Jou nal P e-p oo
Con ac X- ay B achy he apy (CXB) as a boos he apy a e
neoadju an (chemo) adia ion in high- isk locally ad anced ec al
cance
Ngu Wah Than MRCP , D. Ma k P i cha d FRCP ,
Da id M. Hughes PhD , Ca ie. A. Duckwo h PhD ,
Helen Wong PhD , Muneeb Ul Haq MBBS ,
Raja am S ipadam FRCR , A hu Sun Myin FRCR
PII: S0360-3016(24)03720-9
DOI: h ps://doi.o g/10.1016/j.ij obp.2024.11.113
Re e ence: ROB 29144
To appea in: In e na ional Jou nal o Radia ion Oncology, Biology, Physics
Recei ed da e: 16 Augus 2024
Re ised da e: 4 No embe 2024
Accep ed da e: 29 No embe 2024
Please ci e his a icle as: Ngu Wah Than MRCP , D. Ma k P i cha d FRCP , Da id M. Hughes PhD ,
Ca ie. A. Duckwo h PhD , Helen Wong PhD , Muneeb Ul Haq MBBS , Raja am S ipadam FRCR ,
A hu Sun Myin FRCR , Con ac X- ay B achy he apy (CXB) as a boos he apy a e neoadju an
(chemo) adia ion in high- isk locally ad anced ec al cance , In e na ional Jou nal o Radia ion Oncol-
ogy, Biology, Physics (2024), doi: h ps://doi.o g/10.1016/j.ij obp.2024.11.113
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1
Con ac X- ay B achy he apy (CXB) as a boos he apy a e neoadju an
(chemo) adia ion in high- isk locally ad anced ec al cance
Sho unning i le: Con ac adia ion in high- isk ec al cance
Ngu Wah Than MRCP1,2, D. Ma k P i cha d FRCP1, Da id M. Hughes PhD3, Ca ie. A. Duckwo h PhD1,
Helen Wong PhD2, Muneeb Ul Haq MBBS1,2, Raja am S ipadam FRCR2, A hu Sun Myin FRCR1,2
1Depa men o Molecula and Clinical Cance Medicine, Ins i u e o Sys ems, Molecula and
In eg a i e Biology, The Uni e si y o Li e pool, L69 3GE, Uni ed Kingdom
2The Cla e b idge Cance Cen e NHS Founda ion T us , 65 Pemb oke Place, Li e pool, L7 8YA,
Uni ed Kingdom
3Depa men o Heal h Da a Science, Ins i u e o Popula ion Heal h, The Uni e si y o Li e pool, L7
3EA, Uni ed Kingdom
Co esponding Au ho :
P o esso A hu Sun Myin , sun.myin @nhs.ne
Au ho Responsible o S a is ical Analysis:
D Da id M. Hughes, Da id.Hughes@li e pool.ac.uk
Con lic s o in e es : None
Funding s a emen :
The i s au ho 's wo k was unded by he Eu opean Union’s Ho izon 2020 esea ch and inno a ion
p og amme, Ma ie Skłodowska-Cu ie g an ag eemen numbe 857894—CAST.
Da a a ailabili y s a emen
Resea ch da a a e s o ed in he ins i u ional eposi o y and anonymised da a will be sha ed upon
eques o he co esponding au ho .
Acknowledgemen
This p ojec was unded by he Eu opean Union’s Ho izon 2020 esea ch and inno a ion p og amme,
Ma ie Skłodowska-Cu ie g an ag eemen numbe 857894—CAST.
2
Abs ac
Backg ound and pu pose
Radical su ge y ollowing neoadju an he apy is he s anda d o ca e o locally ad anced ec al
cance . A Con ac X- ay B achy he apy (CXB) boos can al e na i ely be used o ea esidual disease
pos neoadju an (chemo) adia ion, especially in pa ien s who a e no sui able o o do no wish o
ha e su ge y. I s ole has mos ly been s udied o da e in low o in e media e- isk pa ien s. We ha e
now e alua ed he u ili y o CXB-boos in high- isk ec al cance s a e hei umou s ha e been
signi ican ly downs aged by neoadju an (chemo) adia ion.
Ma e ials and me hods
Oncological ou comes and ea men ole abili y we e e alua ed in 328 pa ien s based on ec al
cance ea men isk s a i ica ion: low/in e media e isk (cT1-3ab, N0-1, M0, no ex amu al
in asion (EMVI), meso ec al ascia (MRF) in ol emen >1mm) and high- isk (cT3cd-4/N2, M0,
MRF≤1mm and/o EMVI posi i e).
Resul s
Wi h median ollow-up o 33(IQR:15-54) mon hs and median age o 73(IQR:62-80) yea s, no
signi ican di e ences we e ound be ween low/in e media e and high- isk g oups in clinical
comple e esponse (78% s 73%, p=0.32), local eg ow h (16.6% s 22.4%, p=0.41), nodal (1.8% s
5.8%, p=0.051) o egional (1.3% s 2.9%, p=0.33) elapse, o pos - adia ion oxici ies (p=0.16).
Howe e , he high- isk g oup had a highe dis an elapse a e (21.2% s 10.7%, p=0.01), wi h no
signi ican di e ences in 3-yea o gan p ese a ion (80% s 87%, p=0.25), 5-yea disease- ee (DFS)
(62% s 64%, p=0.46), o o e all (OS) su i als (67% s 64%, p=0.88). Longe ea men ime,
ea men gap >24 weeks be ween he apies, and adminis a ion o a highe han s anda d CXB dose
we e newly iden i ied ac o s ha nega i ely impac ed ou comes.
Conclusions
3
High- isk ec al cance pa ien s ea ed wi h CXB-boos had mo e dis an elapses, bu compa able
loco egional umou con ol, o gan p ese a ion, DFS and OS o lowe - isk pa ien s, wi h accep able
oxici ies. CXB-boos is he e o e a iable op ion o selec ed high- isk ec al cance pa ien s. Timely
eassessmen , p omp e e al, and CXB dose op imisa ion a e c ucial o imp o ing ou comes.
Sho unning i le: Con ac adio he apy in high- isk ec al cance
4
In oduc ion
Cu en guidelines o managing locally ad anced ec al cance ecommend s a ing wi h
neoadju an ea men , including o al neoadju an he apy, (chemo) adia ion, o immuno he apy
based on umou s age and molecula misma ch epai (MMR) s a us, ollowed by adical o al
meso ec al excision (TME) [1-3]. This mul i-modali y app oach educes pel ic ecu ence (2.4-15%)
and imp o es 5-yea o e all su i al (64-87%) [4-6]. Howe e , hese bene i s come a he cos o
pos -ope a i e complica ions [7], s oma o ma ion, and unc ional impai men o pel ic o gans [8, 9].
O e he pas wo decades, o gan-p ese ing s a egies, including local excisions and adia ion dose-
escala ion ea men s a e neoadju an he apy, ha e been adop ed o a oid complica ions ela ed
o gene al anaes hesia and su ge y [10], and o espec pa ien s' p e e ences o a oid ex i pa i e
su ge y [11]. Published e idence epo s ha non-su gical ea men achie es long- e m o gan
p ese a ion (59-97%), disease- ee su i al (61-94%), and o e all su i al (71-91%) [12-16].
The UK Na ional Ins i u e o Heal h and Ca e Excellence (NICE) cu en ly ecommends he use o
con ac X- ay b achy he apy (CXB) only o high su gical isk pa ien s who ha e ea ly-s age ec al
cance , emphasising i s sa e y and e icacy o hese cases. Howe e i is no cu en ly ecommended
o locally ad anced umou s, unless in a esea ch con ex [17, 18]. Howe e , in ou ine clinical
p ac ice, CXB is used o a ious indica ions wi h in o med pa ien consen , due o he highe bowel
cance incidence in he elde ly [19], inc eased como bidi ies wi h ad ancing age [20], and pa ien s’
p e e ences o a oid colos omy [11]. CXB can be used alone o as adju an he apy a e local
excision in s age-I ec al cance , as a boos combined wi h (chemo) adia ion in ope able/mo e
ad anced umou s, and also as an al e na i e sal age op ion o luminal eg ow h a e wa ch-and-
wai su eillance [21-24].
Magne ic Resonance Imaging (MRI) is he s anda d o ini ial and pos - he apy ( e)s aging and
de e mining ea men isk ca ego ies o guide neoadju an he apy in ec al cance managemen
[25]. O e ecen yea s, he de ini ion o high- isk ea u es in locally ad anced ec al cance has
5
e ol ed [26], wi h low- isk umou s cu en ly being de ined as cT1-3abN0M0, umou o meso ec al
ec al ascia (MRF) dis ance >1mm and no ex amu al enous in asion(EMVI); in e media e- isk as
cT1-3abN1-2M0, MRF >1mm, no EMVI; and high- isk as cT3cd-4anyNM0, anycTN2M0, MRF ≤1mm,
and/o p esence o EMVI [2, 3].
Nume ous s udies, including wo andomised con olled ials, ha e in es iga ed he e icacy o CXB
as a boos he apy o esidual disease ollowing neoadju an (chemo) adia ion, bu hese ha e
p ima ily ocused on low and in e media e- isk ec al cance s [23, 27-31]. The ongoing OPAXX phase
II s udy is cu en ly ec ui ing pa ien s o assess he one-yea o gan p ese a ion a e a e a CXB
boos o good esponde s (small esidual/nea Comple e Response (nCR)) a e neoadju an
ea men in in e media e/high- isk pa ien s [32]. Howe e , comp ehensi e epo s abou he
e icacy o CXB boos in combina ion wi h (chemo) adia ion in his con ex a e cu en ly lacking.
We he e o e conduc ed his s udy o in es iga e he oncological ou comes o CXB-boos he apy
a e signi ican downs aging wi h neoadju an (chemo) adia ion in high- isk e sus
low/in e media e- isk ec al cance pa ien s using MRI-based ea men isk s a i ica ion along wi h
he impac o pa ien - ela ed ac o s, umou cha ac e is ics, and ea men on oncological
ou comes and ole abili y.
Ma e ials and me hods
Pa ien selec ion
Ins i u ional audi app o al was ob ained on 3 d May 2022 o a e ospec i e e iew o all sequen ial
pa ien s who had unde gone bo h (chemo) adia ion and CXB wi h cu a i e in en a ou cen e om
2008 o 2019. Pa ien demog aphics, umou cha ac e is ics, de ailed MRI s aging epo s, ea men
de ails, and ou come da a we e en e ed in o an ins i u ional CXB da abase sys em and subsequen ly
analysed.
Neoadju an ea men
6
Neoadju an ex e nal beam adia ion (EBRT) was adminis e ed in one o h ee egimens:
chemo adia ion (45-54Gy/25-30 ac ions/5-6 weeks), o long-cou se (40-50Gy/20-25 ac ions/4-5
weeks), o sho -cou se (25Gy/5 ac ions/1 week) adio he apy alone, chosen based on pa ien
pe o mance s a us and como bidi ies. Ini ially, con o mal 3-dimensional adia ion (3D-CRT) was he
p ima y echnique used, wi h a ansi ion o In ensi y Modula ed Radia ion The apy (IMRT) a e
2013. (Neo)adju an chemo he apy was no ou inely adminis e ed be o e o ollowing
adio he apy. Pa ien s we e eassessed using digi al ec al examina ion (DRE), sigmoidoscopy,
and/o es aging MRI scans. Those who had signi ican downs aging (small esidual disease/nea
clinical Comple e Response (nCR)) a e neoadju an he apy we e e e ed o conside a ion o CXB.
(Supplemen a y igu e 1)
Con ac X- ay B achy he apy (CXB) as a boos he apy
Pa ien s e e ed om local colo ec al cance mul idisciplina y eams (MDTs) ac oss he Uni ed
Kingdom we e e iewed be o e s a ing CXB a he CXB MDT mee ing. Sui abili y o adminis a ion
o CXB wi h cu a i e in en was assessed by digi al ec al examina ion (DRE), iden i ying small,
mobile o sligh ly e he ed esidual disease (≤3 cm) loca ed wi hin 10 cm o he anal e ge.
Addi ionally, pos -neoadju an sigmoidoscopy and/o MRI indings had o show signi ican umou
downs aging and downsizing compa ed o p e- ea men imaging, wi h no e idence o nodal
in ol emen . T ea men in en we e discussed and pa ien s we e in o med ha CXB is no he
s anda d ca e in ou coun y and ha su ge y may ha e o be econside ed i esidual umou o
eg ow h occu ed ollowing ea men . All pa ien s we e eques ed o sign a consen o m be o e
ea men ini ia ion. CXB was deli e ed on an ou pa ien basis using he Papillon-50© machine
(50kVp X- ays, HVL 0.64 mm Al, 2.7 mA; A iane, Al e on, UK). The adia ion dose o 20-30Gy was
adminis e ed a each ac ion wo weeks apa ia a ec al ea men applica o (sizes 30, 25, o 22
mm) a ocal sou ce-su ace dis ances o 29, 32, o 38 mm, espec i ely. A s anda d dose o 90Gy
( ec al mucosa su ace dose) was deli e ed in 3 ac ions o e 4 weeks. A ou h 20Gy dose ( o al
7
110Gy) was adminis e ed o selec ed pa ien s who had minimal isible and/ palpable umou s s ill
p esen a e he hi d ac ion.
Follow-up
Pa ien s achie ing comple e o nea -clinical esponses (cCR/nCR) a 8-12 weeks pos - ea men we e
egula ly moni o ed. Follow-up included DRE, lexible sigmoidoscopy/ igid ec oscopy al e na ely a
he pa ien ’s local colo ec al cen e and ou cen e (i he pa ien s we e p epa ed o a end egula
appoin men s a ou cen e), wi h MRI scans e e y 12 weeks o he i s 2 yea s and e e y 6 mon hs
in he hi d yea . Only endoscopic examina ions we e pe o med in he ou h and i h yea s.
Pa ien s who did no achie e cCR, which was con i med by he iple assessmen (DRE, endoscopy,
and MRI) wi h/wi hou his ological con i ma ion, by 24 weeks o who expe ienced local eg ow h
du ing su eillance we e e e ed o sal age su ge y i hey ag eed and we e deemed sui able.
Ou come measu es
This s udy assessed oncological ou comes ac oss he en i e coho and wo isk g oups based on
ea men isk s a i ica ion: low/in e media e isk (cT1-3ab, N0-1, M0, no EMVI, MRF > 1mm) and
high- isk (cT3cd-4/N2, M0, MRF ≤ 1mm and/o EMVI posi i e). cN2 cases we e excluded om he
in e media e- isk g oup due o unspeci ied ex a-nodal o in a-nodal de ails in MRI epo s. P ima y
endpoin s included cCR, a es o local, nodal, egional, and dis an elapses, o gan p ese a ion a e,
disease- ee su i al (DFS), and o e all su i al (OS). Local eg ow h was de ined as luminal
ecu ence a he si e o he o iginal umou , while nodal elapse e e ed o ecu ence limi ed o
he meso ec al o pel ic lymph nodes. Regional elapse was de ined as ecu ence in a nea by
s uc u e ou side he ec um, such as he aginal wall o p esac al space. The o gan p ese a ion
a e was de ined as he absence o ansabdominal esec ion, and he absence o loco egional
eg ow h unless sal aged by ansanal R0 (mic oscopically clea ma gin) excisions. DFS was
calcula ed om he las ea men o loco egional ecu ence pos -R0/R1 (mic oscopically posi i e
ma gin) esec ion, non-sal ageable local eg ow h/R2 (mac oscopically posi i e ma gin) esec ion
8
pos -sal age su ge y, he occu ence o second p ima y/dis an me as asis, o las ollow-up. OS was
measu ed om he i s da e o diagnosis o he las da e o da a e iew o dea h om any cause.
Seconda y ou comes included e alua ing he adia ion oxici ies using Common Te minology C i e ia
o Ad e se E en s (CTCAE) c i e ia e sion 5.0 [33] and he in luence o pa ien , umou , and
ea men ac o s on local umou con ol, dis an elapse, and su i als.
S a is ical analysis
Quan i a i e da a a e p esen ed as medians wi h in e qua ile ange (IQR) o means wi h s anda d
de ia ion (SD), while ca ego ical da a a e p esen ed as coun s and pe cen ages. Ca ego ical a iables
we e compa ed using he χ2 es , wi h Fishe ’s exac es ( wo- ailed) applied when necessa y.
Con inuous a iables we e compa ed using he Mann-Whi ney U es due o non-no mal
dis ibu ion. G oup su i al di e ences we e examined using Kaplan-Meie cu es and Log- ank es s
we e used o s a is ical assessmen . Associa ions be ween pa ien , umou , and ea men
cha ac e is ics and su i al isks we e analysed u ilising Cox p opo ional haza d models. Logis ic
eg ession was employed o e alua e bina y ma gin ou comes. Va iables wi h p≤0.2 in he
uni a iable analyses we e included in he mul i a iable analyses. A p- alue <0.05 was conside ed
s a is ically signi ican . All s a is ical analyses we e conduc ed using R e sion 4.4.0.
Resul s
A o al o 402 consecu i e pa ien s who had been ea ed wi h (chemo) adia ion ollowed by CXB
boos he apy we e ini ially iden i ied om he ins i u ional da abase (2008-2019). A e excluding
pa ien s wi h unknown s aging (Tx/Nx) (n=3), hose s aged solely by CT scan (n=16) (because o i s
lowe sensi i i y and speci ici y o umou s aging compa ed wi h MRI [34]), indi iduals ea ed
pallia i ely (n=17), cases wi h p io local excision (n=1), unde -dosed CXB ecipien s o a ious
easons (30-60Gy) (n=18), and hose los o ollow-up (n=19), 328 pa ien s we e eligible o analysis.
The s udy p o ile is ou lined in Figu e 1.
15
E hics boa d app o al
As his s udy was a e ospec i e obse a ional s udy, i was app o ed by he ins i u ional audi
commi ee on 3 d May 2022, and no e hical app o al was equi ed.
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23
Lis o igu es
Low/in e media e isk
n=224
High isk
n=104
Figu e 1: S udy p o ile
1. Compa e oncological and clinical ou comes
2. In luence o pa ien , umou , and ea men
ac o s on oncological ou comes
Included cases
n=328
Excluded cases
Los ollow-up a e las ea men =19
Pallia i e in en =17
Pos -excision case=1
CXB unde -dosed (30-60Gy) cases=18
Tx/Nx cases=3
S aging using CT scan=16
Consecu i ely ea ed pa ien s CXB boos
a e (chemo) adia ion (2008-2019)
n=402
24
Figu e 2: Flow diag am illus a ing he oncological ou comes o he wo isk g oups
CXB boos a e
(chemo) adia ion
n=328
Low-in e media e
isk
n=224
High isk
n=104
Ini ial cCR
n=175(78%)
Residual
disease
n=49(22%)
Ini ial cCR
n=76(73%)
00
Residual
disease
n=28(27%)
Local eg ow h
n=29/175(16.6%)
APER=15
Ha mann’s=
1
EMR=1
BSC=12
Nodal elapse
n=3
TEMS=3
LAR=3
APER=11
Exen e a ion=2
BSC=20
cCR: clinical Comple e Response, APER; Abdomino Pe i oneal Excision o Rec um, Ha mann’s: Ha mann’s ope a ion, LAR: Low An e io Resec ion, Exen e a ion: Pel ic
Exen e a ion, EMR: Endoscopic Mucosal Resec ion, TEMS: T ansanal Endoscopic Mic osu ge y, SBRT: S e eo ac ic Body Radio he apy, BSC: Bes Suppo i e Ca e
Dis an
elapse
n=5
Dis an
elapse
n=11
Dis an
elapse
n=3
Dis an
elapse
n=4
Dis an
elapse=1
Regional
elapse=1
APER=1
SBRT=1
BSC=1
Local eg ow h
n=17/76(22.4%)
Dis an
elapse
n=4
APER=9
Ha mann’s=1
TEMS=1
BSC=6
Dis an
elapse
n=1
Dis an
elapse
n=4
Nodal elapse
n=3
Exen e a ion=
1
BSC=2
APER=13
Ha mann’s=1
TEMS=1
BSC=13
Dis an
elapse=7
Nodal elapse=1
Regional
elapse=2
Dis an
elapse
n=4
Nodal elapse
n=3
Regional
elapse=1
Dis an
elapse
n=2
Regional
elapse=2
Nodal elapse
n=1
31
Mean umou size a ime o CXB (cm)
1.7±0.9
1.6±0.9
1.8±1.1
0.19ǂ
Tumou size g oup
a CXB
≤3cm
>3-5cm
No eco ded
315(96)
12(3.7)
1(0.3)
218(97)
6(3)
0(0)
97(93)
6(6)
1(1)
0.16¥
Dis ance om anal
e ge
3-≤6cm
>6-12cm
No eco ded
226(69)
85(26)
17(5)
152(68)
59(26)
13(6)
74(71)
26(25)
4(4)
0.72¥
EBRT egimen
Sho cou se
Long cou se
Chemo adia ion
54(16.5)
59(18.0)
215(65.5)
48(21.4)
44(19.6)
132(59)
6(5.8)
15(14.4)
83(79.8)
<0.001¥
Res aging wi h MRI
Yes
No
No eco ded
201(61)
107(33)
20(6)
85(38)
123(55)
16(7)
78(75)
22(21)
4(4)
0.001¥
S age a e
(chemo) adia ion
yT0,yN0,yM0
yT1/2,yN0,yM0
yT2/3,yN0,yM0
yT3/4,yN0,yM0
Unknown
41(12.5)
120(36.5)
34(10)
6(2)
127 (39)
20(9)
84(37)
17(8)
2(1)
101(45)
21(20)
36(35)
17(16)
4(4)
26(25)
0.02¥
T ea men gap ime
be ween EBRT and
CXB
<12 weeks
12-24 weeks
>24-48 weeks
155(47.3)
132(40.2)
41(12.5)
115(51.3)
85(38)
24(10.7)
40(39)
47(45)
17(16)
0.07¥
O e all ea men
ime
Con en ional
Uncon en ional
188(57.3)
140(42.7)
130(58)
94(42)
58(55.8)
46(44.2)
0.70¥
CXB o al dose
80-90Gy
110Gy
224(68.3)
104(31.7)
152(68)
72(32)
72(69)
32(31)
0.80¥
To al CXB
ea men ime
S anda d (4-6 weeks)
Uncon en ional (>6-9 weeks)
216(66)
112(34)
149(66.5)
75(33.5)
67(64)
37(36)
0.71¥
IQR: In e qua ile Range, WHO: Wo ld Heal h O ganiza ion, EBRT: Ex e nal Beam Radia ion, CXB: Con ac X- ay
B achy he apy, MRI: Magne ic Resonance Imaging, ǂ= Mann-Whi ney U es , ¥= χ2 es
32
Table 2: Oncological and clinical ou comes o he whole coho and isk g oup s udies
Ou come
To al
n=328(%)
Risk s a i ica ion
Low/in e media e
n=224(%)
High
n=104(%)
P alue
(χ2 es )
Nea /comple e Clinical Response (n/cCR)
251(76.5)
175(78)
76(73)
0.32
Residual disease
77(23.5)
49(22)
28(27)
Numbe o pa ien s who unde wen sal age
su ge y and ou comes
34/77 (44)
R0=27
R1=6
R2=1
19/49(39)
R0=18
R1=1
15/28 (54)
R0=9
R1=5
R2=1
Local eg ow h
46/251(18.3)
29/175(16.6)
17/76(22.4)
0.41
Numbe o pa ien s who unde wen sal age
su ge y and ou comes
28/46 (61)
R0=22
R1=5
R2=1
17/29 (59)
R0=14
R1=3
11/17 (65)
R0=8
R1=2
R2=1
Nodal elapse
10(3.0)
4(1.8)
6(5.8)
0.051
Regional elapse
6(1.8)
3(1.3)
3(2.9)
0.33
Numbe o pa ien s (bo h nodal and egional)
who unde wen sal age su ge y and ou comes
7/16 (44)
R0=4
R1=2
CR=1
5/7 (71)
R0=2
R1=2
(SBRT – CR)
2/9 (22)
R0=2
Dis an elapse
46(14)
24(10.7)
22(21.2)
0.01
Numbe o pa ien s who unde wen sal age
su ge y and ou comes
6/46 (13)
All CR
2/24 (8)
Lung esec ion=2
4/22 (18)
Lung esec ion=3
Li e esec ion=1
To al incidence o adia ion oxici ies
96(29.3)
64(28.6)
32(30.8)
0.16
Acu e p oc i is (e a ic bowel, pain)
G ade 1-2
G ade 3
28(8.5)
0(0)
20(9)
0(0)
8(7.7)
(0)
La e ec al bleeding
G ade 1/2
G ade 3
58(17.7)
3(0.9)
35(15.6)3(1.4)
23(22.3)
0(0)
Faecal incon inence
G ade 1-2
G ade 3
4(1.2)
0(0)
3(1)
0(0)
1(0.9)
0(0)
S ic u e
G ade 1-2
G ade 3
3(0.9)
0(0)
3(3.7)
0(0)
0(0)
0(0)
R0= mic oscopically nega i e ma gin esec ion, R1= mic oscopically posi i e ma gin esec ion, R2= mac oscopically posi i e
ma gin esec ion, SBRT= S e eo ac ic Body Radio he apy, CR= Comple e Response
33
Supplemen a y Table on Gene alizabili y o S udy Popula ion(s)
Condi ion
Desc ip ion
Disease, p oblem, o
condi ion unde
in es iga ion
High- isk locally ad anced ec al adenoca cinoma
Rele an conside a ions o
disease, p oblem, o
condi ion in ela ion o:
No e any ele an conside a ions in boxes below:
Sex and gende
In 2019, 142,462 cases o colon and ec um cance we e
epo ed in he UK: 75,581 among males and 66,881 among
emales. The incidence a e was 36 pe 100,000 s anda d
popula ion and was 42 pe 100,000 males and 32 pe 100,000
emales.
Age
Incidence a es o bowel cance in he UK a e highes in
people aged 85 o 89 (2017-2019). Each yea mo e han 4 in
10 (43%) o all new bowel cance cases in he UK a e
diagnosed in people aged 75 and o e (2017-2019).
Race o e hnic
g oup
Incidence a es o bowel cance a e lowe in he Asian and
Black e hnic g oups, and in people o mixed o mul iple
e hnici y, compa ed wi h he Whi e e hnic g oup, in England
(2013-2017).
Geog aphy
La ge geog aphical a ia ions in incidence and mo ali y a es
a e obse ed. The incidence a es a e highes in Eu ope and
Aus alia and New Zealand, and he mo ali y a es a e highes
in Eas e n Eu ope.
O he
conside a ions
S udy
Desc ip ion
O e all assessmen o
gene alizabili y o he
s udy popula ion
This s udy was conduc ed in an olde coho wi h a median age
o 73(IQR:62-80) yea s, who had high- isk locally ad anced
ec al cance . 73% o pa ien s we e male. Da a on e hnici y
was no a ailable, al hough he majo i y we e whi e B i ish. All
pa ien s we e om he Uni ed Kingdom. The ea men p o ocol
used in his s udy is applicable o all popula ions.
