ORIGINAL RESEARCH
Wo king owa ds a consensus on he oncological
app oach o b eak h ough pain: a Delphi su ey o
Spanish expe s
This a icle was published in he ollowing Do e P ess jou nal:
Jou nal o Pain Resea ch
Ca los Camps He e o
1
An onio An ón To es
2
Juan Jesús C uz-He nández
3
Al edo Ca a o
4
Manuel Cons enla
5
Edua do Díaz-Rubio
6
Ma ga i a Feyjoo Saus
7
Jesus Ga cia-Foncillas
8
Pe e Gascón
9
Vicen e Guillem
10
1
Je e de Se icio de Oncología Médica,
Conso cio Hospi al Gene al
Uni e si a io, Valencia, Spain;
2
Je e del
Se icio de Oncología Médica, Hospi al
Uni e si a io Miguel Se e , Za agoza,
Spain;
3
Je e del Se icio de Oncología
Médica, Hospi al Uni e si a io De
Salamanca-IBSAL, Salamanca, Spain;
4
Je e
del Se icio de Oncología Médica,
Hospi al Uni e si a io Ramón y Cajal,
Mad id, Spain;
5
Je e de Se icio de
Oncología, Complejo Hospi ala io
Uni e si a io de Pon e ed a, Pon e ed a,
Spain;
6
Je e del Se icio de Oncología
Médica, Hospi al Uni e si a io Clínico
San Ca los, Mad id, Spain;
7
Je e del
Se icio de Oncología Médica, Hospi al
La Mo aleja, Mad id, Spain;
8
Je e de
Se icio de Oncología Médica, Hospi al
Uni e si a io “Fundación Jiménez Díaz”,
Mad id, Spain;
9
Je e del Se icio de
Oncología Médica, Hospi al Clínic,
IDIBAPS, Uni e sidad de Ba celona,
Ba celona, Spain;
10
Je e del Se icio de
Oncología Médica, Ins i u o Valenciano
de Oncología, Valencia, Spain
Pu pose: The e is a lack o s anda ds o he diagnosis, assessmen and managemen o
b eak h ough cance pain (BTcP). La Fundación ECO ( he Founda ion o Excellence and
Quali y in Oncology) commissioned a s udy o es ablish a consensus and lay he ounda ions
o he app op ia e managemen o BTcP in oncology pa ien s.
Pa ien s and me hods: A modified Delphi su ey comp ising wo ounds was used o
ga he and analyze da a, which was conduc ed o e he In e ne . Each s a emen ha eached
a consensus wi h he esponden s was defined as a median consensus sco e (MED) o ≥7, and
ag eemen among panelis s as an in e qua ile ange (IQR) o ≤3.
Resul s: In o al, 69 medical oncologis s esponded, wi h a b oad consensus ha BTcP implied
exace ba ions o high-in ensi y pain, as opposed o mode a e pain. Fu he mo e, hey concu ed
ha app op ia e diagnos ic equipmen is needed, and ha apid-onse en anyl o mula ions
should be he p e e ed ea men o BTcP managemen . The panelis s ag eed ha a lack o
app op ia e in o ma ion and aining o a end o pa ien s, as well as limi ed pa ien isi a ion
igh s, we e ba ie s o e ec i e BTcP managemen . Rega ding gaps in de ec ed knowledge,
he panelis s we e unsu e o he measu es necessa y o assess he bu den o he disease on he
pa ien ’s quali y o li e and associa ed medica ion cos s. Alongside his, he e was a lack o
awa eness o he echnical specifics o he di e en o mula ions o apid-onse en anyl.
Conclusion: These esul s ep esen he cu en s a us o BTcP managemen . They may
in o m ecommenda ions and p o ide a amewo k o u u e esea ch.
Keywo ds: b eak h ough pain, apid-onse opioids, en anyl, medical oncology, pain
managemen
In oduc ion
B eak h ough cance pain (BTcP) managemen is one o he mos challenging
p oblems associa ed wi h cance pain, and has been linked o a nega i e impac
on he pa ien ’s quali y o li e (QoL) and abili y o unc ion. I can lead o highe
le els o dep ession and anxie y, poo e p ognos ic on u u e pain elie , and an
inc eased bu den o amilies and heal h se ices.
1–6
The p e alence o BTcP has been epo ed o ange om 19% o 95%, depend-
ing on he BTP defini ion and he clinical se ing.
1,3,5,7
The In e na ional
Associa ion o he S udy o Pain (IASP) es ima es ha be ween one hal and wo
hi ds o pa ien s wi h ch onic cance - ela ed pain expe ience BTcP episodes.
Despi e i s p e alence, BTcP emains an unde diagnosed and unde ea ed
condi ion. The easons o his a e p obably mul i ac o ial, esul ing om a lack
Co espondence: Ca los Camps He e o
Conso cio Hospi al Gene al Uni e si a io,
A da. de las T es C uces, s/n; 46014
Valencia, Spain
Tel +34 63 622 4107
Email camps_ca @g a.es
Jou nal o Pain Resea ch Do ep ess
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o o ficial defini ion, and unjus ified a i udes and miscon-
cep ions held by heal hca e p o essionals and pa ien s
ega ding opioids.
5,9–12
Despi e in e na ional e o s, he e is s ill no one uni-
e sally accep ed BTcP defini ion.
13,14
O e all, BTcP can
be conside ed as a ele an ansi o y inc ease in pain.
Howe e , he e is con o e sy ega ding he in ensi y o
his pain and he pa ien ’s basal pain (absence o BTcP,
BTcP e ec i ely ea ed wi h opioids o uncon olled
BTcP).
15–17
No wi hs anding he p oli e a ion o guidelines add es-
sing pain in cance pa ien s,
6–8,18,19
he e is no consensus
on BTcP managemen , and ecommenda ions a e he e o-
genous, which is p e en ing he es ablishmen o an ade-
qua ely analgesic app oach.
Classically, ea men op ions in ol e he op imiza ion
o he scheduled backg ound analgesia and supplemen ing
i wi h “ escue”medica ion when BTcP occu s.
18
Sho -
ac ing opioids (SAOs) —immedia e- elease o mula ions
o mo phine—we e p e iously conside ed he s anda d o
ca e. Howe e , ecen e idence shows ha apid-onse
opioids (ROOs) p o ide sa e and e ec i e BTcP manage-
men . ROO o mula ions a e cha ac e ized by a apid onse
and sho du a ion o ac ion, consis en wi h he na u e o
BTcP episodes (acu e)
7,14,17,20
and he apid esolu ion o
pain equi ed by hese pa ien s.
15
The pha macokine ics and ole abili y p ofile o apid-
ac ing en anyl p oduc s ende hem sui able o mana-
ging he acu e, se e e pain in ensi y ha gene ally cha -
ac e izes BTcP episodes.
19,21,22
Addi ionally, indi idualized he apy is made u he
possible due o he wide ange o di e en apid-onse
en anyl o mula ions and p epa a ions a ailable.
Howe e , he absence o comp ehensi e compa a i e ials
means physicians mus ely on hei unde s anding and
expe ience when p esc ibing he medica ion. This is
impo an o de e mine he mos e ec i e and bes - ole -
a ed o mula ions o each pa ien .
16,17,20
In ligh o he abo e, physicians should be awa e ha
apid-onse en anyl o mula ions a e no bioequi alen (as
hey ha e subs an ial p ac ical di e ences); no a e hey
in e changeable. Each o mula ion will ha e a di e en
ype o i a ion, depending on he needs o he pa ien .
17
In clinical p ac ice, he success ul managemen o
BTcP equi es ca e ul assessmen , ongoing eassessmen ,
and a ea men ha is ailo ed o he indi idual pa ien .
The ea men should also conside he ype and cause o
he BTcP, as well as pa ien p e e ences.
6,23
Wi hin his con ex , he Founda ion o Excellence and
Quali y in Oncology (ECO) commissioned a s udy o
es ablish a consensus. This could subsequen ly be used o
lay he ounda ions o he app op ia e managemen o
BTP (se e ely in ense pain) in cance pa ien s. The goal
o he s udy was o achie e a consensus among medical
oncologis s on a clinical app oach owa ds he diagnos ic
e alua ion and app op ia e pha macological managemen
o pa ien s wi h BTcP, specifically wi h apid-onse en a-
nyl o mula ions.
Ma e ials and me hods
This s udy was ca ied ou ga he ing and analyzing he
opinion o expe using he Delphi me hod. In Spain his
ype o s udy is no included among hose equi ing
Resea ch E hics Commi ees (RECs) app o al o w i en
consen .
A Scien ific Commi ee (SC) was appoin ed, comp is-
ing h ee membe s om he Founda ion o Excellence and
Quali y in Oncology and wo suppo me hodologis s. The
SC de eloped he ques ions o he fi s ound, s uc u ed
he ques ionnai e, se up he online ques ionnai e in o he
websi e c ea ed o he s udy, unde ook s a is ical analysis
o he da a, p oduced in e im documen s and o e saw he
p ocess’s gene al managemen .
The expe panel membe s, selec ed by he SC,
included 71 Spanish oncology expe s who we e in i ed
o pa icipa e in he consensus p ocess h ough a modified
In e ne -based Delphi su ey made up o wo ounds.
Expe s we e iden ified om a selec ion o physicians
specializing in medical oncology, and each possessed
documen ed clinical expe ise in cance managemen a
e e al hospi als. The Delphi pa icipan s we e loca ed in
geog aphically di e se pa s o Spain, and we e sen an
email in i ing hem o ake pa in he s udy, as well as a
link o access he ques ionnai e on he su ey websi e.
The ques ionnai e
A selec ion o 50 s a emen s we e de eloped, each o
which was ele an o he diagnosis, assessmen and man-
agemen o BTcP, and based on con o e sies ound in
bo h clinical p ac ice and exis ing li e a u e.
15,24–26
The
ques ionnai e was adminis e ed in Spanish. The pu pose
was o each a consensus on ques ions a ising om: a) The
defini ion and assessmen o BTcP; b) The he apeu ic
app oach o BTcP; and c) The clinical a ionale o admin-
is e ing en anyl ROOs o BTcP ea men .
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The e was a u he ex -based ques ion ha allowed
he expe s o p o ide a figu e o he p e alence o BTcP,
as in o med by hei own clinical p ac ice.
Finally, we asked 10 closed-ended ques ions abou any
pe cei ed di e ences be ween he di e en sys ems o
ou es o adminis e en anyl ROOs and he p e e ences
o pa icipan s.
Panelis s we e asked o indica e hei le el o ag eemen
wi h each s a emen using a nine-poin Like scale (one
being “s ongly disag ee,”nine being “s ongly ag ee”).
F ee ex space was also p o ided o encou age commen s.
Consensus defini ion and da a analysis
The median esponse (MED) and in e qua ile ange (IQR)
we e calcula ed o each s a emen . The le el o ag eemen
equi ed o consensus among he panel membe s was
decided p io o commencing he s udy.
Each s a emen ha eached a consensus wi h he espon-
den s was defined as a median consensus sco e (MED) o ≥7,
and ag eemen among panelis s as an in e qua ile ange
(IQR) o ≤3. Simila ly, a MED sco e o ≤3 was conside ed
o ep esen a consensus o ejec he s a emen .
An IQR o ≥4 equi ed a e iew o he c i e ia by he
SC ( ia discussion). The s a emen s in ques ion we e hen
ei he e ised and included in he second ques ionnai e, o
ejec ed based on addi ional commen s ecei ed om
panel membe s.
The ques ionnai e used in he second ound con ained
he p e ious median and IQR o he a ings ob ained in he
fi s ound o each e es ed s a emen , as well as some
commen s o cla i y he wo ding. Responden s we e asked
o e- a e each i em, using he in o ma ion om he p e-
ious ound as eedback, and o commen upon hei a -
ing. A e he second ound, he e ised MED and IQR
alues we e calcula ed.
Resul s
The pa icipan s we e made up o expe oncologis s om
14 o Spain’s 17 Au onomous Communi ies. In he fi s
ound, 69 ou o he 71 iden ified expe s (97.2%)
esponded (male, n=29; 42%). O he 69 ques ionnai es
ecei ed, 66 we e comple e, wo had wo missing i ems
and one had h ee missing i ems. All 69 esponden s who
ook pa in he fi s ound also esponded o he second
one wi h a 100% compliance a e (no missing i ems).
Response a es a e shown in Figu e 1. The s a emen s
p o ided o conside a ion and subsequen consensus
among pa icipan s a e shown in Table 1.
Defini ion and assessmen o BTcP
Rega ding he defini ion o BTcP, he expe s s ongly
ag eed upon i being an “Acu e exace ba ion o high-
in ensi y pain o sho du a ion and apid onse , su e ed
by a pa ien whose baseline pain is s abilized and con-
olled by opioids”(MED=9, IQR=1). In con as , he
s a emen defining BTcP as “mode a e” ailed o each an
accep able le el o ag eemen a e he second ound
(MED=7, IQR=5).
When a ing he cha ac e is ics and assessmen c i e ia
o BTcP diagnosis, expe s eached accep able consensus
sco es a e he second ound on he majo i y o c i e ia.
The s a emen “diagnosis o BTcP equi es mo e han ou
daily episodes” ailed o confi m a consensus, bu did
each qui e a high le el o ag eemen (IQR=2.5).
Quali a i e commen s made by he expe s eflec ed he
idea ha es ablishing a minimum numbe o episodes
could no help o define whe he a pa ien was su e ing
om BTcP, and ha an isola ed episode could be diag-
nosed and managed as BTcP. In e es ingly, in he fi s
ound, he s a emen “Valida ed pain assessmen ools
should be used in diagnosing BTcP” eached qui e a high
consensus sco e among he expe s (MED =7, IQR=3). In
he second ound, he i em was sligh ly changed o
“Medical judgmen in diagnosing BTcP p e ails o e ali-
da ed scales”, which imp o ed ag eemen le els (IQR=0).
The s a emen “A maximum o nine episodes pe day
demons a es a poo ea men o BTcP”was ejec ed
(MED=2, IQR=2). This was done on he g ounds ha
o e ou episodes a day should be conside ed a case o
poo baseline pain analgesia a he han BTcP. The e was
no consensus on he s a emen “Pa ien s a e eluc an o
epo pain due o ea o ea men ”(MED=5, IQR=4).
The i em ega ding he assessmen o QoL ailed o each a
consensus (MED=5, IQR=4) and he i em on he a ail-
abili y o ools o educa e pa ien s (MED=3, IQR=2)
eached a nega i e consensus, indica ing disag eemen .
Quali a i e commen s ag eed ha such s a emen s we e
jus ified, bu emphasized ha hey did no eflec daily
clinical p ac ice.
The apeu ic app oach in BTcP
A e he second ound, a high le el o consensus and an
accep able le el o ag eemen we e ob ained in ega d o
almos all o he s a emen s. Pa icula ly he ollowing
s a emen s: “po en , apid-onse opioids should be used o
ea BTcP”(MED=9, IQR=1); “ apid-onse en anyl is he
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ea men o choice o mos pa ien s su e ing om BTcP”
(MED=8, IQR=2); “ he s a egy o using he same opioid,
al hough in di e en o mula ions o baseline pain and
BTcP, is no necessa y”(MED=8, IQR=1); and “inciden al
BTcP ela ed o a p edic able igge ac o can be ea ed
wi h di e en en anyl o mula ions, aking he pa ien ’s
p e e ence in o accoun ”(MED=8, IQR=2).
Panelis s ejec ed he use o weak opioids (WHO s ep II
analgesics) as he ea men o choice o BTcP (MED=8,
IQR=2), as well as he use o immedia e- elease o al
opioids due o hei slow onse o ac ion (MED=7, IQR=3).
Clinical a ionale o adminis e ing apid-
onse en anyl opioids o BTcP
A e he fi s ound, i ems ela ing o cos -e ec i eness
we e emo ed om he ques ionnai e a e panelis s
exp essed hei un amilia i y wi h medica ion cos s. E en
so, hey eached a consensus, and a i ed a an adequa e
le el o ag eemen , in e ms o aking cos s in o accoun
when choosing a o mula ion o BTcP managemen
(MED=7, IQR=0). The e was widesp ead consensus ha
clinical p ac ice implies knowing he pha macokine ic p o-
file o he di e en en anyl o mula ions (MED=8,
IQR=2). Consequen ly, s a emen s sugges ing he bioequi-
alence o he apeu ic equi alence wi h ega d o p esc ib-
ing he di e en o mula ions we e ul ima ely ejec ed.
Pa ien s should play an inc easingly ac i e ole in he a-
peu ic choices (MED=9, IQR=1).
The su ey which esea ched he p e e ed ou e o
adminis a ion e ealed a ma ked bias owa ds sublingual
adminis a ion in e ms o pa ien and clinician p e e -
ences, usabili y in di e en ca e se ings, and ease o
adminis a ion o physically disabled pa ien s. The in a-
nasal adminis a i e ou e was conside ed o p o ide a
as e onse o ac ion, and o be mo e sui able o pa ien s
su e ing mucosi is. O al ansmucosal deli e y sco ed he
lowes ac oss all i ems. Table 2.
Las ly, he open-ended ques ion e ealed a high con-
sensus and o al ag eemen wi h ega d o he p e alence
o BTP in cance pa ien s (MED=7; IQR=0). The figu es,
Fundación eco-scien i ic commi ee
•Sc eening and ec ui men o medical oncology expe s
•De elopmen o he web-based ques ionnai e
71 medical oncologis in i ed o pa icipa e in he panel
Fi s phase: delphi su ey sen o 71 panelis s
69 esponde s (Response a e: 69/71, 97.2%)
Analysis o i s ound ou comes
Second phase: e a e each s a emen using summa y o esponses om he p e ious ound as
eedback and commen upon
Second phase: delphi su ey sen o 69 panelis s
69 esponde s (Response a e: 69/69; 100%)
Final esul s
Consensus
•Co ec use o BTcP de ini ion
•App op ia e ools o diagnose
•Fen anyl ROOs ea men o
choice o BTcP managemen
Ba ie s
•Mo e ime o isi s
•Pa ien ’s aining and educa ion
•Pa ien ’s in o ma ion ma e ial
Gaps
•Pa ien ’s quali y o li e
assessmen
•Technical knowledge o di e en
en anyl ROOs
•In o ma ion on cos
Key: BTcP: B eak h ough cance pain; ROOs: Rapid Onse Opioids
Figu e 1 Flowcha o pa icipan s in he s udy.
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Table 1 A ibu es conside ed o he diagnosis and managemen o BTcP by en anyl apid-onse opioids, and he consensus among pa icipan s
S a emen Mean Median IQR Ou lie s
(%)
Consensus
Inclusion/Exclusion
Acu e exace ba ion o HIGH-in ensi y pain, cha ac e ized by a sho du a ion and apid onse , su e ed by a pa ien whose baseline
pain is s abilized and con olled by opioids.
8.09 9 1 7.25 YES/incl.
Acu e exace ba ion o MODERATE pain, cha ac e ized by a sho du a ion and apid onse , su e ed by a pa ien whose baseline pain
is s abilized and con olled by opioids.
6.01 7 5 42.03 NO
Diagnosis o BTcP equi es mo e han ou daily episodes. 3.12 3 2.5 24.64 YES/excl.
Medical judgmen in diagnosing BTcP p e ails o e alida ed scales. 6.42 7 0 21.74 YES
Rou ine s anda dized pain scales such as VAS a e implemen ed o assess BTcP. 6.96 7 1 23.19 YES
The meaning ul pain in ensi y o BTcP diagnosis is >5/10 on a VAS scale. 7.09 7 1 10.14 YES
The sco e o con olled baseline pain is ≤3/10 on a VAS scale. 7.12 7 1 17.39 YES
Managemen o inciden BTcP (p edic able and ela ed o a p ecipi a ing ac i i y o e en such as walking) is easie han spon aneous BTcP. 7.42 8 2 18.84 YES
In clinical p ac ice, BTcP is shown o be highly p e alen in cance pa ien s. 8 8 2 7.25 YES
BTcP shows a high p e alence and la ge a iabili y. 7.41 8 2 17.39 YES
End-o -dose ailu e pain is no BTcP bu a he he esul o baseline medica ion unde dosing. 7.93 8 2 2.90 YES
End-o -dose ailu e pain can be easily mis aken o BTcP. 6.78 7 2 26.09 YES
A maximum o nine episodes pe day demons a es poo ea men o BTcP. 2.64 2 2 20.29 YES/excl.
Pa ien s a e eluc an o epo pain due o ea o ea men . 5.16 5 4 88.41 NO
Pa ien s do no complain abou BTcP unless hey a e exp essly asked abou i . 6.84 7 0.5 13.04 YES
S anda dized scales a e ou inely used o assess he pa ien ’s quali y o li e. 4.93 5 4 91.30 NO
Poo ly managed BTcP damages he pa ien ’s quali y o li e. 8.58 9 1 2.90 YES
Tools o educa e pa ien s a e usually a ailable, as a e guidelines o BTcP. 4.04 3 2 34.78 YES/excl
Un elie ed BTcP subs an ially aises heal hca e cos s due o inc eased ou pa ien and eme gency oom isi s. 8.04 8 2 2.90 YES
BTcP is a he e ogeneous condi ion as episodes a y bo h be ween pa ien s and wi hin he pa ien . 7.26 7 1 13.04 YES
Op imal he apy mus ake in o accoun di e en sub ypes o BTcP in indi idual pa ien s. 6.93 7 1 23.19 YES
The use o weak opioids (WHO s ep II analgesics) is no app op ia e o he managemen o BTcP. 7.41 8 2 17.39 YES
(Con inued)
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Table 1 (Con inued).
S a emen Mean Median IQR Ou lie s
(%)
Consensus
Inclusion/Exclusion
O al opioids, wi h hei slow onse o ac ion, a e inadequa e as hey may begin he analgesia a e pain has aba ed, he eby causing
ad e se e ec s.
6.74 7 3 27.54 YES
The s a egy o using he same opioid o he ea men o baseline pain and BTcP, bu in di e en o mula ions, is no necessa y 7.01 8 1 21.74 YES
The managemen o BTcP equi es po en opioids wi h apid onse o ac ion. 8.41 9 1 0 YES
The managemen o BTcP wi h apid-onse opioids is ese ed o hose pa ien s who a e NOT con olled wi h majo opioids o he
ea men o baseline cance pain.
2.9 3 1 15.94 YES/excl.
The managemen o BTcP equi es a ou e o adminis a ion ha minimizes he fi s -pass hepa ic me abolism (sublingual, ansmucosal,
in a enous, subcu aneous o spinal ou es) o p o ide high bioa ailabili y.
7.9 8 2 10.14 YES
The en anyl o mula ions ha e a as e onse o ac ion han immedia e- elease mo phine, which is clinically ele an o BTcP ea men . 8.3 9 1 1.45 YES
Fo mos cases o BTcP, apid-onse en anyl is he ea men o choice. 8.13 8 2 5.8 YES
The ideal analgesic o BTcP managemen should be a po en opioid, wi h apid onse , sho du a ion and easy adminis a ion. 8.57 9 1 0 YES
P edic able inciden BTcP can be managed h ough he adminis a ion o ei he as -ac ing en anyl o o al opioids. 5.32 7 4 49.28 NO
P edic able inciden BTcP can be managed by any o he apid-onse en anyl o mula ions acco ding o pa ien p e e ences. 7.93 8 2 7.25 YES
End o dose ailu e pain can be ea ed by:
- Inc easing he dose o he opioid 6.46 7 2.5 30.43 YES
- Dec easing he dosing in e al 6.77 7 1 18.84 YES
- Inc easing he dose and dec easing he dosing in e al 5.91 7 3 28.99 YES
In clinical p ac ice, i is essen ial o know he pha macokine ic p ofiles o he di e en en anyl o mula ions. 7.78 8 2 13.04 YES
All as -ac ing en anyl o mula ions (lozenges, sublingual able s, e e escen buccal able s o nasal sp ay) allow o easy dosing. 4.17 3 4 31.88 NO
Rapid onse o ac ion is he mos ele an ea u e when choosing a en anyl o mula ion o he managemen o BTcP. 7.23 7 2 18.84 YES
I makes no di e ence which as -ac ing en anyl o mula ion is used, as all o hem sha e he same ac i e ing edien : en anyl ci a e. 3.12 3 1 21.74 YES/excl.
The pha maceu ical o mula ion is no impo an in as -ac ing en anyl p oduc s. 2.90 3 1 21.74 YES/excl.
The ou e o adminis a ion is no clinically ele an o he managemen o BTcP. 2.61 3 2 10.14 YES/excl.
The pa ien ’s p e e ence should be conside ed when deciding on he ou e o adminis a ion. 8.25 9 1 1.45 YES
All as -ac ing en anyl o mula ions (lozenges, sublingual able s, e e escen buccal able s o nasal sp ay) ha e a simila ange o s eng hs. 5.3 5 4 72.46 NO
(Con inued)
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s a ed by he expe s, anged om 20–80%. In e es ingly,
one expe p o ided a figu e o 100% o bo h lung and
geni ou ina y cance s.
Discussion
The pu pose o his s udy was o each a consensus ha
would lay he ounda ions o he app op ia e managemen
o BTP in cance pa ien s. The fi s s ep o clinical diagnosis
is o discuss he pain. The e o e, he physician should make
su e o ask he pa ien explici ly abou pain fla es un il a
diagnosis o BTcP can be confi med.
27
The e was a di e -
ence o opinion among esponden s conce ning he defini ion
o BTcP. Mos expe s ag eed ha he qualifie “high”should
be included in he defini ion, bu ejec ed “mode a e;” his is
in line wi h he well-illus a ed con o e sy p esen in med-
ical li e a u e.
11,12,22
The e o e, his esul demons a es ha
BTcP implies a se e e pain, in e ms o in ensi y le els.
Acco ding o he expe s, diagnosing BTcP depends on
he p esence o well-con olled backg ound pain, which
means ha he de elopmen and p og ession o BTcP may
also ep esen p oblems ela ed o unde ea ed baseline
pain. The guidelines conside ha “adequa e con ol o
baseline pain”is an essen ial p e equisi e o begin specific
ea men o BTcP. Howe e , no clea defini ion exis s in
scien ific li e a u e.
15
In clinical p ac ice, analgesic he apy
o BTcP should be based on in eg a ion in o he back-
g ound pain’s he apeu ic s a egy. Howe e , i is no always
easy o dis inguish BTcP om a ia ions in he ou come
assessmen o baseline pain ( o ins ance, end-o -dose pain).
A ecen s udy ound ha whe e pa ien s had back-
g ound pain o ≤4/10 on a nume ical scale, he mean-
ing ul pain in ensi y a which hey asked o BTcP
medica ion was app oxima ely 7/10.
28
The expe s pa -
icipa ing in he p esen s udy ag eed ha ≤3/10 on a
VAS scale means “con olled,”implying e y mild
backg ound pain. Consequen ly, >5/10 means “mode -
a e”pain, and i is om his poin on he scale ha
BTcP should be assessed.
Rega ding he s a emen s on he use o opioids in
managing BTcP, oncologis s showed a g ea amoun o
knowledge. The SEOM (Spanish Socie y o Medical
Oncology) ecommenda ions
29
and ESMO
30
and EAPC
guidelines
8
s a e ha ROOs should be conside ed fi s -
line ea men o BTcP. In 2008, a su ey conduc ed in
Spain epo ed ha en anyl was la gely he opioid mos
commonly used o ea ing cance pain.
31
Indeed, clini-
cians showed app op ia e knowledge in he sa e and e ec-
i e use o apid-onse en anyl p epa a ions. Howe e ,
Table 1 (Con inued).
S a emen Mean Median IQR Ou lie s
(%)
Consensus
Inclusion/Exclusion
Specific a en ion should be paid o cos when choosing a o mula ion o as -ac ing en anyl o he managemen o BTcP. 6.71 7 0 18.84 YES
All o mula ions o as -ac ing en anyl a e o he same e ficacy. 3.58 3 0 21.74 YES/excl.
All o mula ions o as -ac ing en anyl o e he same sa e y p ofile. 3.38 3 0 17.39 YES/excl.
The ou es o adminis a ion o as -ac ing en anyl a e ou inely exchanged when ea ing BTcP. 3.91 3 2 30.43 YES/excl.
The di e en o mula ions o as -ac ing en anyl a e easily swi ched. 4.52 4 4 75.36 NO
The dose o as -ac ing en anyl should be i a ed. 6.2 7 0.5 24.64 YES
The e ec i e managemen o BTcP in ol es a combina ion o d ugs. 4.75 3 4 47.83 NO
Based on you clinical p ac ice, is he e a pe cen age o s able p e alence o BTcP in cance pa ien s? 6.58 7 0 21.74 YES
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hey sco ed poo ly when asked abou specific clinical
scena ios and hei scien ific and echnical knowledge
ega ding he di e en sys ems and ou es o adminis a-
ion. These gaps in hei knowledge concu wi h he find-
ings o p e ious s udies conduc ed in he USA and Asia,
indica ing ha oncologis s may no ully ealize hese
weaknesses in hei knowledge.
32,33
Expe s also highligh ed a no ewo hy conce n: limi ed
a en ion is paid o QoL, despi e i s impo ance in pa ien
well-being. In line wi h his, a ecen pan-Eu opean su ey
ound ha adul oncology pa ien s exp essed ha physi-
cians we e no in e es ed in hei QoL.
5
Simila ly, 52% o
pa ien s su eyed by he Ame ican Pain Founda ion
epo ed ha hey we e old BTcP was a no mal side e ec
o cance and/o i s ea men .
34
In his con ex , he p esen
s udy iden ified a need o dissemina e in o ma ion and
aise awa eness among medical oncologis s abou he bu -
den o BTcP on QoL. Wi h ha in mind, hey can ca y ou
hei ole co ec ly when dealing wi h his condi ion.
As o ba ie s o managing BTcP, expe s denied ha
pa ien s we e eluc an o epo pain. They did emphasize,
howe e , he absence o clea , app op ia e in o ma ion a ail-
able o pa ien s, as well as he limi ed amoun o ime hey had
in clinical p ac ice o discuss pain and educa e hem abou pain
managemen . These esul s a e simila o hose epo ed in
di e en su eys om all a ound he wo ld,
32,33,35
in which
ime limi a ions and pa ien aining we e iden ified as signifi-
can ba ie s o he e ec i e managemen o BTcP. Thus, i is
appa en ha he e is a need o he de elopmen o pa ien
in o ma ion esou ces ha p o ide clea and simple ins uc-
ions, as educa ion and pa ien compliance ha e been iden ified
as he mos impo an ac o s in app op ia ely managing pain.
2
While he e was a s ong consensus ha “Specific a en-
ion should be paid o cos when choosing a as -ac ing
en anyl o mula ion o BTcP managemen ”(MED=7;
IQR=0), i should be no ed ha ques ions abou cos we e
wi hd awn in he second ound due o quali a i e commen s
epo ing a lack o knowledge abou p ices. This finding
concu s wi h he lack o cos -e ec i eness analyses on
BTcP ea men s
36
and o al en anyl o mula ions, as ecen ly
s a ed by I alian clinicians.
37
Doc o s who p esc ibe hese
medica ions a e awa e o he subs an ial di e ence in cos
be ween en anyl o mula ions and immedia e- elease mo -
phine o oxycodone,
38
bu cos -e ec i eness analyses a e
needed in o de o help hem o selec he bes o mula ion.
37
In BTcP ea men , apid onse o ac ion and ease o
use a e uni e sal a iables in he p esc ip ion p ocess
ac oss all ca e se ings. Tha being said, we should no e
ha he cha ac e is ics o BTcP, he p e e ences o he
pa ien , and he he apeu ic se ing may influence hei
fi s he apeu ic choice. A possible change in he apeu ic
choice and he ou e o adminis a ion should also be aken
in o conside a ion.
Al hough compa ison s udies among di e en en anyl
o mula ions a e lacking, esul s om di e en s udies
showed ha he sublingual ou e is well accep ed by
pa ien s in e ms o ease and modali y o adminis a ion,
mucoadhesi i y, and hei o e all sa is ac ion,
39,40
which is
in line wi h he p e e ences epo ed in ou s udy. In anasal
adminis a ion seems p omising, bu in ol es he manda o y
use o specific deli e y de ices which a ec s usabili y.
41
The o al ansmucosal ou e o adminis a ion ecei ed a
lowe sco e o modali y o adminis a ion and he ime
aken o achie e pain elie ; u he mo e, his app oach
equi es expe ienced pa ien s.
16,17
In sho , oncologis s mus be awa e o he pa icula
ea u es o each medica ion, such as he di e en pha ma-
cokine ics, i a ion specifics, dosing in e als, and he
Table 2 Indica ions, con aindica ions and pha macokine ics o he di e en ou es o adminis a ion o apid onse en anyl
In anasal O al ansmucosal Sublingual
P e e ed by pa ien s √ √ √√√
Sui able o impai ed pa ien s √X√√√
Pa ien s wi h mucosi is √√√ √ √√
Pa ien s wi h diabe es √√√ X√√
P e e ed by clinicians √ √ √√√
Usabili y in any ca e se ing √√ √ √√√
Reduced dosing in e al √√√ √ √√
Fas e abso p ion √√√ √ √√
Easiness o i a ion √√ √ √√√
Wides ange o o ms and s eng hs X √ √√√
No es: √√√= (MED=≥8, IQR=≤1); √√= (MED=7; IQR=2–3) √= (MED=7; IQR=≥4); X= no consensus.
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echnical cha ac e is ics o i s accessibili y and deli e y, as
well as possible limi a ions in e e yday clinical p ac ice.
Acco ding o ou Delphi su ey (i ems wi h o wi hou
consensus), he e a e appa en knowledge gaps o be filled.
The e o e, ou esul s will need o be aken in o conside a-
ion when planning u u e ial analyses on en anyl o -
mula ions, so as o ex ac all he necessa y in o ma ion o
answe un esol ed ques ions abou i s use; new ials mus
be also de eloped.
Fu he mo e, he needs iden ified, ega ding he assessmen
and ea men o BTcP and he lack o awa eness su ounding
i s impac on pa ien s’QoL,couldbeused ode iseand
dissemina e use ul indica ions and ecommenda ions (which
could hen be included in aining p og ams o oncologis s).
The limi a ions o his s udy include i s decla ed ocus
on opioids, which has led o a lack o esul s in e ms o
he final consensus conce ning he in eg a ion o o he
ea men s a egies and me hods. Mo eo e , his su ey
was de ised o de elop and e alua e a consensus o spe-
cifically add ess se e e BTP ha esul s om cance o
cance ea men . I is he e o e possible ha i an al e -
na i e app oach we e used, di e en c i e ia would be
needed o ca y ou he s udy.
Finally, he consensus, based on expe opinion, ep e-
sen s a low le el o e idence wi h po en ial o bias, and
hus may no be en i ely accu a e. Al hough we selec ed ou
panel using an empi ical app oach based on clinical expe -
ise, we mus conside he possibili y o collec ing mo e
di e se esponses i we had a di e en selec ion o espon-
den s as pallia i e ca e physicians o anaes hesiologis s.
Conclusion
These findings ep esen a p agma ic app oach o he diag-
nosis and pha macological managemen o se e e BTcP.
The documen ed consensus can ac as a use ul ool o
analyze cu en clinical p ac ice. I also p o ides a ame-
wo k o p ope ly inqui ing abou RCTs and o e alua ing
he e ficiency and sa e y o he a ious ROOs o mula ions.
This consensus does no include specific ea men
ecommenda ions. This is due o he cu en ly es ablished
ule o adjus ing he dosage and ou e o adminis a ion
acco ding o he indi idual needs o each pa ien : indi i-
dualiza ion o BTcP opioid he apy is key o implemen ing
he mos e ec i e ea men .
Acknowledgmen s
The au ho s acknowledge all he medical oncologis s who
answe ed he su ey, as hei con ibu ion o his esea ch is
in aluable. We also acknowledge he membe s o he
Founda ion o Excellence and Quali y in Oncology o hei
suppo . This s udy was unded by Kyowa Ki in Fa macéu ica
S.L.U. h ough he Founda ion. Kyowa Ki in Fa macéu ica
was no in ol ed in he selec ion o pa icipan s no he con en
o his s udy.
Disclosu e
P o esso A Ca a o epo s pe sonal ees om Roche, Baye ,
Me ck, Se ie , and MSD, ou side he submi ed wo k.
P o esso E Díaz-Rubio epo s pe sonal ees om Me ck
Se ono, Amgen, Baye , Se ie , MSD, and Amgen, and g an s
om Amgen, Lilly, Roche, Me ck Se ono, and As aZeneca,
ou side he submi ed wo k. The au ho s epo no o he con-
flic s o in e es in his wo k.
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