Original Article

Endostar improved efficacy of concurrent chemoradiotherapy with

vinorelbine plus carboplatin in locally advanced lung squamous
cell carcinoma patients with high serum Lp(a) concentration
Hailing Xu1,2, Dongqing Lv2#, Yinnan Meng1,3, Miao Wang1,3, Wei Wang1,3, Chao Zhou1,3, Suna Zhou1,3,
Xiaofeng Chen4, Haihua Yang1,3#
1
Laboratory of Cellular and Molecular Radiation Oncology, Radiation Oncology Institute of Enze Medical Health Academy, 2Department of
Pulmonary Medicine, Enze Hospital, 3Department of Radiation Oncology, 4Department of Cardiology, Affiliated Taizhou hospital of Wenzhou
Medical University, Taizhou 317000, China
Contributions: (I) Conception and design: H Yang, D Lv; (II) Administrative support: All authors; (III) Provision of study materials or patients: H
Yang, D Lv; (IV) Collection and assembly of data: H Xu, Y Meng, M Wang, W Wang, C Zhou, S Zhou; (V) Data analysis and interpretation: H Xu,
M Wang, W Wang, H Yang; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.
#
These authors contributed equally to this work.
Correspondence to: Haihua Yang, MD. Laboratory of Cellular and Molecular Radiation Oncology, Radiation Oncology Institute of Enze Medical
Health Academy, Department of Radiation Oncology, Affiliated Taizhou Hospital of Wenzhou Medical University, Taizhou 317000, China.
Email: [email protected]; Dongqing Lv, MD. Department of Pulmonary Medicine, Enze Hospital, Affiliated Taizhou Hospital of Wenzhou
Medical University, Taizhou 317000, China. Email: [email protected].

Background: The role of vascular targeting therapy combined with concurrent chemoradiotherapy (CRT)
has produced many inconsistent results in locally advanced non-small-cell lung cancer (NSCLC), especially
in lung squamous cell carcinoma (LSCC). Lipoprotein (a) [Lp(a)] may be critical in the development
of tumor angiogenesis, and its levels are individualized and determined genetically. This study aimed to
determine whether Lp(a) is correlated with effects of recombinant human endostatin (Endostar) combined
with concurrent CRT for locally advanced LSCC.
Methods: Patients with locally advanced LSCC from December 2008 to December 2017 were
retrospectively analyzed. Patients were divided into two groups: (I) a chemoradiotherapy group (CRT
group) which received weekly vinorelbine and carboplatin concurrently with radiotherapy 60Gy, and
(II) an Endostar in combination with chemoradiotherapy group (ECRT group) which received Endostar
intravenous drip for 1–14 days (every 3 weeks) concurrently with CRT. Fasting venous blood samples for
serum Lp(a) in all patients were collected before the treatment. The effect of Endostar was assessed by
stratified analysis.
Results: A total of 94 patients were recruited in this study. There were 59 cases in the CRT group and
35 cases in the ECRT group. Overall, the median progression-free survival (PFS) was 9.6 vs. 14.2 months
(P=0.0671), and the overall survival (OS) was 15.0 vs. 20.6 months (P=0.114), in the CRT and ECRT groups
respectively. The median of Lp(a) was 218 mg/L. In patients with serum Lp(a) less than 218 mg/L, the
median PFS was 10.0 vs. 9.4 months (P=0.406), and the OS was 15.4 vs. 16.3 months (P=0.958) in the CRT
and ECRT groups, respectively. However, in patients with serum Lp(a) higher than 218mg/L, the median
PFS was 9.0 vs.15.8 months (P=0.011), and the OS was 14.0 vs. 21.1 months (P=0.055), in the CRT and
ECRT groups, respectively. Cox proportional hazard model analysis revealed that a high concentration of
Lp(a), ≥218 mg/L, is a prognostic factor for PFS [hazard rate (HR), 0.43 (0.23–0.81)] and OS [HR, 0.52
(0.27–0.98)] in locally advanced LSCC (P<0.05).
Conclusions: The serum concentration of Lp(a) may serve as a biomarker to identify the patients who
would benefit from Endostar treatment with concurrent CRT in stage III LSCC.

© Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2020;9(2):298-307 | http://dx.doi.org/10.21037/apm.2020.01.16
Annals of Palliative Medicine, Vol 9, No 2 March 2020 299

Keywords: Recombinant human endostatin (Endostar); lipoprotein(a) [Lp(a)]; chemoradiotherapy (CRT); lung
squamous cell carcinoma (LSCC)

Submitted Sep 29, 2019. Accepted for publication Jan 18, 2020.
doi: 10.21037/apm.2020.01.16
View this article at: http://dx.doi.org/10.21037/apm.2020.01.16

Introduction superiority of Endostar combined with weekly vinorelbine

plus carboplatin and radiation in locally advanced LSCC
Lung cancer is the leading malignant disease in the world
patients still needs further confirmation and exploring the
with high mortality and morbidity. Non-small-cell lung
prognostic factors for this regimen could offer urgently
cancer (NSCLC) accounts for approximately 80% of the
needed benefit.
subtypes of lung cancer, among which lung squamous cell
Lipoprotein (a) [Lp(a)], composed of a low-density
carcinoma (LSCC) accounts for about 30%. Most LSCC
lipoprotein (LDL)-core with an apolipoprotein A
patients are preliminarily diagnosed at an advanced stage
[apo(A)] attached covalently to an apolipoprotein B-100
with a mere 5–10% rate of 5-year survival. With fewer
[apo(B-100)], has been found to be relevant for cancer
driver gene mutations than adenocarcinoma and few new
and have cardiovascular potency (12), even though its
approaches to explore, there are only several therapies
antiangiogenic and antitumoral effects are still controversial
for inoperable advanced LSCC, including chemotherapy,
and inconsistent. Marrer et al. (13) discovered no evident
chemoradiotherapy (CRT), and target therapy, resulting in
association between Lp(a) and cancer, whereas men with
an overall dissatisfactory survival time. Of late, CRT has
the highest Lp(a) levels seem to have the highest risk of
been the first-line therapy for advanced LSCC patients
lung cancer. Also, attributable to the increasing endothelial
showing 10–19 months of median progression-free survival
cell motility and promotion of angiogenesis through fibrin
(PFS) and 14–29 months of median overall survival (OS)
deposition, the concentration of Lp(a) has been found to
(1,2). However, treatment for CRT in locally advanced
be significantly elevated in lung cancer when compared
LSCC has plateaued, and so the modest benefit potentially
with the normal population, and in stage IV patients when
offered by combination therapy attracted our attention.
compared with the stage I group in breast cancer (14,15).
Recombinant human endostatin (Endostar), a new anti-
In addition to these, our previous study demonstrated an
angiogenic target drug, is efficient in blocking angiogenesis,
independently positive correlation between tumor stage and
inhibiting tumor endothelial cell proliferation, and
Lp(a) levels in lung cancer (16). Therefore, the increased
suppressing primary tumor and metastatic growth in lung
value of Lp(a) in lung cancer and its underlying mechanisms
cancer with less risk of life-threatening side effects. Its
should be emphasized in future studies.
underlying anti-tumor mechanisms are vascular endothelial
Given this, our present study aimed to explore whether
growth factor (VEGF) signaling pathway, anti-apoptosis,
Endostar could improve the efficacy of concurrent CRT
and other processes (3,4). It has been reported that
in locally advanced LSCC, and proposes a hypothesis that
Endostar combined with platinum-doublet chemotherapy,
high Lp(a) concentration could be a prognostic factor for
including vinorelbine, gemcitabine, paclitaxel, can prolong
stage III LSCC patients in response to the regimen above.
the survival time for those patients with good performance
status in advanced LSCC, and has been recommended as the
first-line choice, boasting 6.0–7.2 and 13.6–19.0 months of Methods
median PFS and OS, respectively (5,6). However, the trend
Patients and therapy
of improved survival time in advanced NSCLC patients
administered maintenance treatment is still disputed (7,8). This study retrospectively analyzed the locally advanced
Owing to its potential and promising benefits, emerging LSCC patients from December 2008 to December 2017.
studies, including the latest HELPER study (9), have added A total of 94 patients pathologically confirmed with locally
insight into the effects of Endostar in combination with advanced stage IIIA or IIIB LSCC were enrolled regardless
CRT in advanced NSCLC patients (10,11). However, the of lines of treatment. The patients were divided into two

© Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2020;9(2):298-307 | http://dx.doi.org/10.21037/apm.2020.01.16
300 Xu et al. Endostar improved efficacy of high Lp(a) LSCC

groups: (I) the chemoradiotherapy group (CRT group) who the log‑rank test in the univariate analysis and stratified
received weekly vinorelbine (12.5 mg/m 2/d)/carboplatin analysis. The Cox proportional hazards model was used
[area under drug curve (AUC) =2] concurrently with subsequently to assess the contribution of each potential
radiotherapy consisting of 60 Gy total doses in 6 weeks, and prognostic factor for survival. All P values were two-sided.
(II) the Endostar in combination with chemoradiotherapy A P value ≤0.05 was considered statistically significant.
group (ECRT group) who received Endostar intravenous
drip 1–14 days (7.5 mg/m2/d, 3-week repetition program)
Results
on the basis of the CRT group. Additionally, relevant
fasting venous blood samples including Lp(a) were collected Patients’ demographics and baseline characteristics
before the treatment. This study was performed following
The patients’ characteristics at baseline are summarized in
an institutional ethics review board approved protocol.
Table 1. A total of 94 LSCC patients were enrolled in this
study. There were 59 cases in the CRT group, including
Evaluation criteria 57 men and 2 women, while there were 35 cases in ECRT
The primary endpoint was to explore a biomarker for the group, including 33 men and 2 women. In terms of age,
above setting regimen in LSCC patients while the second sex, Karnofsky performance status (KPS), smoke status,
endpoints were PFS, OS, objective response rate (ORR) and Lp(a), there was no difference of these baseline
and adverse events (AEs). PFS was defined as the time to characteristics between the two groups according to chi-
the patient’s first clinical progression or death from any square analysis. The median Lp(a) was 218 mg/L. On the
cause after concurrent CRT with or without Endostar. basis of Lp(a), the stratification analysis was represented,
If there was no progression or the patient survived until and there was also no significant difference between groups.
our deadline was met, PFS was defined as the last date of Regarding the compliance of patients, the median
confirmation of no progression. OS was defined as the time follow-up time of patients was 20.25 months, while 26 of
to death of any cause or most recent follow-up. According 59 and 22 of 35 patients completed the planned treatment
to response evaluation criteria in solid tumors (RECIST) schedule of concurrent CRT in the CRT and ECRT group,
version 1.1, the response to treatment could be clarified respectively. The ORR was achieved in 86.4% vs. 82.9%
as complete response (CR), partial response (PR), stable of patients in the CRT and ECRT group respectively.
disease (SD), and progressive disease (PD) at the first month The DCR was 93.2% vs. 91.4% of patients in the CRT
after treatment. ORR was defined as the sum of the CR and ECRT group respectively. We observed the CR
and PR percentages, while disease control rate (DCR) was after treatment of the CRT group in 5 patients, PR in
defined as the sum of the of CR, PR, and SD percentages. 46 patients, SD in 4 patients, and PD in 4 patients. After
AEs including nausea and vomiting, myelosuppression, treatment in the ECRT group, there was PR in 29 patients,
radiation pneumonitis, radiation esophagitis, hypertension, SD in 3 patients, and PD in 3 patients. The complete lack
and arrhythmia were recorded and classified into grades 0–5. of CR in the experimental group might have been due to
the limited number of patients (Table 2).

Statistical analysis
Survival
All statistical procedures were performed on the statistical
package for the social sciences (SPSS) version 20.0 (SPSS In the CRT and ECRT group respectively, the median PFS
Inc., Chicago, IL, USA). Non-normal distributions were and OS were 9.6 vs. 14.2 months (P=0.0671) (Figure 1A)
expressed as median and range, except for age, which was and 15.0 vs. 20.6 months (P=0.114) (Figure 1B).
represented as the median and extreme. Comparisons In patients with less than 218 mg/L, the median PFS
between groups were performed by analysis of the and OS were 10.0 vs. 9.4 months (P=0.406), (Figure 2A) and
nonparametric test for non-normally distributed variables 15.4 vs. 16.3 months (P=0.958) (Figure 2B) in the CRT and
as appropriate. The chi-square test was used for categorical ECRT group, respectively. However, in patients with more
variables. As for the PFS and OS, event-time distributions than 218 mg/L, the median PFS and OS were 9.0 vs.15.8
were estimated by the Kaplan-Meier method and the months (P=0.011) (Figure 2C), and 14.0 vs. 21.1 months
association between groups and survival was assessed by (P=0.055) (Figure 2D) in the CRT and ECRT group

© Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2020;9(2):298-307 | http://dx.doi.org/10.21037/apm.2020.01.16
Annals of Palliative Medicine, Vol 9, No 2 March 2020 301

Table 1 Patients’ baseline characteristics (N)

ECRT group CRT group
Characteristics P
< 218 ≥ 218 P < 218 ≥ 218 P

Age(years) 0.69 0.35 0.45

<62 5 10 15 15

≥62 8 12 18 11

Sex 1.00 0.50 0.99

Male 12 21 31 26

Female 1 1 2 0

KPS 0.065 0.87 0.33

70 2 3 4 9

80 8 15 23 14

90 3 4 6 3

Stage 0.57 0.73 0.48

IIIA 2 2 15 13

IIIB 11 20 18 13

Smoke 0.99 1.00 1.00

Non-smoke 6 8 4 4

Smoke 7 14 29 22
CRT group, chemoradiotherapy group; ECRT group, Endostar in combination with chemoradiotherapy group.

Table 2 Response to treatment according to RECIST v.1.1

Group CR PR SD PD ORR DCR

ECRT group, n (%) NA 29 (82.9) 3 (8.6) 3 (8.6) 29 (82.9) 32 (91.4)

CRT group, n (%) 5 (8.5) 46 (78.0) 4 (6.8) 4 (6.8) 51 (86.4) 55 (93.2)

CRT group, chemoradiotherapy group; ECRT group, Endostar in combination with chemoradiotherapy group; CR, complete response; PR,
partial response; SD, stable disease; PD, progression disease; ORR, objective response rate; DCR, disease control rate; NA, not available.

respectively. AEs

The AEs are outlined in Table 3. Overall, the most common

Cox proportional hazard model analysis grade ≥3 AE was myelosuppression in both the CRT group
As is shown in the forest map analysis of PFS (Figure 3A), (25.4%) and ECRT group (37.1%). Meanwhile, the number
factors including age, sex, KPS, smoking status, stage, of patients with grade ≥3 AEs was 19 (32.2%) and 12 (34.3%)
and Lp(a) were analyzed by Cox proportional hazards in the CRT and ECRT group (P=0.658), respectively. For
model. The results show that a high concentration of pneumonitis grade ≥3 AEs, there were 3 patients (5.1%) vs.
Lp(a) (≥218 mg/L) was a prognostic for patients with 1 patient (2.9%) in the CRT and ECRT group, respectively.
advanced LSCC [hazard rate (HR), 0.43(0.23–0.81)] No grade ≥3 adverse cardiovascular events including
(P<0.05). Meanwhile, similar outcomes for OS [HR, hypertension and arrhythmia were observed. There were no
0.52(0.27–0.98)] are displayed (P<0.05) in Figure 3B. grade 5 events in either group.

© Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2020;9(2):298-307 | http://dx.doi.org/10.21037/apm.2020.01.16
302 Xu et al. Endostar improved efficacy of high Lp(a) LSCC

A 100 B 100
90 90
80 80
70 70
60 60
PFS (%)
50

OS (%)
50
40 40
30 30
20 20
10 10
0 0
0 12 24 36 48 60 72 0 12 24 36 48 60 72 84 96
Months Months

Figure 1 The PFS (A) and OS (B) in the CRT group and ECRT group. PFS, progression-free survival; OS, overall survival; CRT group,
chemoradiotherapy group; ECRT group, Endostar in combination with chemoradiotherapy group; HR, hazard rate; CI, confidence interval.

A 100 B 100
90 90
80 80
70 70
60 60
PFS (%)

50 50
OS (%)

40 40
30 30
20 20
10 10
0 0
0 12 24 36 48 60 72 0 12 24 36 48 60 72 84 96
Months Months
C 100
D 100
90
90
80 80
70 70
60 60
PFS (%)

50 50
OS (%)

40 40
30 30
20 20
10 10
0 0
0 12 24 36 48 60 72 0 12 24 36 48 60 72 84 96
Months Months

Figure 2 Stratified analysis of PFS (A) and OS (B) in the CRT group and ECRT group by low concentration of Lp(a); stratified analysis
of PFS (C) and OS (D) in the CRT group and ECRT group by a high concentration of Lp(a). PFS, progression-free survival; OS, overall
survival; Lp(a), lipoprotein(a); CRT group, chemoradiotherapy group; ECRT group, Endostar in combination with chemoradiotherapy
group; HR, hazard rate; CI, confidence interval.

Discussion especially those with LSCC. Until now, CRT was

recommended as the first line for stage III LSCC patients.
This study proved that the regimen of concurrent radiation
As for the sequence of chemotherapy and radiotherapy,
combined with vinorelbine plus cisplatin with the addition numerous studies have found that concurrent CRT could
of Endostar can be tolerated in patients with locally gain superior OS outcomes as a result of better locoregional
advanced stage III LSCC. The concentration of Lp(a) may control with mildly increased risk of esophageal toxicity
play a valuable role in identifying suitable patients for this (17,18). It was observed that liposome-paclitaxel and
regimen. carboplatin concurrent with radiotherapy showed a
Patients with unresectable locally NSCLC have significant anti-tumor effect in LSCC patients with
dissatisfactory survival times and poor quality of life, manageable toxicities, and had 17.0 months of estimated

© Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2020;9(2):298-307 | http://dx.doi.org/10.21037/apm.2020.01.16
Annals of Palliative Medicine, Vol 9, No 2 March 2020 303

33

Figure 3 Cox proportional hazardsmodel analysis on PFS (A) and OS (B) in the CRT group and ECRT group. *, analyzed data of females
were not presented due to limited numbers. PFS, progression-free survival; OS, overall survival; CRT group, chemoradiotherapy group;
ECRT group, Endostar in combination with chemoradiotherapy group; KPS, Karnofsky performance status; Lp(a), lipoprotein(a); HR,
hazard rate; CI, confidence interval; NA, not available.

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304 Xu et al. Endostar improved efficacy of high Lp(a) LSCC

Table 3 AEs
CRT group (grade) ECRT group (grade)
Toxicity
0 1 2 3 4 5 0 1 2 3 4 5

Nausea/vomiting 30 23 2 4 0 0 27 3 4 1 0 0

Myelosuppression 4 21 19 14 1 0 1 11 10 12 1 0

Hypertension 58 1 0 0 0 0 32 2 1 0 0 0

Arrhythmia 57 1 1 0 0 0 33 1 1 0 0 0

Esophagitis 11 26 18 4 0 0 13 12 9 1 0 0

Pneumonitis 16 27 13 3 0 0 16 14 4 1 0 0
AEs, adverse events; CRT group, chemoradiotherapy group; ECRT group, Endostar in combination with chemoradiotherapy group.

median PFS, 29.0 months of median OS, and 68.4% of of a given drug’s cytotoxic effects, contributing to increasing
ORR (1). However, combination therapy was proven to be intra-tumor blood perfusion and improving the tumor
more efficient than CRT with improved survival time and hypoxia environment. This period begins on about the 4th to
similar treatment-toxicity. the 10th day after treatment of Endostar in vivo and vitro (22).
Angiogenesis inhibitors, such as bevacizumab, cetuximab, Endostar was found to enhance radiosensitivity in Lewis
Endostar etc., play a significant role in combination therapy lung carcinomas and clinical trials (23-25). After attempting
for lung cancer patients. Random trials have demonstrated to take advantage of this phenomenon, numerous studies
that the addition of bevacizumab to chemotherapy demonstrated that Endostar in combination with CRT,
significantly improved the OS to 24.3 months in patients, whether it was paclitaxel, etoposide, or docetaxel, exerted
regretfully with increased hemorrhage toxicity particularly a profound effect in stage III NSCLC patients (11,26).
in the squamous subtype (19). Cetuximab combined Further to this, the gene delivery of Endostar into even a
with vinorelbine plus cisplatin could obtain a statistically minority of tumor cells may be also an effective strategy
significant improvement in OS and better control rate to prevent progression of micrometastases to macroscopic
for metastatic NSCLC, especially in a high expression disease (27). Consistent with previous results, we observed
ofepidermal growth factor receptor (EGFR) (≥200) in the that in the CRT and ECRT group, the median PFS and
FLEX trial (20). The feasibility of cetuximab with CRT OS were 9.6 vs. 14.2 months (P=0.067), and 15.0 vs.
regiment was also demonstrated in radiation therapy 20.6 months (P=0.114) respectively. This suggests that
oncology group (RTOG) 0324 with a 22.7-month median Endostar combined with CRT could modestly prolong PFS
OS (21). However, a negative outcome of cetuximab with and OS and bring promising therapy for LSCC patients,
CRT was observed with more AEs in RTOG 0617. Thus, although there was no statistically significant difference
whether cetuximab can offer a clear benefit of survival between the two groups.
time in NSCLC patients, even with the high expression of In addition, grade ≥3 AEs were observed in 32.2% vs.
EGFR, is still ambiguous. 34.3% of patients (P=0.658) in the CRT and ECRT group
The brand-new angiogenesis inhibitor, Endostar, has respectively. Pneumonitis AEs grade ≥3 were 3/59 (5.1%)
been shown to normalize vascular structure with reduced vs. 1/35 (2.9%) in the CRT and ECRT group respectively.
vessel diameter, increased pericyte coverage or proximity, Esophagitis grade ≥3 AEs were 4/59 (6.8%) vs. 1/35 (2.9%)
and normalize basement membrane. It can also modulate in the CRT and ECRT group respectively. There were
functions of the tumor vascular network, by promoting no ≥ grade 3 cardiotoxicity events recorded and no grade
oxygenation, reducing permeability, and improving the 5 events. This indicates that the addition of Endostar into
delivery efficiency of drugs, which are the basis of its anti- CRT would not add up toxicities for advanced LSCC
angiogenic and anti-tumor effects with a low rate of AEs. patients with improved survival time. Even compared with
There is a window phase after treatment with Endostar some notable studies, Endostar in combination with weekly
during which the tumor vascular network is normalized with vinorelbine plus carboplatin may provide better security.
good vascular structure and is then conducive to the exertion Of course, it cannot be denied that the limited number

© Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2020;9(2):298-307 | http://dx.doi.org/10.21037/apm.2020.01.16
Annals of Palliative Medicine, Vol 9, No 2 March 2020 305

of patients enrolled in our study, especially in the ECRT with weekly vinorelbine plus carboplatin. This marker may
group, might have led to the low incidence of pneumonitis prove to be a valuable asset in treatment decision‑making,
or esophagitis. patient selection, and the design of clinical trials.
Interestingly, a meaningful association between the
concentration of Lp(a) and the efficacy of LSCC in response
Conclusions
to Endostar in combination with weekly vinorelbine plus
carboplatin was observed. It was expected that there would For patients with locally advanced LSCC, our study
be a higher concentration of Lp(a) in lung cancer compared demonstrated that the integration of Endostar and concurrent
with the normal population. It was also reported that there CRT with weekly vinorelbine plus carboplatin could be
is a significant association between Lp(a) and the presence effective and safe, especially in a high Lp(a) concentration.
and stage of lung cancer. Some investigators have explained The concentration of Lp(a) may be a prognostic factor
such effects may play a significant role in influencing cancer for the Endostar combination with concurrent CRT in
progression and extension rather than tumorigenesis. advanced stage III LSCC. We recommend the median Lp(a)
Moreover, the components of Lp(a) including LDL and in patients (218 mg/L) as the diacritical point. To be sure,
apo(B-100) were shown to have a relationship with anti- these conclusions still should be prospectively validated and
angiogenesis effects and the incidence of lung cancer. This amended in a larger cohort study.
is consistent with our results showing that high Lp(a) may
be a favorable prognostic factor for locally advanced LSCC
Acknowledgments
patients. We chose the median of Lp(a), 218 mg/L, as the
cut-off. In patients with less than 218 mg/L, the median The authors gratefully acknowledge Dr. Feng-Ming
PFS and OS were 10.0 vs. 9.4 months (P=0.406) (Figure 2A), (Spring) Kong, from Case Western Reserve University for
and 15.4 vs. 16.3 months (P=0.958) (Figure 2B) in the CRT editorial assistance of the abstract.
and ECRT group respectively. In patients with more than Funding: This work was supported in part by the Chinese
218 mg/L, the median PFS and OS were 9.0 vs.15.8 months National Science Foundation Projects (NSFC 81874221
(P=0.011) (Figure 2C), and 14.0 vs. 21.1 months (P=0.055) and 81872458), the Zhejiang Provincial Medicine and
(Figure 2D) in the CRT and ECRT group respectively. Health Foundation (2015KYA240), and the Science and
However, the underlying mechanisms of Lp(a) in LSCC Technology Agency of Taizhou City (15yw01), China.
still need further exploration.
To our knowledge, the study was the first to evaluate
Footnote
the efficacy of an Endostar in combination with weekly
vinorelbine plus carboplatin and radiation regimen for Conflicts of Interest: The authors have no conflicts of interest
patients with LSCC, and to identify a common biology to declare.
biomarker as a prognostic factor for LSCC patients.
However, there were some limitations to the study. Firstly, Ethical Statement: The authors are accountable for all
it was a retrospective design rather than a prospective aspects of the work in ensuring that questions related
one, leading to a limited number of patients being in the to the accuracy or integrity of any part of the work are
ECRT group, although there was no difference in baseline appropriately investigated and resolved. This study was
characteristics. Also, the tolerance of consolidation performed following an institutional ethics review board
therapy in patients with LSCC after treatment is thus approved protocol (K20130227).
far unknown. Furthermore, there were several female
patients in our study. Several studies have revealed a close Open Access Statement: This is an Open Access article
association between levels of estrogen and lipids (28), so distributed in accordance with the Creative Commons
that we could have either enrolled more female patients Attribution-NonCommercial-NoDerivs 4.0 International
for the stratification analysis or excluded their statistics License (CC BY-NC-ND 4.0), which permits the non-
altogether. commercial replication and distribution of the article with
In summary, we surmise that locally advanced LSCC the strict proviso that no changes or edits are made and the
patients with a high concentration of Lp(a) may benefit more original work is properly cited (including links to both the
from combined therapy with Endostar and concurrent CRT formal publication through the relevant DOI and the license).

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306 Xu et al. Endostar improved efficacy of high Lp(a) LSCC

See: https://creativecommons.org/licenses/by-nc-nd/4.0/. of inflammation-based prognostic indices in locally

advanced non-small-lung cancer treated with endostar
and concurrent chemoradiotherapy. Mol Clin Oncol
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Cite this article as: Xu H, Lv D, Meng Y, Wang M, Wang W,

Zhou C, Zhou S, Chen X, Yang H. Endostar improved efficacy
of concurrent chemoradiotherapy with vinorelbine plus
carboplatin in locally advanced lung squamous cell carcinoma
patients with high serum Lp(a) concentration. Ann Palliat Med
2020;9(2):298-307. doi: 10.21037/apm.2020.01.16

© Annals of Palliative Medicine. All rights reserved. Ann Palliat Med 2020;9(2):298-307 | http://dx.doi.org/10.21037/apm.2020.01.16