Co esponding au ho : Du ani Ahsanullah
Copy igh © 2025 Au ho (s) e ain he copy igh o his a icle. This a icle is published unde he e ms o he C ea i e Commons A ibu ion Liscense 4.0.
S udy on he e icacy o adju an TACE plus a ge ed he apy in pa ien s wi h
hepa ocellula ca cinoma a a high isk o ecu ence a e hepa ec omy
Du ani Ahsanullah 1, *, Zainab 2, Shuku ullah 3, Dhi a salsabila 4 and Ul a Du ani 5
1 A ilia ed Hospi al o Nan ong Uni e si y.
2 Gas oen e ology ci il hospi al Ka achi Pakis an.
3 Zhejiang chines medical uni e si y.
4 A ilia ed Hospi al o Nan ong Uni e si y.
5 Is a Medical uni e si y Hyde abad, Pakis an.
Wo ld Jou nal o Biology Pha macy and Heal h Sciences, 2025, 21(01), 140-148
Publica ion his o y: Recei ed on 25 No embe 2024; e ised on 04 Janua y 2025; accep ed on 06 Janua y 2025
A icle DOI: h ps://doi.o g/10.30574/wjbphs.2025.21.1.0007
Abs ac
Objec i e: Pa ien s wi h hepa ocellula ca cinoma (HCC) ha e a high isk o ecu ence a e li e esec ion, and inding
e ec i e adju an he apy is c ucial o imp o ing pa ien p ognosis. The e icacy o ansca he e a e ial
chemoemboliza ion (TACE) combined wi h a ge ed he apy has a ac ed a en ion, bu he e is s ill insu icien
esea ch on i s compa ison wi h TACE alone. The aim o his s udy is o compa e he e icacy di e ences be ween
adju an TACE combined wi h a ge ed he apy and TACE alone in pa ien s wi h high isk o ecu ence o
hepa ocellula ca cinoma a e su ge y, and o e alua e he impac o he wo ea men egimens on pa ien su i al
and ecu ence.
Me hods: This s udy is a e ospec i e coho s udy ha analyzed he p ognosis o adju an TACE combined wi h
a ge ed he apy in high- isk hepa ocellula ca cinoma pa ien s wi h pos ope a i e ecu ence be ween Janua y 2014
and Decembe 2022. The pa ien s we e di ided in o wo g oups, one ecei ing adju an TACE combined wi h a ge ed
he apy, and he o he ecei ing simple TACE ea men . Collec clinical da a, ea men plans, and ollow-up esul s o
pa ien s, and compa e he su i al and ecu ence a es o wo g oups o pa ien s. The main esea ch endpoin s include
o e all su i al (OS) and ecu ence ee su i al (RFS), and compa isons a e made be ween g oups. Apply he COX
p opo ional haza ds eg ession model o conduc uni a ia e and mul i a ia e analyses o OS and RFS, espec i ely.
Resul : A e adjus men o con ounding ac o s, mul i a iable analysis iden i ied ha TACE + a ge ed he apy was
independen ly associa ed wi h be e OS (HR: 0.47; 95% CI: 0.30-0.74; P = 0.001) and RFS (HR: 0.40; 95% CI: 0.20-0.80;
P = 0.010) in pa ien s wi h HCC a a high isk o ecu ence a e hepa ec omy. In addi ion, BCLC s age-C, Child-Pugh
g ade B, p eope a i e ex ahepa ic me as asis, and su gical ma gin > 1cm we e independen isk ac o s o OS o
pa ien s wi h HCC a a high isk o ecu ence a e hepa ec omy. Meanwhile, BCLC s age-C, umo di e en ia ion
(mode a e e sus poo ), and p eope a i e ex ahepa ic me as asis we e independen isk ac o s o RFS o pa ien s
wi h HCC a a high isk o ecu ence a e hepa ec omy.
Conclusion: By analyzing and compa ing he p ognos ic ou comes o adju an TACE combined wi h o wi hou a ge ed
he apy in high- isk hepa ocellula ca cinoma pa ien s wi h pos ope a i e ecu ence, his s udy ound ha adju an
TACE combined wi h a ge ed he apy had a be e p ognosis han TACE alone: median OS and median RFS we e longe .
The combina ion o adju an TACE and a ge ed he apy is an independen in luencing ac o o be e OS and RFS,
espec i ely.
Wo ld Jou nal o Biology Pha macy and Heal h Sciences, 2025, 21(01), 140-148
141
Keywo ds: Hepa ocellula Ca cinoma (HCC); Recu ence; T ans-a e ial Chemoemboliza ion; Ta ge ed The apy;
Li e Resec ion
1. In oduc ion
Hepa ocellula Ca cinoma (HCC) s ands as a o midable global heal h challenge, ep esen ing he mos p e alen
p ima y li e malignancy and anking as he ou h leading cause o cance - ela ed mo ali y wo ldwide [1].
Cha ac e ized by i s associa ion wi h ch onic li e diseases, such as ci hosis, HCC poses a complex clinical scena io
equi ing a mul i- ace ed unde s anding o e ec i e managemen . Hepa ec omy, o su gical emo al o he umo -
bea ing po ion o he li e , s ands as a p ima y cu a i e op ion o HCC. Howe e , he pos ope a i e landscape is
ma ked by he pe sis en h ea o ecu ence, necessi a ing a comp ehensi e examina ion o i s incidence, con ibu ing
ac o s, and he associa ed challenges in managemen [2-3]. O all li e p ima y umo s, hepa ocellula ca cinoma (HCC)
accoun s o abou 90% o cases. Abou 85% o pa ien s wi h ci hosis a e also diagnosed wi h hepa ocellula
ca cinoma. Cu en ly, HCC anks as he i h mos equen cause o cance globally. HCC is he second mos common
cause o cance - ela ed mo ali y in men, a e lung cance [2-4]. HCC has an 18% i e-yea su i al a e, second only o
panc ea ic cance . Hepa i is caused by i uses (hepa i is B and hepa i is C), alcoholic li e disease, and non-alcoholic
a y li e disease/s ea ohepa i is a e impo an isk ac o s o hepa ocellula cance . In 80%–90% o ci hosis
pa ien s, HCC de elops. In pa ien s wi h ci hosis, he annual incidence o HCC is 2-4% [5].
La ge ma gins ha e been ecommended o non-ana omic esec ions o small (<5 cm) HCCs, as well as HCCs wi h
mic o ascula in asion, ci hosis- ee, o high le els o alpha- e op o ein (AFP) [6]. O he s udies, howe e , showed ha
pos ope a i e ecu ence a es and pa e ns we e una ec ed by umo -nega i e ma gins o ≤1 mm and ma gins <1 cm
[7]. High- isk ecu ence no only poses challenges o he clinical managemen o HCC bu also signi ican ly impac s
pa ien p ognosis and quali y o li e. The delica e balance be ween agg essi e in e en ion and p ese ing pa ien s'
o e all well-being unde sco es he complexi y o managing ecu en HCC [8].
A comp ehensi e unde s anding o HCC, including i s p opensi y o ecu ence a e Hepa ec omy, is essen ial o
ad ancing he apeu ic s a egies. The subsequen sec ions will del e in o he speci ic challenges posed by high- isk
ecu ence and explo e he limi a ions o cu en he apies, highligh ing he c i ical need o inno a i e app oaches o
enhance he o e all managemen o HCC [9].
T an’s ca he e a e ial chemoemboliza ion (TACE) is a widely u ilized pos ope a i e adju an he apy o
hepa ocellula ca cinoma (HCC). TACE combines he adminis a ion o chemo he apeu ic agen s di ec ly in o he
umo - eeding a e ies wi h subsequen emboliza ion. This dual app oach aims o achie e localized chemo he apy
deli e y while inducing ischemia in he umo , e ec i ely a ge ing esidual cance cells [10]. Ad ancemen s in
unde s anding he molecula pa hways in ol ed in HCC ha e led o he de elopmen o a ge ed he apies. So a enib
and len a inib, bo h mul i-kinase inhibi o s, ha e demons a ed e icacy in pos ope a i e se ings by inhibi ing
angiogenesis and umo cell p oli e a ion [11]. Immuno he apeu ic agen s, such as ni olumab and pemb olizumab, ha e
demons a ed po en ial in he pos ope a i e se ing by ha nessing he immune sys em o a ge esidual cance cells.
Ea ly clinical ials ha e shown encou aging esul s, sugges ing a ole o immuno he apy in p e en ing HCC ecu ence
[12].
Loco- egional he apies, including adio equency abla ion (RFA) and mic owa e abla ion (MWA), play a c ucial ole in
managing pos ope a i e HCC ecu ence. These echniques o e a ge ed des uc ion o small esidual umo s,
imp o ing ou comes in selec pa ien popula ions [13].
2. Ma e ial and me hods
2.1. S udy Design and Pa icipan s
This s udy was a e ospec i e coho analysis designed o e alua e he e icacy o adju an TACE plus a ge ed he apy
e sus TACE alone in pa ien s wi h HCC a a high isk o ecu ence a e Hepa ec omy. Pa ien s who unde wen
Hepa ec omy o HCC be ween Janua y 2014 and Decembe 2022 om Nan ong Uni e si y A ilia ed Hospi al we e
e ospec i ely analyzed. The diagnosis o HCC was con i med by pos ope a i e his opa hological examina ion o he
esec ed specimens. Ta ge ed he apy used in his s udy included Len a inib (12 mg/d o bodyweigh ≥ 60 kg o 8
mg/d o bodyweigh < 60 kg o ally once daily), (400 mg wice a day) o lapa inib (250-500 mg o ally once daily).
Wo ld Jou nal o Biology Pha macy and Heal h Sciences, 2025, 21(01), 140-148
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2.2. Inclusi e C i e ia
The inclusion c i e ia we e as ollows: (a) pa ien s diagnosed wi h HCC a a high isk o ecu ence a e Hepa ec omy;
(b) unde gone Hepa ec omy as he p ima y ea men o HCC; (c) ea ed wi h adju an TACE plus a ge ed he apy o
TACE alone; (d) Child-Pugh A o B li e unc ion; (e) Eas e n Coope a i e Oncology G oup (ECOG) pe o mance s a us
o 0 o 1; and ( ) a ailable imaging and clinical ollow-up da a.
2.3. Exclusi e C i e ia
The exclusion c i e ia we e as ollows: (a) a his o y o o he malignancies wi hin he pas 5 yea s; (b) incomple e
medical eco ds o insu icien ollow-up da a; (c) unde gone loco egional he apy o he han TACE o hei HCC; (d)
Child-Pugh class C li e ci hosis; (e) se e e unde lying ca diac, pulmona y, o enal disease.
2.4. S a is ical Analysis
S a is ical analysis was pe o med using he IBM SPSS e sion 26.0. Con inuous a iables we e exp essed as mean ±
s anda d de ia ions o medians ( ange) and in e qua ile anges as app op ia e. Ca ego ical a iables we e epo ed as
numbe s and p opo ions. Con inuous a iables we e compa ed using he s uden ’s es and ca ego ical a iables we e
compa ed using he Fishe ’s exac es o he χ2 es wi h
Ya e’s con inui y co ec ion, as app op ia e. Su i al cu es we e gene a ed using he Kaplan-Meie me hod and
compa ed using he log- ank es . All a iables wi h a P alue < 0.1 in he Uni a iable analyses we e included in he
mul i a iable Cox- eg ession analyses. Haza d a ios (HRs) o OS and RFS we e calcula ed wi h 95% con idence
in e als (CIs). All s a is ical es s we e wo- ailed, and a P alue <
0.05 was conside ed s a is ically signi ican .
3. Resul s
3.1. Compa isons o Baseline Cha ac e is ics
A o al o 171 high- isk ecu en HCC pa ien s a e li e esec ion we e included in he s udy, including 102 cases in
he TACE g oup and 69 cases in he TACE + a ge ed he apy g oup. Compa ison o baseline pa ien cha ac e is ics and
ope a i e a iables among he g oups a e no ed in Table 1. The e is no signi ican di e ence in mos a iables be ween
he wo g oups.
Table 1 Baseline Cha ac e is ics
TACE g oup
（n = 102）
TACE + a ge ed he apy（n = 69）
P
Sex (male)
82 (80.4%)
57 (82.6%)
0.715
Age (yea s)
59±9
58±10
0.415
ECOG PS (1)
44 (43.1%)
37 (53.6%)
0.178
BCLC s age
0.269
0
9 (8.8%)
13 (18.8%)
A
79 (77.5%)
46 (66.7%)
B
6 (5.9%)
5 (7.2%)
C
8 (7.8%)
5 (7.2%)
Ci hosis
63 (61.8%)
54 (78.3%)
0.023
Child–Pugh g ade (B)
6 (5.9%)
2 (2.9%)
0.351
P eope a i e ex ahepa ic me as asis
2 (2.0%)
0 (0.0%)
0.149
Mic o ascula in asion
28 (27.5%)
14 (20.3%)
0.286
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P eope a i e AFP (> 400μg/l)
81 (79.4%)
56 (81.2%)
0.779
La ges umo size (> 5 cm)
43 (42.2%)
23 (33.3%)
0.245
Tumo numbe (mul iple)
16 (15.7%)
10 (14,5%)
0.831
Sa elli e nodules (yes e sus no)
10 (9.8%)
9 (13.0%)
0.508
Tumo di e en ia ion
0.572
poo
46 (45.1%)
26 (37.7%)
mode a e
45 (44.1%)
36 (52.2%)
3.2. Compa isons o Long- e m Ou comes
Compa ison o long- e m ou comes among he h ee g oups a e no ed in Table 2. The TACE + a ge ed he apy g oup
had be e OS (median: 79.7 s. 45.9 mon hs, P = 0.002) and RFS (median: 36.5 s. 15.0 mon hs, P ＜ 0.001) e sus he
TACE g oup. The OS and RFS cu es among he g oups a e shown in Figu e 1 and Figu e 2, espec i ely.
Figu e 1 Kaplan- Meie Analysis o o e all su i al
Wo ld Jou nal o Biology Pha macy and Heal h Sciences, 2025, 21(01), 140-148
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Figu e 2 Kaplan- Meie Analysis o Recu ence ee su i al
3.3. Uni a iable and mul i a iable analysis o OS and RFS
Uni a iable and mul i a iable Cox- eg ession analyses we e used o iden i y independen isk ac o s o OS and RFS
(Tables 2 and Table 3). A e adjus men o con ounding ac o s, mul i a iable analysis iden i ied ha TACE + a ge ed
he apy was independen ly associa ed wi h be e OS (HR: 0.47; 95% CI: 0.30-0.74; P = 0.001) and RFS (HR: 0.40; 95%
CI: 0.20-0.80; P = 0.010) in pa ien s wi h HCC a a high isk o ecu ence a e Hepa ec omy.
In addi ion, BCLC s age-C, Child-Pugh g ade B, p eope a i e ex ahepa ic me as asis, and su gical ma gin > 1cm we e
independen isk ac o s o OS o pa ien s wi h HCC a a high isk o ecu ence a e Hepa ec omy. Meanwhile, BCLC
s age-C, umo di e en ia ion (mode a e e sus poo ), and p eope a i e ex ahepa ic me as asis we e independen isk
ac o s o RFS o pa ien s wi h HCC a a high isk o ecu ence a e Hepa ec omy.
Table 2 Uni a iable and Mul i a iable Analysis o OS
Uni a iable Analysis
Mul i a iable Analysis
HR (95% CI)
P
HR (95% CI)
P
TACE + a ge ed he apy e sus TACE
0.48 (0.32-0.72)
<0.001
0.47 (0.30-0.74)
0.001
Sex (male e sus emale)
1.80 (0.76-4.25)
0.181
Age (yea s)
1.01 (0.98-1.04)
0.584
ECOG PS (1 e sus 0 )
1.03 (0.57-1.84)
0.934
BCLC s age
0
1.00
1.00
A
1.23 (0.48-3.21)
0.666
0.92 (0.32-2.65)
0.875
B
3.70 (0.98-13.9)
0.053
2.39 (0.49-11.70)
0.283
C
6.02 (2.04-17.76)
0.001
4.03 (1.13-14.41)
0.032
Ci hosis (yes e sus no)
0.72 (0.38-1.35)
0.306
Child–Pugh g ade (B e sus A)
4.39 (1.70-11.34)
0.002
3.67 (1.26-10.67)
0.017
P eope a i e ex ahepa ic me as asis
(yes e sus no)
27.56 (5.91-128.4)
<0.001
15.14 (2.52-90.98)
0.003
Mic o ascula in asion (yes e sus no)
2.11 (1.11-4.01)
0.023
0.96 (0.45-2.07)
0.920
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P eope a i e AFP (> 400 e sus
≤ 400μg/l)
1.99 (1.06-3.74)
0.031
1.26 (0.58-2.74)
0.558
La ges umo size (> 5 e sus ≤ 5 cm)
1.94 (1.08-3.47)
0.026
1.77 (0.89-3.53)
0.106
Renewal 2
Uni a iable Analysis
Mul i a iable Analysis
HR (95% CI)
P
HR (95% CI)
P
Tumo numbe (mul iple e sus soli a y)
1.68 (0.78-3.63)
0.186
Sa elli e nodules (yes e sus no)
1.93 (1.12-3.33)
0.018
0.91 (0.35-2.39)
0.851
Tumo di e en ia ion poo
1.00
mode a e
0.40 (0.21-0.75)
0.004
0.50 (0.24-1.01)
0.052
well
0.43 (0.16-1.17)
0.098
0.98 (0.31-3.12)
0.971
Su gical app oach (lapa oscopic e sus open )
1.05 (0.41-2.69)
0.916
Su gical ma gin (> 1 e sus ≤ 1 cm)
0.58 (0.31-1.09)
0.092
0.41 (0.19-0.88)
0.022
Table 3 Uni a iable and Mul i a iable Analysis o RFS
Uni a iable Analysis
Mul i a iable Analysis
HR (95% CI)
P
HR (95% CI)
P
TACE + a ge ed he apy e sus TACE
0.39 (0.21-0.73)
0.004
0.40 (0.20-0.80)
0.010
Sex (male e sus emale)
0.61 (0.36-1.04)
0.071
0.70 (0.40-1.22)
0.209
Age (yea s)
1.00 (0.97-1.03)
0.636
ECOG PS (1 e sus 0 )
0.96 (0.64-1.42)
0.957
BCLC s age 0
1.00
1.00
A
1.58 (0.83-2.98)
0.162
1.42 (0.72-2.81)
0.309
B
2.72 (1.05-7.06)
0.040
2.03 (0.77-5.40)
0.154
C
3.41 (1.49-7.78)
0.004
2.58 (1.06-6.33)
0.038
Ci hosis (yes e sus no)
0.80 (0.52-1.22)
0.292
Child–Pugh g ade (B e sus A)
1.34 (0.54-3.31)
0.527
P eope a i e ex ahepa ic me as asis
(yes e sus no)
12.33 (2.86-53.2)
0.001
5.51 (1.22-24.83)
0.026
Mic o ascula in asion (yes e sus no)
1.72 (1.12-2.64)
0.013
1.18 (0.73-1.91)
0.506
P eope a i e AFP (> 400 e sus
≤ 400μg/l)
1.60 (1.01-2.55)
0.045
1.28 (0.78-2.13)
0.330
La ges umo size (> 5 e sus ≤ 5 cm)
1.43 (0.96-2.13)
0.076
1.15 (0.74-1.81)
0.530
Tumo numbe (mul iple e sus soli a y)
1.14 (0.65-2.02)
0.645
Sa elli e nodules (yes e sus no)
1.48 (0.86-2.58)
0.161
Tumo di e en ia ion poo
1.00
1.00
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Renewal 3
Uni a iable Analysis
Mul i a iable Analysis
HR (95% CI)
P
HR (95% CI)
P
mode a e
0.38 (0.25-
0.58)
<0.001
0.44 (0.28-
0.70)
<0.001
well
0.49 (0.25-
0.99)
0.045
0.66 (0.31-
1.42)
0.286
Su gical app oach (lapa oscopic
e sus open )
1.30 (0.74-
2.31)
0.363
Su gical ma gin (> 1 e sus ≤ 1 cm)
0.872 (0.57-
1.33)
0.524
4. Discussion
The e is a clea ela ionship be ween he se e i y o he disease and he p ognosis, as seen by he dec easing RFS and
OS as BCLC s aging becomes in e media e om low. This is in line wi h he clinical suspicion ha hepa ocellula
ca cinoma in i s ad anced s ages may ha e wo se p ognoses. Imp o ed clinical ou comes ha e esul ed om he s udy's
expe imen al se ings, which may poin he way o be e pos ope a i e ca e and longe pa ien su i al a es [14].
Pa ien s wi h HCC and main ained li e unc ion ypically unde go cu a i e Hepa ec omy. The e is a high a e o
ecu ence ollowing Hepa ec omy, which makes he long- e m su i al a e unsa is ac o y. Among he many
un a o able ac o s linked o ecu ence and e y poo RFS and OS a e cu a i e esec ion, MVI s ands ou [15-16].
P elimina y esea ch ound ha MVI aised ecu ence p obabili ies [17-18] and lowe ed su i al odds (4.70%, 95% CI:
1.24-17.80). A me a-analysis and ho ough assessmen o andomized ials e ealed ha adju an TACE he apy did
no seem o be help ul o pa ien s wi h low- isk ecu en HCC. Adju an he apy based on s anda dized an i i al and
hepa op o ec i e ea men s is ad ised o pa ien s a high isk o HCC ecu ence (i.e., umo diame e > 5 cm,
combined ascula in asion, mul iple umo s o sa elli e lesions, and esidual lesions). This may imp o e disease- ee
su i al (DFS), RFS, and OS.[19-20]. Due o he ac ha MVI mos ly dissemina e by po al enous b anches and can mo e
in bo h di ec ions when po al enous blood lows, his ana omical s a e is hough o be equi ed o umo
dissemina ion in ci cula ion[21]. The p esence o MVI is co ela ed wi h a numbe o ac o s, such as he size, shape, and
deg ee o di e en ia ion o hepa ic neoplasms [22]. he in asion o a essel ha is a leas 1 cm away om he umo
capsule[23]. The e ec o choosing he igh ma gin o ana omic esec ion on he pos ope a i e cou se o pa ien s wi h
HCC has been he subjec o nume ous s udies; ne e heless, he signi icance o his disco e y has been called in o
ques ion. A 2 cm ma gin sa ely lowe s he pos ope a i e ecu ence a e and imp o es su i al ou comes when
compa ed o esec ion ma gins be ween 1 and 2 cm, acco ding o esea ch [24]. A ew s udies sugges ha in o de o
e adica e mic oscopic lesions and educe he chance o ecu ence, he majo i y o pa ien s should ha e a esec ion
ma gin o a leas 1.0 cm.[25]. In o de o emo e mic oscopic lesions, a b oade esec ion ma gin is p e e ed, acco ding
o a small numbe o s udies [26]. Howe e , he majo i y o pa ien s in hese coho s had ci hosis. P ese ing non-
umo ous li e pa enchyma in ci ho ic pa ien s is essen ial o p e en pos ope a i e li e ailu e.
As o igh now, no adju an ea men o HCC has been app o ed o p e en ecu ence. Many adju an s he apy ha e
been in es iga ed o HCC a e cu a i e esec ion wi h he goal o educing ecu ence and ex ending OS. These
ea men s consis o TACE, immunological he apies, molecula ly a ge ed medicines, and adia ion he apy (RT).
Howe e , hese he apies don' always yield he expec ed ou comes.[27-28].
5. Conclusion
By analyzing and compa ing he p ognos ic ou comes o adju an TACE combined wi h o wi hou a ge ed he apy in
high- isk hepa ocellula ca cinoma pa ien s wi h pos ope a i e ecu ence, his s udy ound ha adju an TACE
combined wi h a ge ed he apy had a be e p ognosis han TACE alone: median OS and median RFS we e longe . The
combina ion o adju an TACE and a ge ed he apy is an independen in luencing ac o o be e OS and RFS,
espec i ely.
Wo ld Jou nal o Biology Pha macy and Heal h Sciences, 2025, 21(01), 140-148
147
Compliance wi h e hical s anda ds
Disclosu e o con lic o in e es
No con lic o in e es o be disclosed.
S a emen o in o med consen
In o med consen was ob ained om all indi idual pa icipan s included in he s udy.
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