable for special groups of chil-
dren. Yan et al. conducted a systematic
INSS, International Neuroblastoma Staging System;
MYCN, Myc-N proto-oncogene; NLR, neutrophil to
review and showed that high NLR, PLR,
lymphocyte ratio; PLR, platelet to lymphocyte ratio; LMR, CAR, SII, and mGPS, and low LMR
lymphocyte to monocyte ratio; SII, systemic inflammation were associated with poorer survival rates
index; Hs-mGPS, high-sensitivity modified Glasgow in patients with esophageal cancer.28 Bao
Prognostic Score; CAR, C-reactive protein to albumin et al. verified that CAR was a risk factor
ratio; ALI, advanced lung cancer inflammation index.
for poor prognosis, together with clinico-
pathological parameters in gallbladder
stimulate tumor cells to proliferate and cancer.25 In addition, the systemic inflam-
migrate by releasing reactive oxygen species matory response was correlated with the
and altering the extracellular matrix.17 prognosis of pediatric solid tumors, but rel-
Dependent upon their cytotoxic activity atively fewer reports than in adults.9,29
and ability to induce apoptosis, lympho- Several studies have revealed that inflam-
cytes can strengthen tumor immune surveil- matory cytokines play important roles in
lance and control tumor growth through pediatric solid tumors.9,21,30,31 Nayak
natural killer T cells and activated et al. reported that an elevated NLR could
T cells.20 By stimulating tumor angiogene- predict poorer survival rates in pediatric
sis, PLT plays an important role in the solid tumors and might be an independent
stroma formation and cell migration pro- prognostic biomarker.9 Asgharzadeh et al.
cesses in tumors.21 Moreover, some periph- suggested that interactions between tumor
eral immune factors are combined or and inflammatory cells might contribute to
redesigned to further improve prognosis the metastasis of neuroblastoma and are
Qi et al. 7

Table 4. Clinical pathological characteristics between groups.

Low ALI High ALI

Project Groups N (49.17) (>49.17) v2 P-value

Age (months) 18 30 10 20 0.668 0.414

>18 42 18 24
Sex Male 33 12 21 0.163 0.686
Female 39 16 23
INSS stage 1þ2 51 14 37 7.944 0.005
3þ4 21 14 7
MYCN amplification Non-Amp 58 19 39 4.717 0.03
Amplified 14 9 5
High risk Non-high 58 17 41 11.516 0.001
High 14 11 3
NLR 1.6 49 6 43 45.820 <0.001
>1.6 23 22 1
PLR 170.52 55 14 41 17.690 <0.001
>170.52 17 14 3
LMR 4.6 27 19 8 18.016 <0.001
>4.6 45 9 36
Hs-mGPS 0 41 11 30 5.827 0.016
1–2 31 17 14
SII 694.74 50 8 42 36.073 <0.001
>694.74 22 20 2
CAR 0.153 50 12 38 15.264 <0.001
>0.153 22 16 6
Living status Alive 55 13 42 22.803 <0.001
Dead 17 15 2
INSS, International Neuroblastoma Staging System; MYCN, Myc-N proto-oncogene; NLR, neutrophil to lymphocyte ratio;
PLR, platelet to lymphocyte ratio; LMR, lymphocyte to monocyte ratio; SII, systemic inflammation index; Hs-mGPS,
high-sensitivity modified Glasgow Prognostic Score; CAR, C-reactive protein to albumin ratio; ALI, advanced lung cancer
inflammation index.

possible novel therapeutic targets.31 Zheng including six inflammation prognostic bio-
et al. have reported that some inflammatory markers in the multivariate analysis in our
biomarkers, such as CAR, GPS, and study. A possible reason for this is that chil-
Hs-mGPS, were significantly associated dren may have varied blood cell percen-
with the OS of neuroblastoma patients.29 tages. Additionally, an interaction may
Therefore, we also investigated these exist that may weaken the prognostic
inflammatory biomarkers in pediatric neu- value between these inflammatory indices.
roblastoma in our study, and our univariate Therefore, these potential prognostic bio-
variable analyses showed that high NLR, markers in adults may become insignificant
high PLR, low LMR, high Hs-mGPS, in children.
high SII, and high CAR were significantly ALI has been reported to be a potential
correlated with OS in patients with neuro- prognostic biomarker for advanced non-
blastoma. This result is consistent with the small cell lung cancer.11 ALI is composed
previous report.29 However, there was no of the BMI, ALB, and NLR. BMI and
significant prognostic significance after ALB have been demonstrated to be
8 Journal of International Medical Research

Figure 2. Survival curves of the high advanced lung cancer inflammation index (ALI) and low ALI groups.

Table 5. Univariate and multivariate analyses.

Univariate analysis Multivariate analysis

Favorable/
Variables Unfavorable HR (95% CI) P-value HR (95% CI) P-value

Age (months) 18 vs. >18 1.487 (0.548–4.037) 0.436 – –

Sex Male vs. Female 0.595 (0.226–1.569) 0.294 – –
INSS 1 þ 2 vs. 3 þ 4 19.182 (5.457–67.419) <0.001 18.928 (1.949–183.840) 0.011
MYCN Non-Amp vs. 5.361 (2.056–13.978) <0.001 0.987 (0.210–4.643) 0.987
amplification Amplified
High risk Non-high vs. High 28.250 (8.359–95.479) <0.001 3.142 (0.445–22.197) 0.251
NLR 1.6 vs. >1.6 10.522 (3.374–32.813) <0.001 0.161 (0.005–4.918) 0.295
PLR 170.52 vs. >170.52 4.799 (1.839–12.520) 0.001 0.145 (0.12–1.688) 0.123
LMR 4.6 vs. >4.6 0.206 (0.072–0.589) 0.003 1.046 (0.158–6.932) 0.962
Hs-mGPS 0 vs. 1–2 5.442 (1.770–16.73) 0.003 1.512 (0.159–14.418) 0.719
SII 694.74 vs. >694.74 5.776 (2.118–15.755) 0.001 9.299 (0.417–207.563) 0.159
CAR 0.153 vs. >0.153 9.672 (3.297–28.376) <0.001 1.499 (0.137–16.365) 0.740
ALI 49.17 vs. >49.17 0.059 (0.013–0.262) <0.001 0.440 (0.004–0.545) 0.015
INSS, International Neuroblastoma Staging System; MYCN, Myc-N proto-oncogene; NLR, neutrophil to lymphocyte ratio;
PLR, platelet to lymphocyte ratio; LMR, lymphocyte to monocyte ratio; SII, systemic inflammation index; Hs-mGPS,
high-sensitivity modified Glasgow Prognostic Score; CAR, C-reactive protein to albumin ratio; ALI, advanced lung cancer
inflammation index.

important indicators for evaluating the pre- accompanied by no signs at an early stage.
sent nutritional status in advanced In particular, children often cannot express
cancer patients.32–34 Previous studies have unwell symptoms for timely medical exami-
indicated that these two nutritional factors nations. As a result, a large proportion of
may be prognostic factors in various patients are at an advanced stage at the
malignances.35–40 Neuroblastoma may be time of diagnosis. Approximately 24% of
Qi et al. 9

children with neuroblastoma are under- of high malignancy and insidious onset of
weight, malnourished, or even present neuroblastoma, the degree of clinical
with cachexia at diagnosis.33 Thus, the inflammation and nutritional status in this
nutritional status is important for children disease may be different from those of other
with malignances. It is recognized that a tumors.
diminished nutritional status, such as low In the correlation analysis, we found that
BMI and ALB, may contribute to low INSS, MYCN amplification, high risk,
immune function, delayed incision healing, NLR, PLR, LMR, Hs-mGPS, SII, CAR
and disturbed drug metabolism, which may levels, and living status were different
influence the prognosis of pediatric malig- between the low and high ALI groups.
nancy.36 Therefore, compared with a single Hence, ALI might reflect the aggressive
parameter, the ALI is composed of both characteristics of the tumor and may be
inflammation and malnutrition factors associated with the progression of neuro-
and may be a more valuable prognostic bio- blastoma. Furthermore, the KM analysis
marker. Many researchers have also revealed that patients with low ALI had sig-
reported that the ALI is significantly corre- nificantly poorer survival rates than those
lated with poor prognosis in various malig- with high ALI, which was consistent with
nancies, including esophageal cancer, the results of previous studies.11,13,42
colorectal cancer, squamous head and Finally, INSS and ALI were significant
neck cancer, pancreatic carcinoma, and prognostic factors for neuroblastoma
nasopharyngeal carcinoma.12,15,41–44 patients in both univariate and multivariate
Cheng et al. conducted a study on melano- Cox regression analyses. The INSS stage
ma and found that ALI was a strong prog- was recognized as a traditionally important
nostic factor for disease control.12 Feng prognostic factor, including tumor size,
et al. reported that the ALI is still a valu- lymph nodes, and metastasis.5 Advanced
able predictor in esophageal squamous cell INSS stage also indicated the increased
carcinoma.13 Additionally, our team has risk of recurrence and mortality.16
reported that ALI is possibly an indepen- Through our analysis, advanced INSS neu-
dent prognostic biomarker for operable roblastoma patients had tumors with larger
small-cell lung cancer.32 volume that were more likely to metastasize
To the best of our knowledge, our study to the lymph node, which possibly led to the
is the first to report the prognostic value of altered neutrophil and lymphocyte counts.
ALI in children with neuroblastoma. The Moreover, advanced INSS patients with a
cutoff value of ALI in the study was higher tumor burden and distant metastasis
49.17. Cutoff values for ALI in various showed a state of malnutrition. Therefore,
tumors have had a relatively broad range, the two prognostic indices interacted and
including values of 18 in advanced non- might serve as prognostic biomarkers for
small cell lung cancer,11 18.9 in metastatic patients with neuroblastoma.
colorectal cancer,45 20.4 in HPV-negative
head and neck squamous cell carcinoma,15
and 48.2 in small-cell lung cancer.32
Limitations
Neuroblastoma has a relatively higher There are some limitations of our study.
ALI cutoff value compared with many First, this was a single-center retrospective
tumors. This is possibly because children study with a relatively small study popula-
sometimes show different blood cell tion, which may lead to selection bias.
counts and ratios relative to adults. Second, our research was limited to the pre-
Furthermore, because of the characteristics operative ALI data, but the ALI is
10 Journal of International Medical Research

a dynamic biomarker that may show a [Internet]. Treasure Island (FL): StatPearls
degree of fluctuation at different times in Publishing.
the treatment period. Therefore, subsequent 3. Maris JM, Hogarty MD, Bagatell R, et al.
studies should focus particularly on the Neuroblastoma. Lancet 2007; 369: 2106–2120.
4. Maris JM. Recent advances in neuroblasto-
dynamic fluctuation and relevant ALI
ma. N Engl J Med 2010; 362: 2202–2211.
cutoff value at various time points, as well 5. Qi Y and Zhan J. Roles of Surgery in the
as on the identification of more reliable Treatment of Patients With High-Risk
prognostic lamination of neuroblastoma Neuroblastoma in the Children Oncology
patients. Third, there may be differences Group Study: A Systematic Review and
in patient treatments on the basis of the Meta-Analysis. Front Pediatr 2021; 9:
treatment guidelines, which may lead to a 706800.
certain bias. Considering the limitations 6. MacFarland S and Bagatell R. Advances in
mentioned above, large-scale multicenter neuroblastoma therapy. Curr Opin Pediatr
prospective studies are required to further 2019; 31: 14–20.
7. Silverman AM, Nakata R, Shimada H, et al.
strengthen the conclusions of this study.
A galectin-3-dependent pathway upregulates
interleukin-6 in the microenvironment of
Conclusions human neuroblastoma. Cancer Res 2012;
72: 2228–2238.
Our study is the first to reveal that low ALI 8. Liu JQ, Hu A, Zhu J, et al. CD200-CD200R
is correlated with poor prognosis in neuro- Pathway in the Regulation of Tumor Immune
blastoma. Therefore, ALI may be an inde- Microenvironment and Immunotherapy. Adv
pendent prognostic biomarker for patients Exp Med Biol 2020; 1223: 155–165.
with neuroblastoma. 9. Nayak A, McDowell DT, Kellie SJ, et al.
Elevated Preoperative Neutrophil-
Declaration of conflicting interest Lymphocyte Ratio is Predictive of a Poorer
Prognosis for Pediatric Patients with Solid
The authors declare that there is no conflict of
Tumors. Ann Surg Oncol 2017; 24:
interest.
3456–3462.
10. Li X, An B, Zhao Q, et al. Combined fibrin-
Funding ogen and neutrophil-lymphocyte ratio as a
The authors disclosed receipt of the following predictive factor in resectable colorectal ade-
financial support for the research, authorship, nocarcinoma. Cancer Manag Res 2018; 10:
and/or publication of this article: This work 6285–6294.
was supported by the Clinical Medicine Talent 11. Jafri SH, Shi R and Mills G. Advance lung
Training Project funded by the Chinese govern- cancer inflammation index (ALI) at diagno-
ment in 2021. sis is a prognostic marker in patients with
metastatic non-small cell lung cancer
ORCID iD (NSCLC): a retrospective review. BMC
Guochen Duan https://orcid.org/0000-0001- Cancer 2013; 13: 158.
9608-4066 12. Cheng X, Dong Y and Lou F. The
Predictive Significance of the Advanced
Lung Cancer Inflammation Index (ALI) in
References Patients with Melanoma Treated with
1. Whittle SB, Smith V, Doherty E, et al. Immunotherapy as Second-Line Therapy.
Overview and recent advances in the treat- Cancer Manag Res 2021; 13: 173–180.
ment of neuroblastoma. Expert Rev 13. Feng JF, Huang Y and Chen QX. A new
Anticancer Ther 2017; 17: 369–386. inflammation index is useful for patients
2. Mahapatra S and Challagundla KB. with esophageal squamous cell carcinoma.
Neuroblastoma. 2021 Jul 17. In: StatPearls Onco Targets Ther 2014; 7: 1811–1815.
Qi et al. 11

14. Kusunoki K, Toiyama Y, Okugawa Y, et al. neutrophil-to-lymphocyte ratio in anaplastic

Advanced Lung Cancer Inflammation Index thyroid carcinoma. Endocrine 2020; 70:
Predicts Outcomes of Patients With 115–122.
Colorectal Cancer After Surgical Resection. 25. Bao Y, Yang J, Duan Y, et al. The C-reac-
Dis Colon Rectum 2020; 63: 1242–1250. tive protein to albumin ratio is an excellent
15. Gaudioso P, Borsetto D, Tirelli G, et al. prognostic predictor for gallbladder cancer.
Advanced lung cancer inflammation index Biosci Trends 2021; 14: 428–435.
and its prognostic value in HPV-negative 26. Cui Y, Li J, Cao YH, et al. Predictive and
head and neck squamous cell carcinoma: a Prognostic significance of high-sensitivity
multicentre study. Support Care Cancer modified Glasgow Prognostic Score (HS-
2021; 29: 4683–4691. mGPS) in advanced gastric cancer patients
16. Von Elm E, Altman DG, Egger M, et al. treated with neoadjuvant chemotherapy.
The Strengthening the Reporting of Zhonghua Zhong Liu Za Zhi 2017; 39:
Observational Studies in Epidemiology 195–200.
(STROBE) statement: guidelines for report- 27. Jomrich G, Gruber ES, Winkler D, et al.
ing observational studies. Ann Intern Med Systemic Immune-Inflammation Index
2007; 147: 573–577. (SII) Predicts Poor Survival in Pancreatic
17. Singh N, Baby D, Rajguru JP, et al. Cancer Patients Undergoing Resection.
Inflammation and cancer. Ann Afr Med J Gastrointest Surg 2020; 24: 610–618.
2019; 18: 121–126. 28. Jiang Y, Xu D, Song H, et al. Inflammation
18. De Vries NL, Van Unen V, Ijsselsteijn ME,
and nutrition-based biomarkers in the prog-
et al. High-dimensional cytometric analysis
nosis of oesophageal cancer: a systematic
of colorectal cancer reveals novel mediators
review and meta-analysis. BMJ Open 2021;
of antitumour immunity. Gut 2020; 69:
11: e48324.
691–703.
29. Zheng C, Liu S, Feng J, et al. Prognostic
19. Riemann D, Cwikowski M, Turzer S, et al.
Value of Inflammation Biomarkers for
Blood immune cell biomarkers in lung
Survival of Patients with Neuroblastoma.
cancer. Clin Exp Immunol 2019; 195:
Cancer Manag Res 2020; 12: 2415–2425.
179–189.
30. Guo F, Zhang J, Wang L, et al.
20. Yoon CI, Park S, Cha YJ, et al. Associations
Identification of differentially expressed
between absolute neutrophil count and
lymphocyte-predominant breast cancer. inflammatory factors in Wilms tumors and
Breast 2020; 50: 141–148. their association with patient outcomes.
21. Khandia R and Munjal A. Interplay Oncol Lett 2017; 14: 687–694.
between inflammation and cancer. Adv 31. Asgharzadeh S, Salo JA, Ji L, et al. Clinical
Protein Chem Struct Biol 2020; 119: significance of tumor-associated inflamma-
199–245. tory cells in metastatic neuroblastoma.
22. Yapar A, Tokgoz MA, Yapar D, et al. J Clin Oncol 2012; 30: 3525–3532.
Diagnostic and prognostic role of neutro- 32. Hu Z, Wu W, Zhang X, et al. Advanced
phil/lymphocyte ratio, platelet/lymphocyte Lung Cancer Inflammation Index is a
ratio, and lymphocyte/monocyte ratio in Prognostic Factor of Patients with Small-
patients with osteosarcoma. Jt Dis Relat Cell Lung Cancer Following Surgical
Surg 2021; 32: 489–496. Resection. Cancer Manag Res 2021; 13:
23. Wang C, Jin S, Xu S, et al. High Systemic 2047–2055.
Immune-Inflammation Index (SII) 33. Bauer J, Jurgens H and Fruhwald MC.
Represents an Unfavorable Prognostic Important aspects of nutrition in children
Factor for Small Cell Lung Cancer Treated with cancer. Adv Nutr 2011; 2: 67–77.
with Etoposide and Platinum-Based 34. Sala A, Pencharz P and Barr RD. Children,
Chemotherapy. Lung 2020; 198: 405–414. cancer, and nutrition–A dynamic triangle in
24. Yamazaki H, Sugino K, Matsuzu K, et al. review. Cancer-Am Cancer Soc 2004; 100:
Inflammatory biomarkers and dynamics of 677–687.
12 Journal of International Medical Research

35. Bosaeus I, Daneryd P, Svanberg E, et al. score matching analysis. Clin Nutr 2021; 40:
Dietary intake and resting energy expendi- 1130–1136.
ture in relation to weight loss in unselected 41. Pian G, Hong SY and Oh SY. Prognostic
cancer patients. Int J Cancer 2001; 93: value of advanced lung cancer inflammation
380–383. index in patients with colorectal cancer liver
36. Canedo G, Palomino PL, Puerta ML, et al. metastases undergoing surgery. Tumori
Validity and Reliability of a Nutritional 2022: 108: 56–62.
Screening Tool (SCAN) in Children Newly 42. Hua X, Chen J, Wu Y, et al. Prognostic role
Diagnosed with Cancer. Nutr Cancer 2021; of the advanced lung cancer inflammation
74: 1–12. index in cancer patients: a meta-analysis.
37. Rogers PC. Importance of nutrition in pedi- World J Surg Oncol 2019; 17: 177.
atric oncology. Indian J Cancer 2015; 52: 43. Topkan E, Mertsoylu H, Ozdemir Y, et al.
Prognostic Usefulness Of Advanced Lung
176–178.
Cancer Inflammation Index In Locally-
38. Jank BJ, Kadletz L, Schnoll J, et al.
Advanced Pancreatic Carcinoma Patients
Prognostic value of advanced lung cancer
Treated With Radical Chemoradiotherapy.
inflammation index in head and neck squa-
Cancer Manag Res 2019; 11: 8807–8815.
mous cell carcinoma. Eur Arch
44. Topkan E, Ozdemir Y, Kucuk A, et al.
Otorhinolaryngol 2019; 276: 1487–1492. Low Advanced Lung Cancer Inflammation
39. Tsai YT, Hsu CM, Chang GH, et al. Index Predicts Poor Prognosis in Locally
Advanced Lung Cancer Inflammation Advanced Nasopharyngeal Carcinoma
Index Predicts Survival Outcomes of Patients Treated with Definitive Concurrent
Patients With Oral Cavity Cancer Chemoradiotherapy. J Oncol 2020; 2020:
Following Curative Surgery. Front Oncol 3127275.
2021; 11: 609314. 45. Shibutani M, Maeda K, Nagahara H, et al.
40. Yin C, Toiyama Y, Okugawa Y, et al. The prognostic significance of the advanced
Clinical significance of advanced lung lung cancer inflammation index in patients
cancer inflammation index, a nutritional with unresectable metastatic colorectal
and inflammation index, in gastric cancer cancer: a retrospective study. BMC Cancer
patients after surgical resection: A propensity 2019; 19: 241.