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Bane jee e al. In e na ional Jou nal o Cu en Pha maceu ical Re iew and Resea ch
665
O iginal Resea ch A icle
A S udy o Assess he P ese a ion o Hea ing Func ion in Cochlea
Spa ing Radia ion The apy in Pa ien s o Head and Neck Ca cinoma
T ea ed wi h De ini i e Concomi an Chemo-Radia ion
Diya Bane jee1, Shampa Mai y2, Apu ba Bikash P amanik3, Sub a a Cha e jee4,
P asan a Kuma Gu e5, Sap a shi Bane jee6
1Senio Residen , MD (Radia ion Oncology), Depa men o Radia ion Oncology, Acha ya Ha iha Pos
G adua e Ins i u e o Cance , Cu ack, Odisha 753007
2Assis an P o esso , MD (Radia ion Oncology), Depa men o Radia ion Oncology, Mu shidabad
Medical College and Hospi al, Be hampo e, Wes Bengal 742101
3Associa e P o esso , MD (Gene al Medicine), DM (Ca diology), Depa men o Gene al Medicine, Deben
Maha a Go e nmen Medical College & Hospi al, Pu ulia, Wes Bengal 700064
4P o esso , MD (Radia ion Oncology), Depa men o Radia ion Oncology, Medical College & Hospi al,
Kolka a, Wes Bengal 700073
5Associa e P o esso , MS (ENT), Depa men o ENT, Medical College & Hospi al, Kolka a, Wes Bengal
700073
6Assis an P o esso , MD (Radia ion Oncology), Depa men o Radia ion Oncology, Medical College &
Hospi al, Kolka a, Wes Bengal 700073
Recei ed: 01-07-2025 / Re ised: 16-08-2025 / Accep ed: 26-08-2025
Co esponding Au ho : D . Apu ba Bikash P amanik
Con lic o in e es : Nil
Abs ac
In oduc ion: Head and neck ca cinoma (HNC) is commonly ea ed wi h de ini i e concomi an chemo-
adia ion (CCRT), which, while e ec i e, can esul in signi ican ea men - ela ed oxici ies, including
senso ineu al hea ing loss due o adia ion exposu e o he cochlea.
Aims: Cochlea -spa ing adia ion he apy (CSRT) aims o educe adia ion dose o he cochlea while
main aining umo con ol, po en ially p ese ing hea ing unc ion.
Me hods: This s udy is a single-ins i u ional p ospec i e obse a ional s udy conduc ed a he Depa men o
Radio he apy, Medical College and Hospi al, Kolka a, om Oc obe 2022 o Feb ua y 2024. The s udy
popula ion included pa ien s a ending he adio he apy ou pa ien depa men wi h biopsy-p o en locally
ad anced ca cinoma o he head and neck, who had good pe o mance s a us and sa is ac o y ca diological
s a us, and we e planned o ecei e concu en chemo adio he apy as de ini i e ea men .
Resul s: Bone-masked pu e one audiome y showed ha cochlea -spa ing chemo adia ion he apy led o
equency- and ime-dependen inc eases in hea ing h esholds. A 250 Hz, h esholds inc eased sligh ly
immedia ely pos - ea men and ose p og essi ely a 3 and 6 mon hs, eaching highly signi ican le els (up o
5.86 dB, p < 0.001). A 500 Hz, immedia e changes we e minimal, bu signi ican h eshold shi s we e
obse ed a 3 and 6 mon hs (up o 4.11 dB, p < 0.001). A 1000 Hz, immedia e pos - ea men changes we e
negligible, while signi ican inc eases occu ed a 3 and 6 mon hs (up o 3.61 dB, p < 0.001). Linea eg ession
e ealed a dose-dependen ela ionship be ween cochlea maximum adia ion doses (Dmax) and hea ing
h esholds o e ime, wi h s onge co ela ions a 3 and 6 mon hs ac oss all equencies, indica ing ha highe
cochlea doses a e associa ed wi h g ea e long- e m hea ing loss.
Conclusion: Cochlea -spa ing adia ion he apy du ing de ini i e CCRT o head and neck ca cinoma is
easible and e ec i ely p ese es hea ing unc ion, pa icula ly in low- o mid- equency anges, wi hou
comp omising oncologic ou comes. Implemen a ion o cochlea dose cons ain s in adio he apy planning
should be conside ed o minimize o o oxici y in HNC pa ien s.
Keywo ds: Head and neck ca cinoma, cochlea -spa ing adio he apy, hea ing p ese a ion, chemo- adia ion,
senso ineu al hea ing loss, in ensi y-modula ed adia ion he apy (IMRT).
This is an Open Access a icle ha uses a unding model which does no cha ge eade s o hei ins i u ions o access and dis ibu ed unde
he e ms o he C ea i e Commons A ibu ion License (h p://c ea i ecommons.o g/licenses/by/4.0) and he Budapes Open Access
Ini ia i e (h p://www.budapes openaccessini ia i e.o g/ ead), which pe mi un es ic ed use, dis ibu ion, and ep oduc ion in any medium,
p o ided o iginal wo k is p ope ly c edi ed.
In oduc ion
Head and neck ca cinomas (HNCs), encompassing
malignancies o he o al ca i y, pha ynx, la ynx,
and nasopha ynx, ep esen a signi ican clinical
challenge. The s anda d ea men o locally
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Bane jee e al. In e na ional Jou nal o Cu en Pha maceu ical Re iew and Resea ch
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ad anced HNC o en in ol es de ini i e concu en
chemo adio he apy (CCRT), combining adia ion
he apy (RT) wi h chemo he apy, ypically using
cispla in as a adiosensi ize [1]. While his
app oach has ma kedly imp o ed su i al a es, i
is associa ed wi h a spec um o acu e and long-
e m oxici ies, no ably senso ineu al hea ing loss
(SNHL). The cochlea, being a adiosensi i e o gan,
is pa icula ly ulne able o adia ion-induced
damage, leading o i e e sible hea ing impai men
in many pa ien s [2].
The cochlea's ana omical loca ion wi hin he
empo al bone and i s in ica e s uc u e make i
challenging o spa e du ing adia ion ea men [3].
T adi ional adio he apy echniques o en esul in
signi ican exposu e o he cochlea o he apeu ic
doses. Howe e , ad ancemen s in adia ion
deli e y, pa icula ly in ensi y-modula ed adia ion
he apy (IMRT), ha e enabled mo e p ecise
a ge ing o umo olumes while minimizing he
dose o su ounding heal hy issues, including he
cochlea [4]. S udies ha e demons a ed ha IMRT
can e ec i ely educe he cochlea dose, he eby
p ese ing hea ing unc ion wi hou comp omising
oncologic ou comes [5].
Despi e hese ad ancemen s, he isk o SNHL
emains a conce n, especially when combined wi h
he o o oxic e ec s o cispla in. Resea ch indica es
ha cispla in-induced hea ing loss (CIHL) is dose-
dependen and may be exace ba ed by concu en
RT [6]. No ably, a s udy compa ing RT and CCRT
pa ien s ound a signi ican ly highe incidence o
SNHL in he CCRT g oup, wi h cochlea doses
exceeding 50 Gy co ela ing wi h inc eased hea ing
loss [7]. The cumula i e o o oxic e ec s o RT and
chemo he apy necessi a e a ee alua ion o
ea men planning s a egies. Implemen ing
cochlea -spa ing echniques in RT planning is
impe a i e o mi iga e he isk o SNHL. Eme ging
da a sugges ha op imizing adia ion plans o
minimize cochlea dose is easible and can be
achie ed wi hou comp omising umo con ol [8].
Fo ins ance, s udies ha e shown ha cochlea-
spa ing op imized adio he apy o nasopha yngeal
ca cinoma can signi ican ly educe cochlea dose
beyond cu en QUANTEC cons ain s, leading o
imp o ed hea ing p ese a ion [9]. Fu he mo e,
ad ancemen s in imaging and ea men planning
echnologies, such as syn he ic MRI-aided au o-
delinea ion o cone-beam CT-guided adap i e
adio he apy, ha e enhanced he p ecision o
cochlea spa ing. These echnologies acili a e
accu a e delinea ion o he cochlea and o he
o gans-a - isk, enabling mo e e ec i e spa ing and
po en ially educing he incidence o SNHL [10]. In
ligh o hese conside a ions, his s udy aims o
assess he p ese a ion o hea ing unc ion in
pa ien s wi h HNC unde going de ini i e CCRT
u ilizing cochlea -spa ing adia ion he apy
echniques. By e alua ing audiological ou comes
and co ela ing hem wi h dosime ic da a, he
s udy seeks o es ablish e idence-based guidelines
o cochlea dose cons ain s and in o m clinical
p ac ice o enhance he quali y o li e o HNC
pa ien s pos - ea men .
Ma e ials and Me hods
S udy Design: A single ins i u ional p ospec i e
obse a ional s udy.
Place o s udy: Depa men o Radio he apy,
Medical College and Hospi al, Kolka a.
Pe iod o s udy: The pe iod o he s udy will be
om Oc obe 2022 o Feb ua y 2024.
S udy Popula ion: Pa ien s a ending he
adio he apy OPD o Medical College and Hospi al
wi h biopsy p o en Locally Ad anced ca cinoma
o Head and Neck wi h good pe o mance s a us
and good ca diological s a us who will ecei e
Concu en Chemo adio he apy as de ini i e
ea men .
S udy Va iables
• Dependan a iable
• p e- ea men
• Pai ed T es s
Inclusion C i e ia
• Pa ien s wi h his ologically p o en ca cinoma
o nasopha ynx, o opha ynx, la yngopha ynx,
la ynx, o al ca i y, sali a y glands, pa anasal
sinuses, in hei locally ad anced s age (III-
IVA) who will be ea ed by con o mal
Radio he apy along wi h concu en cispla in.
• Male and emale pa ien s be ween he age o
18 o 65 yea s.
• Adequa e pe o mance s a us (Ka no sky
pe o mance sco e 70 o mo e).
• Haema ological, enal, hepa ic unc ion wi hin
no mal limi .
• Baseline audiog am and speech disc imina ion
sco e demons a ing good cochlea ese e.
• P o ision o in o med consen .
• Pa ien s willing o a end OPD o long e m
ollow up
Exclusion C i e ia
• P io chemo he apy o adio he apy o he
p esen disease.
• E idence o uncon olled co-mo bid
condi ion(s) (Uncompensa ed espi a o y,
ca diac, hepa ic and enal disease).
• Poo cochlea ese e.
• Pa ien s unwilling o ollow-up.
S a is ical Analysis: All collec ed and p ope ly
abula ed da a a e o be analyzed using s anda d
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s a is ical so wa e SPSS. Desc ip i e s a is ical
pa ame e s will be eco ded and analyzed.
Resul
Table 1: Pai ed T es s o hea ing h esholds as measu ed by bone masked pu e one audiome ies be o e
and a e ea men s a speci ic in e als a e: Fo le ea :
Pai ed Di e ences
Sig. (2-
Tailed)
Mean
S d.
De ia i
on
S d.
E o
Mean
Lowe
Uppe
d
p e- ea men 250Hz and
immedia e pos ea men
-0.417
1.22766
0.20461
-0.832
-0.00129
-2.036
3
5
0.049
p e- ea men 250Hz and pos
-1.417
2.40684
0.40114
-2.231
-0.60231
-3.532
3
5
0.001
p e- ea men 250Hz and pos
-5.861
4.1207
0.68678
-7.255
-4.46687
-8.534
3
5
0
p e- ea men 500Hz and
immedia e pos
-0.417
1.40153
0.23359
-0.891
0.05754
-1.784
3
5
0.083
p e- ea men 500Hz and pos
3 mon hs 500Hz
-1.417
2.40684
0.40114
-2.231
-0.60231
-3.532
3
5
0.001
p e- ea men 500Hz and pos
6 mon hs 500Hz
-4.111
3.89709
0.64951
-5.43
-2.79253
-6.33
3
5
0
p e- ea men 1000Hz and
immedia e pos
-0.056
0.41019
0.06836
-0.194
0.08323
-0.813
3
5
0.422
p e- ea men 1000Hz and
pos 3 mon hs
-3.611
2.58874
0.43146
-4.487
-2.73521
-8.37
3
5
0
Table 2: S a is ically signi ican hea ing loss has been no iced o all measu ed equencies ( iz 250Hz,
500Hz, 1000Hz, 2000Hz, 4000Hz and 8000Hz) a 3 d and 6 h mon hs pos - ea men
Pai ed Di e ences
Sig. (2-
Tailed)
Mean
S d.
De ia io
n
S d.
E o
Mean
In e al o he
Di e ence
d
Lowe
Uppe
p e- ea men 250Hz and
immedia e pos ea men
250Hz
-0.556
1.59364
0.26561
-1.095
-0.01635
-2.092
35
0.044
p e- ea men 250Hz and
pos 3 mon hs 250Hz
-2.5
3.04725
0.50787
-3.531
-1.46896
-4.922
35
0
p e- ea men 250Hz and
pos 6 mon hs 250Hz
-5.861
4.04371
0.67395
-7.229
-4.49292
-8.697
35
0
p e- ea men 500Hz and
immedia e pos ea men
500Hz
0
1.85164
0.30861
-0.627
0.6265
0
35
1
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Table 3: Linea eg ession o show co ela ion be ween Dmax (conside ed as independen a iable in
each case) and PTA sco e ( he dependan a iable) o di e en equencies o he le ea a e abula ed
as unde
Dependan a iable
R2
Adjus ed
R
P alue
Equa ion
Squa e
Immedia e Pos ea men
250Hz
0.003
-0.026
0.745
pos 3mo250Hz
0.213
0.19
0.005
Conside ing y=(m)x+c: PTA sco e =
(0.001) × dmax+ 13.373
pos 6mo250Hz
0.506
0.491
0
Conside ing y=(m)x+c: PTA sco e =
(0.003) × dmax+15.950
Immedia e Pos ea men
250Hz
0.041
0.013
0.237
pos 3mo500Hz
0.213
0.19
0.005
Conside ing y=(m)x+c: PTA sco e =
(0.001) × dmax+ 13.373
pos 6mo500Hz
0.531
0.517
0
Conside ing y=(m)x+c: PTA sco e =
(0.003) × dmax+14.059
immedia e pos ea men
1000Hz
0.014
-0.015
0.49
pos 3mo1000Hz
0.266
0.244
0.001
Conside ing y=(m)x+c: PTA sco e =
(0.002) × dmax+18.983
pos 6m1000Hz
0.57
0.558
0
Conside ing y=(m)x+c: PTA
Hea ing h esholds measu ed by bone-masked pu e
one audiome y showed a s a is ically signi ican
inc ease a lowe equencies ollowing cochlea -
spa ing chemo adia ion he apy. A 250 Hz, he
immedia e pos - ea men mean h eshold inc eased
sligh ly by 0.42 dB, which was bo de line
signi ican ( = –2.036, p = 0.049). A 3 mon hs
pos - ea men , he mean h eshold inc eased by
1.42 dB ( = –3.532, p = 0.001), and a 6 mon hs, a
mo e p onounced inc ease o 5.86 dB was
obse ed, which was highly signi ican ( = –8.534,
p < 0.001). Simila ly, a 500 Hz, immedia e pos -
ea men changes we e no s a is ically signi ican
(–0.42 dB, = –1.784, p = 0.083), whe eas
h esholds a 3 mon hs and 6 mon hs inc eased by
1.42 dB ( = –3.532, p = 0.001) and 4.11 dB ( = –
6.33, p < 0.001), espec i ely. A 1000 Hz,
immedia e pos - ea men changes we e minimal
and no signi ican (–0.056 dB, = –0.813, p =
0.422), bu a 3 mon hs pos - ea men , he mean
h eshold inc eased by 3.61 dB, showing a highly
signi ican change ( = –8.37, p < 0.001).
Bone-masked pu e one audiome y demons a ed
equency- and ime-dependen changes in hea ing
h esholds ollowing cochlea -spa ing
chemo adia ion he apy. A 250 Hz, he immedia e
pos - ea men mean h eshold inc eased by 0.56
dB, which was s a is ically signi ican ( = –2.092,
p = 0.044). A 3 mon hs pos - ea men , he mean
h eshold inc eased by 2.50 dB ( = –4.922, p <
0.001), and a 6 mon hs, a mo e p onounced
inc ease o 5.86 dB was obse ed ( = –8.697, p <
0.001). A 500 Hz, immedia e pos - ea men
changes we e negligible, wi h a mean di e ence o
0 dB, showing no s a is ical signi icance ( = 0, p =
1).
Bone-masked pu e one audiome y demons a ed
equency- and ime-dependen changes in hea ing
h esholds ollowing cochlea -spa ing
chemo adia ion he apy. A 250 Hz, immedia e
pos - ea men h esholds inc eased sligh ly by 0.56
dB, which was s a is ically signi ican ( = –2.092,
p = 0.044), and mo e p onounced inc eases we e
obse ed a 3 mon hs (2.50 dB, = –4.922, p <
0.001) and 6 mon hs (5.86 dB, = –8.697, p <
0.001). A 500 Hz, immedia e pos - ea men
changes we e negligible (0 dB, = 0, p = 1), while
inc eases a 3 mon hs (1.42 dB, = –3.532, p =
0.001) and 6 mon hs (4.11 dB, = –6.33, p < 0.001)
we e signi ican . A 1000 Hz, immedia e pos -
ea men changes we e minimal (–0.056 dB, = –
0.813, p = 0.422), bu signi ican inc eases we e
no ed a 3 mon hs (3.61 dB, = –8.37, p < 0.001).
Linea eg ession analysis showed ha hea ing
h esholds p og essi ely co ela ed wi h cochlea
maximum adia ion dose (Dmax) o e ime.
Immedia e pos - ea men h esholds a all
equencies we e no signi ican ly associa ed wi h
Dmax; howe e , a 3 and 6 mon hs, signi ican
dose-dependen ela ionships eme ged. Fo 250 Hz,
PTA sco es inc eased as PTA = 0.001 × Dmax +
13.373 a 3 mon hs and PTA = 0.003 × Dmax +
15.950 a 6 mon hs (R² = 0.213 and 0.506, p =
0.005 and <0.001, espec i ely). A 500 Hz,
signi ican co ela ions appea ed a 3 mon hs (PTA
= 0.001 × Dmax + 13.373, R² = 0.213, p = 0.005)
and 6 mon hs (PTA = 0.003 × Dmax + 14.059, R² =
0.531, p < 0.001). Fo 1000 Hz, h esholds
co ela ed wi h Dmax a 3 mon hs (PTA = 0.002 ×
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Bane jee e al. In e na ional Jou nal o Cu en Pha maceu ical Re iew and Resea ch
669
Dmax + 18.983, R² = 0.266, p = 0.001) and 6
mon hs (R² = 0.57, p < 0.001).
Discussion
Ou s udy assessed cochlea -spa ing adia ion
he apy in head and neck ca cinoma pa ien s
unde going de ini i e chemo adia ion. We
obse ed signi ican inc eases in hea ing h esholds
o e ime, pa icula ly a lowe equencies, which
aligns wi h indings om p e ious esea ch [1,2].
Linea eg ession analysis e ealed a dose-
dependen ela ionship be ween cochlea adia ion
dose (Dmax) and hea ing h esholds, consis en
wi h s udies ha iden i ied signi ican ac o s
in luencing hea ing h eshold shi s in pa ien s
ecei ing chemo adio he apy [3,4]. Ki oh e al.
epo ed g ea e h eshold inc emen s a highe
equencies, which is ele an when conside ing
iming and equency-speci ic moni o ing [5].
Cochlea-spa ing echniques ha e been shown o
educe hea ing loss wi hou comp omising umo
con ol, as demons a ed in op imized IMRT
planning s udies [6,7]. In con as , o he s udies
epo ed ad e se cochlea e ec s when
con en ional adia ion echniques we e used,
emphasizing he impo ance o p ecise ea men
planning [8,9]. Collec i ely, ou indings
co obo a e exis ing li e a u e on he de imen al
e ec s o chemo adia ion on hea ing unc ion. The
obse ed dose-dependen ela ionship unde sco es
he necessi y o me iculous cochlea -spa ing
s a egies o mi iga e o o oxici y. Fu u e esea ch
should ocus on e ining hese echniques and
explo ing in e en ions o p ese e hea ing in his
pa ien popula ion [10].
Conclusion
Cochlea -spa ing adia ion he apy in pa ien s wi h
head and neck ca cinoma unde going de ini i e
chemo adia ion e ec i ely p ese es hea ing
unc ion, pa icula ly a highe equencies, while
s ill allowing op imal umo dose deli e y.
Ou s udy demons a ed ha hea ing h esholds
g adually inc ease o e ime, wi h he mos
signi ican changes obse ed a lowe equencies
and a 3 o 6 mon hs pos - ea men . Impo an ly,
hea ing loss was ound o be dose-dependen ,
co ela ing wi h he maximum cochlea adia ion
dose (Dmax), and highligh ing he c i ical ole o
me iculous ea men planning.
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