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ORIGINAL ARTICLE
Real-world study of treatment and outcome of type B2 +B3
thymoma: The neglected part of thymoma
Ke Zhao
1
| Yeye Chen
1
| Lei Liu
1
| Guige Wang
1
| Jiaqi Zhang
1
|
Mengxin Zhou
1
| Xuehan Gao
1
| Ke Rao
2
| Libing Yang
1
| Chao Guo
1
|
Ye Zhang
1
| Cheng Huang
1
| Hongsheng Liu
1
| Shanqing Li
1
1
Department of Thoracic Surgery, Peking Union
Medical College Hospital, Chinese Academy of
Medical Science & Peking Union Medical College,
Beijing, China
2
Peking Union Medical College Hospital, Chinese
Academy of Medical Science & Peking Union
Medical College, Beijing, China
Correspondence
Shanqing Li, Department of Thoracic Surgery,
Peking Union Medical College Hospital, Chinese
Academy of Medical Science and Peking Union
Medical College, No.1 Shuaifuyuan, Dongcheng
District, Beijing, 100730, China.
Email: lishanqing@pumch.cn
Funding information
National High Level Hospital Clinical Research
Funding, Grant/Award Numbers: 2022-PUMCH-
B-011, 2022-PUMCH-B-012
Abstract
Background: This study aimed to examine the treatment and prognosis of patients
with type B2 +B3 thymoma and compare it with those patients with type B2 and B3
thymoma.
Methods: We conducted a retrospective analysis of the results of 39 patients with type
B2 +B3 thymoma, 133 patients with type B2 thymoma, and 64 patients with type B3
thymoma. The Kaplan–Meier technique was used to generate survival curves. For
multivariate analysis, the Cox proportional hazard model was applied.
Results: With a median follow-up of 60 months (range: 1–128 months), the percent-
age of patients with tumor, node, metastasis (TNM) stage III and IV disease gradually
increased from 19.5% to 25.6% to 35.9% among those with histological subtypes B2,
B2 +B3, and B3, respectively, p=0.045. Twenty-three patients experienced recur-
rence or metastasis. The total 10-year progression-free survival (PFS) rates were 86.0%
overall (85.0% in type B2, 87.2% in type B2 +B3, and 87.5% in type B3). Age, R0
resection, and Masaoka–Koga stage were found to have a significant on PFS in all
patients. There was no statistically significant difference in PFS between different his-
totypes of thymoma, p=0.650. PFS was predicted by R0 resection in all histotypes
and by the Masaoka–Koga stage in the type B2 subgroup.
Conclusion: Combining the two staging methods to guide the diagnosis and treat-
ment of patients with B2 +B3 thymoma is recommended. R0 resection is recom-
mended to reduce recurrence. Patients with B2 +B3 thymoma have a prognosis
similar to those with a B2 thymoma or a B3 thymoma alone.
KEYWORDS
prognosis, real-world study, thymoma, treatment, type B2 +B3
INTRODUCTION
The World Health Organization (WHO) updated its histo-
logical classification of thymomas, a rare malignancy and
the most common mediastinal tumors,
1
in 2021.
2,3
Based on
the morphological features of epithelial tumor cells, the per-
centage of the nontumoral lymphocytic component, and the
degree to which the tumor resembles normal thymic archi-
tecture, thymomas are further classified into subtypes (A,
AB, B1, B2, and B3).
2,4
Given the prevalence of thymomas with various histo-
logical features, a subtype of thymoma known as combined
thymomas was previously recognized but later abandoned
in 2014.
2
Similar to the Gleason scale, International Thymic
Malignancy Interest Group recommended that all tumor
subtypes be listed in order of predominance when making a
diagnosis; minor components should be reported in 10%
increments, and thymoma components of 0% to 10% can be
neglected.
2
Some borderline cases can be mixed in any pro-
portion of type B2 and B3 thymoma, which should be
Received: 20 February 2023 Accepted: 16 March 2023
DOI: 10.1111/1759-7714.14875
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium,
provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Thorac Cancer. 2023;14:1339–1347. wileyonlinelibrary.com/journal/tca 1339
reported as type B2 +B3 thymoma (i.e., more than 10% of
both components) rather than as type B2 or B3 thymoma
due to a morphological continuum between the two
subtypes.
2,4
In clinical practice, we found that many patients have been
diagnosed with type B2 +B3 thymoma. However, the clinical
characteristics, treatment outcomes, and prognosis of these
patients have rarely discussed in previously published studies.
5
For this reason, we aimed to summarize the management
experience of patients with type B2 +B3 thymoma by review-
ing the information of those who were diagnosed with this
tumor at our hospital over the past decade and comparing it to
that of patients with type B2 and B3 thymoma.
METHODS
Ethics statement
This publication was approved by the Institutional Review
Board (IRB) of Peking Union Medical College Hospital
(PUMCH) on December 8, 2022. ID number of the IRB is
K22C2462. The patient’s informed consent was waived by
the IRB.
Patient characteristics
A total of 245 patients were diagnosed with type B2 thy-
moma, type B3 thymoma, or type B2 +B3 thymoma
between January 2012 and December 2021 at the PUMCH,
Chinese Academy of Medical Science and Peking Union
Medical College. During this period, 41 patients were diag-
nosed with type B2 +B3, 137 patients with type B2, and
67 with type B3. A total of nine patients (2 cases of type
B2 +B3, 3 cases of type B3, and 4 cases of type B2) were
excluded from the study because of intraoperative death or
no definite stage recorded. Finally, the data from 236 patients
were retrospectively analyzed.
Diagnosis and treatment
All patients were pathologically confirmed via surgery or
needle biopsy. The pathological diagnosis of all patients
(including biopsy samples) was reviewed by professional
pathologists and meets the 2021 WHO diagnostic criteria.
The stage of thymoma was classified based on the tumor,
node, metastasis (TNM) staging system and with reference
to the Masaoka–Koga staging system.
6,7
The lymph nodes of
all patients undergoing surgery were evaluated pathologi-
cally to determine the TNM stage. The patients included in
the study received at least one treatment at our hospital,
including surgery, chemotherapy, radiotherapy, immuno-
therapy, or ablation. Recurrence or metastases was con-
firmed via chest and abdominal computed tomography as
well as positron emission tomography.
Follow-up and statistical analysis
The patients were followed up every 6 months after the
completion of the treatment in the initial 5 years and every
12 months thereafter. The duration of progression-free sur-
vival (PFS) was calculated from the date of operation until
the detection of disease progression for patients who had
stable disease after the initial treatment. A total of six
patients died during this study. Because this number was
very small, we set the primary endpoint of the study as dis-
ease progression, indicated by a recurrence or metastasis of
the tumors.
Descriptive statistics are reported as the mean, range,
and standard deviation of continuous variables and as the
frequency and proportion of categorical variables. The t-test
was applied to compare the difference between the mean
values of continuous variables, and the χ
2
test and Fisher’s
exact test were employed to compare the difference between
the proportions of categorical variables. The Kaplan–Meier
method was employed to estimate the PFS for the entire
cohort as well as to perform univariate analysis for the
assessment of prognostic factors. Univariate and multivari-
ate analyses were performed using the Cox regression
model. Statistical analysis was performed using SPSS 26.0
and GraphPad Prism 9.
RESULTS
Characteristics
The study included a total of 236 patients, but we were
unable to obtain complete information due to a loss of
follow-up in 13 patients. Table 1and Figure 1illustrate the
most salient clinical characteristics of the patients analyzed
in this study. Of all patients, 41.9% had myasthenia gravis
(MG), with type B3 patients having a significantly lower
prevalence of MG compared to type B2 and type B2 +B3
patients (p=0.038 and p=0.028, respectively). Moreover,
four patients developed additional paraneoplastic diseases,
including one case each of primary thrombocytosis, Sjog-
ren’s syndrome, psoriasis, and autoimmune encephalitis.
TNM staging system showed a linear increase in the per-
centage of patients at an advanced stage across the three his-
totypes of B2, B2 +B3, and B3 with respective rates of
19.5%, 25.6%, and 35.9%, respectively, p=0.045. Contrary
to expectations, Masaoka–Koga staging system did not
reveal any such variation.
Treatment and outcome
The median time patients were followed up was for
60 months (1–128 months). Table 2provides extensive visu-
alization of the patients’treatment and development. A total
of 77 patients (32.6%) underwent open surgery, including
69 cases (29.2%) of sternotomy. A total of 146 patients
1340 ZHAO ET AL.
(61.9%) underwent minimally invasive surgery, including
144 cases (61.0%) video-assisted thoracoscopic surgery and
two cases of subxiphoid surgery. A total of eight patients
failed to receive surgery. A total of six patients died during
follow-up. Three patients died from thymoma recurrence or
metastasis of their thymoma, and three others died of unre-
lated causes while under follow-up. Following initial treat-
ment, 23 patients experienced progression, and four
experienced a second progression. Treatments such as
radiotherapy,
2
chemotherapy,
1
and ablation
1
were given to
TABLE 1 The characteristics of the study subjects.
Variables Total Type B2 Type B2 +B3 Type B3
Gender
Male 137 (58.1%) 77 (57.9%) 23 (59.0%) 37 (57.8%)
Female 99 (41.9%) 56 (42.1%) 16 (41.0%) 27 (42.2%)
Age (years)
Average 48.7 (±12.8) 47.1 (±12.8) 49.7 (±11.8) 51.3 (±12.9)
Myasthenia gravis 99 (41.9%) 60 (45.1%) 20 (51.2%) 19 (29.6%)
TNM stage
I+II 177 (75.0%) 107 (80.5%) 29 (74.4%) 41 (64.1%)
III +IV 59 (25.0%) 26 (19.5%) 10 (25.6%) 23 (35.9%)
Masaoka–Koga stage
I+II 150 (63.6%) 92 (69.2%) 22 (56.4%) 36 (56.3%)
III +IV 86 (36.4%) 41 (30.8%) 17 (43.6%) 28 (43.7%)
Tumor size
<6 cm 152 (64.4%) 85 (63.9%) 23 (59.0%) 44 (68.8%)
≥6 cm 84 (35.6%) 48 (36.1%) 16 (41.0%) 20 (31.2%)
Smoking 131.6 (±305.9) 131.9 (±311.1) 117.9 (±271.6) 139.4 (±318.8)
Tumor invasion
Yes 89 (37.7%) 45 (33.8%) 17 (43.6%) 27 (42.2%)
No 147 (62.3%) 88 (66.2%) 22 (56.4%) 37 (57.8%)
FIGURE 1 Stage distribution of thymoma histotypes. The stage classification is based on the tumor, node, metastasis (TNM) staging system (a +b) and
Masaoka–Koga staging system (c +d).
ZHAO ET AL.1341
patients who had experienced a second progression. The
median PFS of patients received chemotherapy (both pre-
and postoperatively) was 68.0 months. The chemotherapy
group has a lower recurrence rate than the nonchemother-
apy group (22.9% vs. 45.0%), p=0.087.
Prognosis and prognostic factors
Chi-square and Fisher’s exact tests were used to assess the
impact of gender, age, TNM stage, Masaoka–Koga stage, R0
resection, tumor size, radiotherapy, MG, tumor invasion,
smoking, and histotype on PFS (Figures 2and 3). The prog-
nosis of patients with early-stage, noninvasive and R0
resected tumors was better, p< 0.001, and the prognosis of
tumors larger than 6 cm was worse, p=0.027. Table 3
shows the subgroup analysis results of each pathological
type. Except for MG, the above factors were included in the
multivariate analyses (Table 4). In the univariate analyses,
the TNM stage, Masaoka–Koga stage, R0 resection, and
tumor invasion were predictive of PFS in total and all
histotypes. In addition, age and smoking were predictive of
PFS in the type B2 subgroup; tumor size was predictive of
PFS in all patients. In the multivariate analysis of all
patients, age, R0 resection, and Masaoka–Koga stage were
significantly predictive of PFS. In subgroup analyses, R0 re-
section was predictive of PFS in all histotypes, and the
Masaoka–Koga stage was predictive of PFS in the type B2
subgroup.
DISCUSSION
So far as we are aware, this is the first report to examine the
clinicopathological characteristics, treatment, and prognosis
of patients with type B2 +B3 thymoma.
In this study, we found that the clinical characteristics of
type B2 +B3 thymomas were not statistically different from
those of type B2 or B3 thymomas. This included patient
gender, average age, Masaoka–Koga stage, tumor size, smok-
ing status, tumor invasion, and the proportion of patients
with MG (Table 1). Patients with type B2 or B3 thymoma,
whose median age ranged from 51 to 54 years old, be not
more likely to be male or female in previous large-scale ret-
rospective studies.
5,8,9
Patients in this study, however, ran-
ged in age between 47.1–51.3 years old and had a higher
proportion of men (skewed male, 57.8%–59.0%).
However, we did find significant differences in some
areas. Based on these two classifications of staging system,
we classify stages I and II as early-stage and stages III and
IV as an advanced-stage in the two staging systems. Consis-
tent with the conclusion of Meurgey et al.,
10
we found that
the percentage of patients with TNM advanced stage B2
(19.5%), B2 +B3 (25.6%), and B3 (35.9%) increased gradu-
ally over time (p=0.045). Similarly, there was a statistically
significant difference between the R0 resection rate of the
three subgroups (p=0.005) (i.e., more patients with early-
stage mean higher R0 resection rate) with the B2 group
TABLE 2 Treatment and progression of the study patients.
Variables Total Type B2 Type B2 +B3 Type B3
Residual disease
R0 217 (91.9%) 128 (96.2%) 36 (92.3%) 53 (82.8%)
R1/R2 7 (3.0%) 1 (0.8%) 1 (2.6%) 5 (7.8%)
Progression
Yes 23 (9.7%) 12 (9.0%) 4 (10.3%) 7 (10.9%)
No 203 (86.0%) 113 (85.0%) 34 (87.2%) 56 (87.5%)
Postoperative therapy
Radiotherapy 107 (45.3%) 54 (40.6%) 17 (43.6%) 36 (56.3%)
Chemotherapy 14 (5.9%) 3 (2.3%) 6 (15.4%) 5 (7.8%)
Concurrent chemoradiation 2 (0.8%) 1 (0.8%) 1 (2.6%) 0 (0.0%)
Chemotherapy +radiotherapy 7 (3.0%) 0 (0.0%) 2 (5.1%) 5 (7.8%)
Radiotherapy +chemotherapy 9 (3.8%) 3 (2.3%) 1 (2.6%) 5 (7.8%)
None 85 (36.0%) 62 (46.6%) 11 (28.2%) 12 (18.8%)
FIGURE 2 Kaplan–Meier curve for progression-free survival (PFS)
according to the histotype, p=0.650.
1342 ZHAO ET AL.
having the highest R0 resection rate (96.2%), and the B3
group having the lowest R0 resection rate (82.8%). The
Masaoka–Koga staging system, on the other hand, showed
no such variation. Our findings are partially consistent with
previous reports that found no correlation between WHO
type and stage (either TNM or Masaoka–Koga) in patients
with type B thymoma.
8,11
However, neither addressed the
specific stage at which the patients with type B2 +B3 thy-
moma presented. Therefore, we can conclude that type B2
+B3 thymoma can be thought of as intermediate between
type B2 and type B3 thymomas, and the number of patients
with these TNM advanced-stage thymomas is gradually
increasing. In our opinion, R0 resection should be guided
more by the TNM stage.
Several studies have found that the MG rate for type B2
thymoma ranged from 19% to 49%,
8,11
while for type B3
thymoma it was 30.5% to 40%.
8,12
The percentages found in
our study, 45.1% and 29.6%, are comparable to those of
other large-scale studies.
8,11,12
In our research, the MG rate
of type B2 +B3 thymoma was the highest of the three sub-
groups, at 51.2%. This rate was not intermediate between
that of type B2 and type B3 thymoma. There was no statisti-
cally significant difference in MG incidence between the
groups. Thus, we hypothesized that B2, B2 +B3, and B3
thymoma histotypes are unrelated to MG.
Due to the rarity of thymoma, at present there is no
standard treatment protocol. It is typically believed that sur-
gery is the main treatment method, while the selection of
supplementary treatment methods is individualized.
13
Cur-
rently, radiotherapy is the common choice of adjuvant care,
and oftentimes the only option after surgery has failed. Ret-
rospective studies have shown a positive association between
postoperative radiotherapy (PORT) and increased overall
survival (OS), with the greatest relative benefits seen in
patients with Masaoka–Koga stage IIB to IV disease or non-
complete resection.
12,14,15
Similar to our results ( p=0.237),
Kim et al.
16
and Gao et al.
12
observed that the PORT did not
affect PFS in patients with type B thymomas, even in the
patients with advanced-stage, p=0.484 (TNM staging sys-
tem), p=0.784 (Masaoka–Koga staging system). We believe
that there are two possible hypotheses for explaining this
phenomenon. The first thing to note is that as much as 28%
of patients in the study by Lim et al.
14
had non-R0 resec-
tions. As a surgical adjunct, PORT can help these patients’
conditions be managed more effectively, leading to
improved outcomes after surgery. Since the majority of
patients in this study underwent R0 resection (92%), the
effect of PORT is likely obscured or masked by R0 resection.
Furthermore, patients typically require additional treatment
after disease progression, so the benefit of OS may come
from comprehensive treatment. Although, more systematic
large-scale studies are needed to confirm this hypothesis.
Due to the lack of large-scale randomized controlled
studies, the importance of chemotherapy for thymoma is
still uncertain, but it may be proposed for advanced stages
or recurrent thymic tumors.
17,18
Although there is no
FIGURE 3 Kaplan–Meier curve for progression-free survival (PFS) according to the TNM stage (a), p< 0.001; Kaplan–Meier curve for the PFS
according to Masaoka–Koga stage (b), p< 0.001; Kaplan–Meier curve for the PFS according to R0 resection (c), p< 0.001; Kaplan–Meier curve for the PFS
according to tumor invasion (d), p< 0.001.
ZHAO ET AL.1343
standard chemotherapy option, when deciding on first-line
chemotherapy for thymoma, the data suggest that either
cisplatin-anthracycline or cisplatin-etoposide is the best
option, with response rates averaging between 17% and
50%. This finding holds regardless of the treatment line or
histological type (thymoma vs. thymic carcinoma).
18,19
According to Ma et al.,
20
patients with advanced thymoma
or thymic carcinoma may have similar long-term PFS and
OS following different first-line chemotherapy regimens cis-
platin, doxorubicin, and cyclophosphamide (CAP); cisplatin
TABLE 3 Chi-square test and Fisher’s exact test results of the progression-free survival (PFS) (subgroup analysis).
Variables B2 p-value B2 +B3 p-value B3 p-value
Gender 0.239 0.286 0.223
Male 9 (11.7%) 1 (4.3%) 6 (16.2%)
Female 3 (5.4%) 3 (18.8%) 1 (3.7%)
Age (years) 0.014 >0.999 >0.999
<50 11 (14.3%) 2 (11.1%) 3 (11.1%)
≥50 1 (1.8%) 2 (9.5%) 4 (10.8%)
TNM stage 0.005 0.003 <0.001
I+II 6 (5.6%) 0 (0.0%) 0 (0.0%)
III IV 6 (23.1%) 4 (40.0%) 7 (30.4%)
M–K stage <0.001 0.016 0.001
I+II 2 (2.2%) 0 (0.0%) 0 (0.0%)
III +IV 10 (24.4%) 4 (23.5%) 7 (25.0%)
R0 resection 0.005 <0.001 <0.001
Yes 9 (7.0%) 1 (2.8%) 1 (1.9%)
No 3 (60.0%) 3 (100.0%) 6 (54.5%)
Tumor size 0.093 >0.999 0.191
≥6 cm 7 (14.6%) 2 (12.5%) 4 (20.0%)
<6 cm 5 (5.9%) 2 (8.7%) 3 (6.8%)
Radiotherapy 0.231 0.919 0.678
Yes 8 (13.6%) 2 (9.5%) 6 (13.0%)
No 4 (6.0%) 2 (11.8%) 1 (5.9%)
MG 0.801 0.605 0.664
Yes 5 (8.3%) 3 (15.0%) 1 (5.3%)
No 7 (9.6%) 1 (5.3%) 6 (13.3%)
Tumor invasion 0.002 0.037 0.001
Yes 10 (20.5%) 4 (22.2%) 7 (25.9%)
No 2 (3.4%) 0 (0.0%) 0 (0.0%)
Smoking 0.025 0.556 0.370
Yes 7 (17.5%) 0 (0.0%) 3 (17.6%)
No 5 (5.4%) 4 (13.8%) 4 (8.5%)
Abbreviations: MG, myasthenia gravis; MK, Masaoka–Koga stage.
TABLE 4 Multivariate analyses of the progression-free survival (PFS).
Type Variables Hazard ratio PFS 95% confidence interval p-value
Total Age (years) 0.955 0.922–0.990 0.011
R0 eesection 14.766 5.591–38.998 <0.001
MK stage 10.273 2.285–46.183 0.002
B2 MK stage 9.209 1.954–43.395 0.005
R0 resection 15.795 3.565–69.990 <0.001
B2 +B3 R0 resection 44.951 4.649–434.644 0.001
B3 R0 resection 37.993 4.538–318.085 0.001
Abbreviation: MK, Masaoka–Koga stage.
1344 ZHAO ET AL.
and etoposide; and cisplatin and paclitaxel (TP). After che-
motherapy, the median PFS was 18.0–34.5 months for
patients with Masaoka–Koga stages III and IVA disease, and
the 5-year OS rate was 60.0% to 84.9%; for with Masaoka–
Koga stage IVB disease, the median PFS was 8.2–
11.6 months, and the 5-year OS rate was 14.3% to 41.1%.
20
In this series, 34 patients received chemotherapy (both
pre- and postoperatively), with four patients receiving the
cisplatin, doxorubicin, vincristine, and CAP protocol,
14 patients receiving the TP protocol, 12 patients receiving
the CAP protocol, and four patients receiving other proto-
cols. The main purpose of patients receiving induction ther-
apy is to increase the possibility of R0 resection. The median
PFS of them was 68.0 months; the reason for this difference
may be that 32.4% of patients receiving chemotherapy in
our study were classified into Masaoka–Koga stage
II. Although the chemotherapy group has a lower recurrence
rate than the non-chemotherapy group (22.9% vs. 45.0%),
the difference was not statistically significant ( p=0.087).
Our result showed that the difference was also absent if R0 re-
section is selected for advanced patients (11.1% vs. 18.2%,
p=0.517), which was confirmed via previous research.
11,19
However, the possibility that resection status plays a function
in recurrence is not negated by this result. Our results do not
support chemotherapy for type B2, B2 +B3, and B3 thy-
moma patients based on R0 resection, and it is both unrea-
sonable and inefficient to carry out clinical trials of adjuvant
chemotherapy on them. Additionally, immunotherapy and
targeted therapy are rarely used, only in a few case reports
and small-scale phase II studies
21–24
to back them.
Based on our findings, R0 resection may have an impact
on the PFS of patients who have type B2 +B3 thymoma
(Table 4). Patients with B2 +B3 thymoma did not have a
significantly worse PFS compared to those with B2 or B3
thymoma alone. The most significant factors affecting pro-
gression across all patients studied were R0 resection,
Masaoka–Koga stage, and age. Previous research has sug-
gested that in order to achieve an 80% test efficiency for the
three moderate effect factors, at least 75 patients would need
to be tested.
25
Thus, it is important to proceed with caution
when interpreting the study’s findings regarding the prog-
nostic factors of each pathological subgroup. Although pre-
vious studies have shown that pathological subtypes have an
impact on the prognosis of patients, it is generally believed
that there is no difference in the prognosis between B2 and
B3 pathological subtypes.
5,8,26
Our study’s finding that PFS
is unaffected by pathological subtypes suggests that the
prognosis of patients with these three subtypes can be com-
pared without further subgroup analysis.
There is some debate in the literature about whether or
not R0 resection has any prognostic value. Most studies
agree that R0 resection is one of the most independent prog-
nostic factors for thymoma,
8,11–13,26
whether OS or PFS.
However, some reports have shown that there was no sur-
vival difference for patients who underwent complete re-
section compared with the patients undergoing incomplete
resection.
27
Despite the small sample size, our results favor
the former conclusion. In our study, we found that applying
some induction therapy before surgery increased the likeli-
hood of R0 resection for four patients who underwent it; of
these four, three did not experience a recurrence or metasta-
sis during the follow-up period.
The Masaoka–Koga stage is another critical prognostic
factor in our analysis. PFS was significantly lower in the
Masaoka–Koga advanced stage group in both univariate
analysis and multivariate analysis (Table 4, Figure 3b). The
Masaoka–Koga stage and TNM stage are well-established as
independent prognostic factors for thymomas of all
types,
8,10,28
and this is confirmed by studies on type B2 and
B3 thymoma.
11,12,16
In our study, the Masaoka–Koga stage
and TNM stage were both found to have a significant
impact on PFS in univariate analysis (Figure 3ab), but only
the Masaoka–Koga stage was found to have a prognostic sig-
nificance in multivariate analysis (Table 4). Therefore, we
believe that the Masaoka–Koga staging system is a better
prognostic indicator than the TNM staging system in type
B2 +B3, type B2, and type B3 thymomas.
Since the tumor diameter is not a part of the Masaoka–
Koga or TNM staging system for thymomas, as it is for
other solid tumors,
5,6
researchers have also evaluated the
effect this may have on prognosis. In this context, some
studies pointed out smaller tumor size was associated with
better survival in thymoma patients, showing its potential as
an independent prognostic factor.
13,29
Recent meta-analyses,
however, have shown that tumor size is not a reliable prog-
nostic indicator.
5,9,28
Our findings lend credence to the latter
theory, that is, tumor size is irrelevant to the prognosis of
patients with thymoma of type B2, B3, and B2 +B3.
However, we do not consider our results to be conclu-
sive, and we still have several major issues to address. In the
first place, our study had a major flaw because the patient’s
care was not coordinated with a prospective institutional
treatment protocol. Second, it is limited by its retrospective
design. In addition, the sensitivity of fine needle aspiration
cytology for thymoma was 87%, and its specificity was 94%.
30
Our study’s important conclusion was influenced by the fact
that fine needle aspiration cytology was used to establish the
pathological diagnosis in nine patients. Further, although
patients with advanced thymomas received adjuvant treat-
ment, there was no uniformity in the indications for adjuvant
therapy, which may have affected the outcomes. Finally,
although the mathematical model of the statistical analysis
package could take the short follow-up time of some patients
into consideration, the conclusions may still be biased and
should be interpreted with caution. All these concerns should
be further investigated in future prospective clinical trials.
ACKNOWLEDGMENTS
This work was supported by the National High Level Hospi-
tal Clinical Research Funding (2022-PUMCH-B-011) and
(2022-PUMCH-B-012). The authors would like to thank
Yushang Cui MD, Zhijun Han MD, Li Li MD, Naixin Liang
MD, Yingzhi Qin MD for contribution of the treatment for
patients in this study. The authors would like to thank all
ZHAO ET AL.1345
the reviewers who participated in the review and MJEditor
(www.mjeditor.com) for its linguistic assistance during the
preparation of this manuscript.
AUTHOR CONTRIBUTION
All authors had full access to the data in the study and take
responsibility for the integrity of the data and the accuracy
of the data analysis. Conceptualization: Ke Zhao, Yeye Chen,
Lei Liu and Jiaqi Zhang. Data curation: Ke Zhao, Xuehan
Gao and Ke Rao. Formal analysis: Ke Zhao, Mengxin Zhou
and Libing Yang. Investigation: Ke Zhao and Ke Rao. Visu-
alization: Ke Zhao, Guige Wang and Mengxin Zhou.
Writing–original draft preparation: Ke Zhao and Mengxin
Zhou. Project administration: Yeye Chen, Hongsheng Liu
and Shanqing Li. Resources: Yeye Chen, Chao Guo, Ye
Zhang and Cheng Huang. Supervision: Yeye Chen, Hon-
gsheng Liu and Shanqing Li. Writing–review and editing:
Yeye Chen. Funding acquisition: Shanqing Li.
CONFLICT OF INTEREST STATEMENT
The authors declare no interest conflict of interest.
ORCID
Ke Zhao https://orcid.org/0000-0001-7910-2453
Yeye Chen https://orcid.org/0000-0001-6654-7701
Jiaqi Zhang https://orcid.org/0000-0001-7798-3816
Xuehan Gao https://orcid.org/0000-0003-4841-570X
Chao Guo https://orcid.org/0000-0003-2170-5096
Shanqing Li https://orcid.org/0000-0003-2437-1108
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How to cite this article: Zhao K, Chen Y, Liu L,
Wang G, Zhang J, Zhou M, et al. Real-world study of
treatment and outcome of type B2 +B3 thymoma:
The neglected part of thymoma. Thorac Cancer.
2023;14(15):1339–47. https://doi.org/10.1111/1759-
7714.14875
ZHAO ET AL.1347
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