Introduction
Hepatocellular carcinoma (HCC) ranks third among the
leading causes of cancer-related mortality worldwide (1,2). It
has been reported that >50% of patients with HCC are diagnosed
at an advanced stage due to the asymptomatic nature of early
disease, thereby missing the optimal window for radical surgery
intervention. Patients with advanced-stage HCC are now generally
treated with systemic therapy, which combines immune checkpoint
inhibitor (ICI) with molecularly targeted drugs. According to the
findings of IMbravel150, ORIENT-32 and CARES-310, programmed cell
death protein-1 (PD-1) inhibitors, programmed death-ligand 1
(PD-L1) inhibitors and cytotoxic T lymphocyte-associated antigen-4
inhibitors are the three main classes of ICIs (3–6).
Molecularly targeted drugs include tyrosine kinase inhibitors
(TKIs) and vascular endothelial growth factor receptor antagonists.
PD-1 inhibitors combined with TKIs have markedly improved
prognostic outcomes in several advanced malignancies, including
HCC, renal cell carcinoma and non-small cell lung cancer. In
addition to their antitumor effects, these therapies also have been
associated with immune-related adverse events affecting multiple
organ systems in the body, particularly the endocrine systems. The
most common endocrine adverse event is thyroid dysfunction (TD)
(7,8).
Previous research has indicated that elevated TSH
receptor expression is associated with poor prognosis in patients
with HCC (9). Thyroid hormones
serve a key role in regulating the proliferation and
differentiation of HCC (10).
Thyroxine facilitates the proliferation of cancer stem-like cells
and enhances resistance to in vitro treatments, thereby
accelerating tumor growth in patients with HCC (11). Previous studies have reported that,
compared with patients without TD, patients with solid tumors such
as melanoma and non-small cell lung cancer, who developed TD after
ICI therapy, exhibit prolonged overall survival (OS) and
progression-free survival (PFS) (12–14). A
2022 study that enrolled 74 patients with HCC undergoing PD-1
inhibitor-based combination therapy set PFS as the primary outcome.
The results demonstrated that patients with hypothyroidism had a
longer PFS (7.44 months) compared with patients without
hypothyroidism (5.68 months). However, this study did not further
explore the association between sex and PD-1 inhibitor-related
hypothyroidism (15) The female sex
is a well-recognized risk factor for the occurrence of autoimmune
thyroid disorders, such as Graves' and Hashimoto's thyroiditis with
a female-to-male ratio of 8:1 (16–19).
The association of the female sex with TKIs-associated
hypothyroidism suggests an underlying immune mechanism. Previous
studies have also indicated that TD is more prevalent in female
patients with cancer treated with TKIs (20,21).
Thus, female patients with HCC were excluded from the present study
to minimize the influence of potential confounding factors.
The aim of the present study was to assess whether
hypothyroidism induced by TKIs and PD-1 inhibitors are associated
with favorable clinical outcomes in male patients with HCC.
Patients and methods
Study population
A retrospective analysis was conducted on male
patients with HCC who received PD-1 inhibitors combined with TKI
therapy at Nanjing Second Hospital (Nanjing, China) from July 2020
to August 2024. The inclusion criteria were as follows: i) Male
patients confirmed with HCC who received anti-PD-1 drugs combined
with TKI drugs; ii) completion of at least two cycles of standard
anti-PD-1 therapy combined with TKI drugs; and iii) normal thyroid
function prior to treatment. Exclusion criteria were as follows: i)
Metastatic liver cancer or malignant bile duct tumors; ii)
incomplete imaging data or lack of thyroid function records before
and after treatment; and iii) female patients with HCC. PD-1
inhibitors included sintilimab (cat. no. S20180016; Innovent
Biologics, Inc.) and tislelizumab (cat. no. S20190045; BeiGene,
Ltd.), both administered intravenously at a fixed dose of 200 mg
every 3 weeks. For TKIs, sorafenib (cat. no. H20160201; Bayer
Schering Pharma; Bayer AG) was administered orally at a dosage of
400 mg daily, while lenvatinib (cat. no. H20180052; Eisai Co.,
Ltd.) was administered orally dosed at 8–12 mg/day based on the
body weight of the patient. The present study was approved by the
Ethics Committee of Nanjing Second Hospital (approval no.
2024-LS-ky-098; Nanjing, China).
Data collection
Baseline clinical data were collected from enrolled
patients, including age, body mass index (BMI), Child-Pugh
classification (22) and history of
previous therapy. Furthermore, the present study collected relevant
indicators such as peripheral blood biochemistry, complete blood
count, α-fetoprotein (AFP) and thyroid-related hormones.
Diagnostic criteria
Chemiluminescent immunoassay was used to measure
thyroid function parameters. Free triiodothyronine (FT3) and free
thyroxine (FT4) have normal ranges of 2.43–6.01 pmol/l and
9.01–19.05 pmol/l, respectively. The normal range for
thyroid-stimulating hormone (TSH) is 0.35–4.94 mIU/l. The normal
range for thyroglobulin antibody (TgAb) is 0–150 IU/ml. The normal
range for thyroid peroxidase antibody (TPOAb) is 0–34 IU/ml. TD was
classified into four subtypes based on the recommendation of the
American Thyroid Association (23):
i) Overt hyperthyroidism: Elevated FT4 or FT3 with decreased TSH;
ii) subclinical hyperthyroidism: Normal FT4 and FT3 levels with
decreased TSH; iii) overt hypothyroidism: Decreased FT4 or FT3 with
elevated TSH; and iv) subclinical hypothyroidism: Normal FT4 and
FT3 levels with elevated TSH.
Patient grouping
Patients were divided into two groups based on the
first occurrence of TD during treatment: The hypothyroidism group
(n=36) and the normal thyroid function group (n=41). The
hypothyroidism group comprised two subgroups: Overt and subclinical
hypothyroidism.
Statistical analysis
Data were analyzed using SPSS statistical software
(version 27.0; IBM Corp.). Normally distributed data were presented
as the mean ± standard deviation (SD) and analyzed using unpaired
t-tests, while non-normally distributed data were presented as the
median (interquartile range) and analyzed using the Wilcoxon
rank-sum test. Bonferroni correction was applied following ANOVA.
Count data were presented as n (%). Intergroup comparisons were
performed using χ2 and Fisher's exact tests. Sensitivity
analysis was conducted to validate the robustness of the results.
Univariate and multivariate Cox proportional hazards regression
analyses were performed to identify independent prognostic factors,
with PFS as the primary outcome. P<0.05 was considered to
indicate a statistically significant difference.
Results
Baseline characteristics of the two
groups
A total of 77 male patients with HCC were included
in the present study, selected from 406 patients with HCC who
received anti-PD-1 plus TKI therapy between July 2020 and August
2024 (Table I). The median age was
59.2 years (range, 28–81 years). Prior to treatment initiation, 72
(93.5%), 41 (53.2%) and 6 (7.8%) had received transarterial
chemoembolization, microwave ablation or curative surgery,
respectively (Table I). Enrolled
patients received different PD-1 inhibitors and TKIs, and detailed
information is provided in Table
I.
 | Table I.Baseline characteristics of 77 male
patients with HCC. |
Table I.
Baseline characteristics of 77 male
patients with HCC.
|
Characteristics | Normal thyroid
function group (n=41) | Hypothyroidism
group (n=36) | P-value |
|---|
| Age (years), n
(%) |
|
| 0.726 |
|
<60 | 20 (48.8) | 19 (52.8) |
|
|
≥60 | 21 (51.2) | 17 (47.2) |
|
| BMI, n (%) |
|
| 0.940 |
|
≤24.9 | 27 (65.9) | 24 (66.7) |
|
|
>24.9 | 14 (34.1) | 12 (33.3) |
|
| Type 2 diabetes, n
(%) |
|
| 0.951 |
| No | 31 (75.6) | 27 (75.0) |
|
|
Yes | 10 (24.4) | 9 (25.0) |
|
| Hypertension, n
(%) |
|
| 0.966 |
| No | 26 (63.4) | 23 (63.9) |
|
|
Yes | 15 (36.6) | 13 (36.1) |
|
| Prior TACE, n
(%) |
|
| 0.364 |
| No | 4 (9.8) | 1 (2.8) |
|
|
Yes | 37 (90.2) | 35 (97.2) |
|
| Prior microwave
ablation, n (%) |
|
| 0.593 |
| No | 18 (43.9) | 18 (50.0) |
|
|
Yes | 23 (56.1) | 18 (50.0) |
|
| Prior operation, n
(%) |
|
| >0.999 |
| No | 38 (92.7) | 33 (91.7) |
|
|
Yes | 3 (7.3) | 3 (8.3) |
|
| Child-Pugh, n
(%) |
|
| 0.508 |
| A | 27 (65.9) | 27 (75.0) |
|
| B or
C | 14 (34.1) | 9 (25.0) |
|
| BCLC, n (%) |
|
| 0.438 |
| A | 5 (12.2) | 3 (8.3) |
|
| B or
C | 36 (87.8) | 33 (91.7) |
|
| AFP (ng/ml), n
(%) |
|
| 0.683 |
|
≤200 | 28 (68.3) | 23 (63.9) |
|
|
>200 | 13 (31.7) | 13 (36.1) |
|
| PD-1 inhibitors, n
(%) |
|
| 0.321 |
|
Nivolumab | 24 (58.5) | 17 (47.2) |
|
|
Tislelizumab | 17 (41.5) | 19 (52.8) |
|
| TKIs, n (%) |
|
| 0.857 |
|
Sorafenib | 27 (65.9) | 23 (63.9) |
|
|
Lenvatinib | 14 (34.1) | 13 (36.1) |
|
| FT3, pmol/l (95%
CI) | 3.0 (2.5–4.0) | 3.5 (2.5–4.5) | 0.292 |
| FT4, pmol/l (95%
CI) | 12.4±2.1 | 12.5±1.9 | 0.676 |
| TSH, mIU/l (95%
CI) | 1.7 (1.2–3.1) | 4.2 (2.0–4.6) |
<0.001a |
| TPOAb, IU/ml (95%
CI) | 0.8 (0.5–5.5) | 7.0 (2.0–22.5) | 0.003a |
| TGAb, IU/ml (95%
CI) | 1.4 (0.8–5.0) | 12.4
(2.1–18.2) | 0.007a |
| PFS, months (95%
CI) | 6.1 (3.1–6.7) | 8.0 (6.0–12.1) |
<0.001a |
| OS, months (95%
CI) | 11.2
(6.5–18.7) | 16.3
(7.8–20.4) | 0.168 |
36 patients developed hypothyroidism during
treatment, among whom 6 initially presented with transient
hyperthyroidism following systemic treatment. All 6 patients
eventually progressed to hypothyroidism and none received
pharmacological treatment. By the end of follow-up (April 2025), no
enrolled patients had died from serious drug-related adverse events
(such as grade 3 diarrhea, immune-related hepatitis and severe skin
toxicity).
Comparison of baseline thyroid hormone
levels between two groups
No significant differences in baseline FT3 and FT4
levels were observed between the normal thyroid function and the
hypothyroidism groups [3.0 pmol/l; 95% confidence interval (CI),
2.5–4.0 pmol/l] vs. 3.5 pmol/l (95% CI, 2.5–4.5 pmol/l); P=0.292]
and (12.4±2.1 pmol/l vs. 12.5±1.9 pmol/l; P=0.676), respectively
(Table I).
Significant differences in baseline TSH levels were
detected between the two groups. Baseline serum TSH levels were
significantly higher in the hypothyroidism group [4.2 mIU/l (95%
CI, 2.0–4.6 mIU/l)] compared with that in the normal thyroid
function group [1.7 mIU/l (95% CI, 1.2–3.1 mIU/l)] (P<0.001;
Table I).
Additionally, baseline TgAb levels were
significantly higher in the hypothyroidism group [12.4 IU/ml (95%
CI, 2.1–18.2 IU/ml)] compared with the normal thyroid function
group [1.4 IU/ml (95% CI, 0.8–5.0 IU/ml)] (P=0.007; Table I). For the 45 samples with complete
TgAb/TPOAb data, the present study conducted a sensitivity
analysis. The baseline characteristics (age, Child-Pugh class, AFP
level and PFS) of 45 patients with available data were compared and
the results demonstrated that PFS remained the key variable with
statistical significance (P=0.004; Table II).
| Table II.Baseline characteristics of 45 male
patients with HCC with complete TgAb/TPOAb data. |
Table II.
Baseline characteristics of 45 male
patients with HCC with complete TgAb/TPOAb data.
|
Characteristics | Normal thyroid
function group (n=23) | Hypothyroidism
group (n=22) | P-value |
|---|
| Age (years), n
(%) |
|
| 0.894 |
|
<60 | 13 (56.5) | 12 (54.5) |
|
|
≥60 | 10 (43.5) | 10 (45.5) |
|
| Child-Pugh, n
(%) |
|
| 0.912 |
| A | 15 (65.2) | 14 (63.6) |
|
| B or
C | 8 (34.8) | 8 (36.4) |
|
| AFP (ng/ml), n
(%) |
|
| 0.175 |
|
≤200 | 17 (73.9) | 12 (54.5) |
|
|
>200 | 6 (26.1) | 10 (45.5) |
|
| PFS, months (95%
CI) | 6.1 (3.2–6.7) | 8.2 (6.0–12.5) | 0.004a |
Comparative prognosis between two
groups
The hypothyroidism group had a significantly longer
PFS [8.0 months (95% CI, 6.0–12.1 months)] compared with that of
the normal thyroid function group [6.1 months (95% CI, 3.1–6.7
months)] (P<0.001). However, the hypothyroidism group had a
longer OS compared with that of the normal thyroid function group
[16.3 months (95% CI, 7.8–20.4 months) vs. 11.2 months (95% CI,
6.5–18.7 months); P>0.05] (Table
I), the difference was not statistically significant.
In the hypothyroidism group (n=36), 9 patients
achieved complete response (CR; 25%), 6 achieved partial response
(PR; 16.7%), 6 had stable disease (SD; 16.7%) and 15 had
progressive disease (PD; 41.6%). In the normal thyroid function
group (n=41), 4 patients achieved CR (9.8%), 6 achieved PR (14.6%),
10 had SD (24.4%) and 21 had PD (51.2%) (Fig. 1). The hypothyroidism group exhibited
higher objective response rate and disease control rate compared
with that in the normal thyroid function group: 41.7 vs. 24.4% and
58.4 vs. 48.8%, respectively (P=0.170 and P=0.402).
Factors influencing PFS after systemic
therapy
Univariate Cox regression analysis revealed that
hypothyroidism [hazard ratios (HR), 0.317; 95% CI, 0.158–0.637;
P=0.001] was a favorable prognostic factor for male patients with
HCC receiving PD-1 inhibitor plus TKI therapy. By contrast,
baseline serum AFP level >200 ng/ml was an independent adverse
prognostic factor (HR=2.364; 95% CI, 1.283–4.354; P=0.006). The HRs
of developing hypothyroidism after treatment and baseline AFP
levels >200 ng/ml were (HR=0.320; 95% CI, 0.160–0.641; P=0.001)
and (HR=2.354; 95% CI, 1.277–4.340; P=0.006), respectively,
according to the multivariate Cox regression analysis (Table III).
| Table III.Cox regression analysis of factors
associated with PFS in male patients with HCC. |
Table III.
Cox regression analysis of factors
associated with PFS in male patients with HCC.
|
| Univariate
analysis | Multivariate
analysis |
|---|
|
|
|
|
|---|
| Factors | HR (95% CI) | P-value | HR (95% CI) | P-value |
|---|
| Age (≥60 vs. <60
years) | 1.391
(0.883–2.189) | 0.154 | - | - |
| BMI (>24.9 vs.
<24.9) | 0.704
(0.272–1.823) | 0.470 | - | - |
| Prior TACE (yes vs.
no) | 1.577
(0.211–11.796) | 0.657 | - | - |
| Prior microwave
ablation (yes vs. no) | 0.732
(0.308–1.741) | 0.480 | - | - |
| Child-Pugh (B or C
vs. A) | 1.967
(0.818–4.733) | 0.131 | - | - |
| AFP (>200 vs.
≤200 ng/ml) | 2.364
(1.283–4.354) | 0.006a | 2.354
(1.277–4.340) | 0.006a |
| Hypothyroidism (yes
vs. no) | 0.317
(0.158–0.637) | 0.001a | 0.320
(0.160–0.641) | 0.001a |
Comparison of survival curves between
two groups
While there was no statistically significant
difference in the median OS, the median PFS in the hypothyroidism
group was significantly higher compared with that in the normal
thyroid function group (P<0.001). Patients with baseline AFP
>200 ng/ml had significantly shorter median PFS and OS compared
with patients with baseline AFP ≤200 ng/ml (P=0.004 and P=0.004,
respectively; Fig. 2).
Discussion
The present study data demonstrated that male
patients with HCC who developed hypothyroidism following PD-1
inhibitors plus TKI therapy exhibit a longer PFS compared with
those with normal thyroid function. Furthermore, a baseline AFP
level >200 ng/ml prior to treatment serves as an independent
risk factor for both PFS and OS in male patients with HCC.
A previous meta-analysis indicated that TD following
PD-1 inhibitors therapy in patients with solid tumors acts as an
independent factor influencing PFS and OS, with HR of 0.58 and
0.52, respectively (24). The
present study findings were consistent with this observation.
Multivariate Cox regression analysis yielded an HR of 0.320 for
hypothyroidism, suggesting that hypothyroidism is an independent
predictive factor for PFS in patients with HCC. The hypothyroidism
group in the present study comprised both overt and subclinical
cases. Notably, the majority of patients in this group had mild
hypothyroidism, with subclinical hypothyroidism accounting for
66.7% (24/36) of cases, which is consistent with observations from
previous studies (25,26). Due to the limited sample size, the
present study was unable to compare differences in PFS between
these two subgroups. Future prospective multicenter studies are
warranted to evaluate prognostic differences between overt and
subclinical hypothyroidism in patients with HCC treated with PD-1
inhibitors plus TKIs combination therapy. Although the
hypothyroidism group had a longer median OS, the difference was not
statistically significant, which was in line with the findings of a
previous study (27).
In the IMbrave150 study, the incidence of
hypothyroidism among patients with HCC treated with atezolizumab
plus bevacizumab was 10.9%, with a median follow-up of 8.9 months
(28). By contrast, the present
study demonstrated a significantly higher incidence of
hypothyroidism (46.8%). More frequent thyroid function monitoring
and a relatively longer follow-up duration may account for the
higher detection rate of hypothyroidism in the present study. The
small sample size is another potential contributing factor. The
third contributing factor was that all patients received combined
TKI therapy. TKIs induce transient thyrotoxicosis or even permanent
hypothyroidism by damaging thyroid blood vessels and inhibiting
thyroid iodine uptake (20,29). Previous studies have also confirmed
that the use of TKIs in patients with metastatic renal cell
carcinoma is associated with an increased risk of hypothyroidism
(30–32). Whether thyroid injury induced by
TKIs treatment is transient or permanent remains controversial.
After TKIs discontinuation, certain patients recover normal thyroid
function, whereas others persist with hypothyroidism (29).
The present study findings demonstrated that the
baseline TgAb level in the hypothyroidism group was significantly
higher compared with that in the normal thyroid function group. A
retrospective analysis of 316 patients with cancer demonstrated
that 28.48% of TD patients had positive baseline thyroid
autoantibodies (including TgAb), compared with 5.70% of euthyroid
patients (P<0.001) (33).
Another previous study confirmed that abnormal baseline TgAb
significantly elevates the risk of TD (34). ICIs further activate TgAb-specific
autoreactive CD8+ T cells, which infiltrate the thyroid
gland and directly damage thyroid follicular cells, frequently
resulting in a biphasic clinical course of TD (namely, transient
thyrotoxicosis followed by hypothyroidism). The elevated baseline
TSH levels in the hypothyroidism group align with prior findings.
In a retrospective study of 560 ICI-treated patients, baseline TSH
was identified as a strong independent risk factor for TD (odds
ratio, 1.935 per mIU/l; 95% CI, 1.613–2.321; P<0.001) (35). Elevated TSH typically reflects
subclinical thyroiditis or impaired hormone synthesis, which
reduces thyroid resistance to immune-mediated injury. By activating
effector T cells and suppressing regulatory T-cell function, ICIs
disrupt immune tolerance; this enhanced immune activation
preferentially targets thyroid cells with preexisting structural or
functional impairment, accelerating follicular destruction and
overt TD. Notably, higher baseline TSH is specifically associated
with an increased risk of immune-related hypothyroidism. To ensure
early diagnosis and prompt treatment of TD in male patients with
HCC receiving PD-1 inhibitors (with or without TKIs), the present
study findings highlighted the importance of routine baseline
thyroid antibody testing in addition to regular thyroid function
monitoring.
While hypothyroidism is a known side effect of PD-1
inhibitors (36), not all patients
develop this adverse event. Immune-related hypothyroidism may be
driven by increased cytokine levels, stimulation of autoantibody
formation and enhanced T-cell activation (37,38).
Mature CD4+ and CD8+ T cells, B cells and
monocytes frequently express PD-1. By preventing PD-1 from binding
to PD-L1 or -L2, PD-1 inhibitors exert their antitumor activity
(29). Normal thyroid tissue also
expresses the PD-1 ligand. Therefore, cytotoxic T cells may target
the thyroid gland after PD-1 inhibitor administration, impairing
thyroid function. Thyroiditis can also develop when activated
effector T cells induce autoimmune responses in thyroid tissues
(39). Furthermore, excessive
effector T-cell activation increases the risk of TD by promoting
the release of cytokines such as interleukin-2, interferon and
tumor necrosis factor (40).
Kegasawa et al (41) enrolled 178 patients with HCC treated
with sorafenib. The study identified that a baseline AFP level
>200 ng/ml was an independent risk factor for disease
progression and OS in patients with HCC. These findings align with
the present study: The present study results suggested that a
pretreatment baseline AFP level >200 ng/ml is an independent
risk factor for PFS and OS in patients with HCC. Thus, evaluating
baseline AFP levels contributes to determining clinical prognosis
in patients with HCC. Furthermore, regardless of prior hyperthyroid
phase, the present study revealed that all patients with HCC who
experienced thyroid adverse events ultimately progressed to
hypothyroidism. This result was consistent with previous research
(25,42).
The present study had several limitations. First,
nearly half of the enrolled patients (32/77; 41.6%) lacked baseline
thyroid antibody testing data; therefore, the association between
the post-treatment hypothyroidism incidence and baseline thyroid
antibody levels could not be explored in the present study, which
may be investigated in future research. Second, only a small
proportion of patients developed hyperthyroidism and the small
sample size prevented an analysis of the association between
prognosis and hyperthyroidism. Third, the present study
acknowledges that excluding female patients restricts the
generalizability of the present study findings to women.
Accordingly, future studies may recruit female patients with HCC to
perform sex-specific subgroup analyses and verify the robustness of
the present study findings across sexes. Furthermore, mechanistic
investigation is inherently limited in the present retrospective
study. To mitigate this key limitation, prospective studies may
validate these associations, alongside complementary in
vitro and in vivo experiments aimed at elucidating the
underlying molecular mechanisms in the future. Furthermore, since
the present study was a retrospective single-center study, larger
prospective randomized controlled trials are warranted to confirm
the impact of hypothyroidism on the prognosis in male patients with
HCC treated with PD-1 inhibitors plus TKIs combination therapy.
In conclusion, male patients with HCC who developed
hypothyroidism during PD-1 inhibitors plus TKI therapy exhibited a
more favorable prognosis compared with patients with normal thyroid
function. Furthermore, the present study findings identified
baseline AFP levels as an independent prognostic factor. Future
studies should evaluate baseline serum levels of TSH, TPOAb, TgAb
and AFP in patients with HCC prior to initiation of PD-1 inhibitors
plus TKIs combination therapy. Close monitoring of thyroid function
and antibodies during treatment is key to early prognostic
assessment and timely intervention.
Acknowledgements
Not applicable.
Funding
Funding: No funding was received.
Availability of data and materials
The data generated in the present study may be
requested from the corresponding author.
Authors' contributions
BC wrote the main manuscript text and prepared the
figures and tables. PH and HZ conceived and designed the present
study. BC and MA collected and analyzed the data. PH and HZ confirm
the authenticity of all the raw data. All authors read and approved
the final manuscript.
Ethics approval and consent to
participate
The present study complied with the Declaration of
Helsinki. All of the present study procedures were approved by the
Ethics Committee of Nanjing Second Hospital (approval no.
2024-LS-ky-098; Nanjing, China). Written informed consent was
obtained from all participants included in the present study.
Patient consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing
interests.
Glossary
Abbreviations
Abbreviations:
|
HCC
|
hepatocellular carcinoma
|
|
PD-1
|
programmed cell death protein-1
|
|
TKIs
|
tyrosine kinase inhibitors
|
|
ICI
|
immune checkpoint inhibitor
|
|
OS
|
overall survival
|
|
PFS
|
progression-free survival
|
|
CR
|
complete response
|
|
PD
|
progressive disease
|
|
PR
|
partial response
|
|
SD
|
stable disease
|
|
CI
|
confidence interval
|
|
TSH
|
thyroid-stimulating hormone
|
|
AFP
|
α-fetoprotein
|
|
TgAb
|
thyroglobulin antibody
|
|
TPOAb
|
thyroid peroxidase antibody
|
|
FT3
|
free triiodothyronine
|
|
FT4
|
free thyroxine
|
|
TD
|
thyroid dysfunction
|
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