Challenges in de e mining he global bu den o non-malignan cen al
ne ous sys em umo s: an analysis o in e na ional incidence and mo ali y
da a sou ces
Au ho s:
Ms. F ances Dean, MA.
Uni e si y o Cali o nia, San F ancisco: Compu a ional P ecision Heal h.
Uni e si y o Cali o nia, Be keley: Compu a ional P ecision Heal h.
Uni e si y o Washing on: Ins i u e o Heal h Me ics and E alua ion.
Popula ion Heal h Building/Hans Rosling Cen e , 3980 15 h A e. NE, Sea le, WA 98195 USA, UW
Campus Box #351615.
ances_dean@be keley.edu, 412-996-0279.
Ms. Hannah Hen ikson, MPH.
Bos on Uni e si y: School o Public Heal h.
715 Albany S , Bos on, MA, 02118 USA.
[email p o ec ed]
Ms. Rixing Xu.
Uni e si y o Washing on: Ins i u e o Heal h Me ics and E alua ion.
Popula ion Heal h Building/Hans Rosling Cen e , 3980 15 h A e. NE, Sea le, WA 98195 USA, UW
Campus Box #351615.
[email protected]
Ms. Hodo Fa ah.
2
Uni e si y o Washing on: Ins i u e o Heal h Me ics and E alua ion.
Popula ion Heal h Building/Hans Rosling Cen e , 3980 15 h A e. NE, Sea le, WA 98195 USA, UW
Campus Box #351615.
a [email protected]
Ms. Dan Lu.
Uni e si y o Washing on: Ins i u e o Heal h Me ics and E alua ion.
Popula ion Heal h Building/Hans Rosling Cen e , 3980 15 h A e. NE, Sea le, WA 98195 USA, UW
Campus Box #351615.
dlua [email protected]
M . James Ha ey.
Uni e si y o Washing on: Ins i u e o Heal h Me ics and E alua ion.
Popula ion Heal h Building/Hans Rosling Cen e , 3980 15 h A e. NE, Sea le, WA 98195 USA, UW
Campus Box #351615.
jamesdha @gmail.com
Ms. Weijia Fu, MS.
Uni e si y o Washing on: Ins i u e o Heal h Me ics and E alua ion.
Popula ion Heal h Building/Hans Rosling Cen e , 3980 15 h A e. NE, Sea le, WA 98195 USA, UW
Campus Box #351615.
[email protected]
D . Na alie P i che , DRPH.
Uni e si y o Washing on: Ins i u e o Heal h Me ics and E alua ion.
3
Popula ion Heal h Building/Hans Rosling Cen e , 3980 15 h A e. NE, Sea le, WA 98195 USA, UW
Campus Box #351615.
[email p o ec ed]
D . Nickhill Bhak a, MD.
S . Jude Child en’s Resea ch Hospi al: Depa men o Global Pedia ic Medicine.
262 Danny Thomas Pl, Memphis, TN 38105 USA.
Nickhill.Bhak [email protected] g
D . Daniel C. Mo ei a, MD.
S . Jude Child en’s Resea ch Hospi al: Depa men o Global Pedia ic Medicine.
262 Danny Thomas Pl, Memphis, TN 38105 USA.
Daniel.Mo ei [email protected] g
D . Ib ahim Qaddoumi, MD.
S . Jude Child en’s Resea ch Hospi al: Depa men o Global Pedia ic Medicine.
262 Danny Thomas Pl, Memphis, TN 38105 USA.
Ib ahim.Qaddoumi@s jude.o g
D . Fabio Gi a di, MD, PhD.
Cance Su i al G oup, Non-communicable Disease Epidemiology Depa men , London School o
Hygiene and T opical Medicine.
Keppel S ee , London, WC1E 7HT, UK.
Di ision o Medical Oncology 2, Vene o Ins i u e o Oncology IOV-IRCCS
Via Ga amela a 64, Padua, 35128, I aly.
4
abio.gi a di@lsh m.ac.uk
D . Theo Vos, MD.
Uni e si y o Washing on: Depa men o Heal h Me ics Sciences.
Uni e si y o Washing on: Ins i u e o Heal h Me ics and E alua ion.
Popula ion Heal h Building/Hans Rosling Cen e , 3980 15 h A e. NE, Sea le, WA 98195 USA, UW
Campus Box #351615.
[email p o ec ed]
D . Mohsen Nagha i, MD, PhD, MPH.
Uni e si y o Washing on: Depa men o Heal h Me ics Sciences.
Uni e si y o Washing on: Ins i u e o Heal h Me ics and E alua ion.
Popula ion Heal h Building/Hans Rosling Cen e , 3980 15 h A e. NE, Sea le, WA 98195 USA, UW
Campus Box #351615.
[email protected]
D . Jona han L. Finlay, MB ChB, FRCP (Lond.), FRCPCH.
Di ision o Hema ology, Oncology and Ma ow T ansplan a ion, Neu o-oncology P og am,
Na ionwide Child en’s Hospi al, and he Depa men s o Pedia ics and Radia ion Oncology
The Ohio S a e Uni e si y College o Medicine, Columbus, Ohio.
110 S Ma y A enue, Sui e 2-291, Nipomo, CA 93444
neu [email protected]
D . Lisa M. Fo ce, MD.
Uni e si y o Washing on: Depa men o Pedia ics, Di ision o Pedia ic Hema ology-Oncology.
5
Uni e si y o Washing on: Depa men o Heal h Me ics Sciences.
Uni e si y o Washing on: Ins i u e o Heal h Me ics and E alua ion.
Popula ion Heal h Building/Hans Rosling Cen e , 3980 15 h A e. NE, Sea le, WA 98195 USA, UW
Campus Box #351615.
[email p o ec ed]u
6
Abs ac
Backg ound
Non-malignan umo s o he CNS con ibu e subs an ially o he mo bidi y and mo ali y om CNS umo s. I is
c i ical o unde s and he epidemiology o non-malignan CNS umo s sepa a ely om CNS malignancies o in o m
esou ce alloca ion and policy since ea men and p ognosis can di e . High quali y in e na ional da a on non-
malignan CNS umo bu den a e needed o accomplish his goal.
Me hods
We assessed cance egis y and i al egis a ion da a a ailable o he Global Bu den o Disease s udy by i s
inclusion o non-malignan CNS umo s, epo ing on he a ailabili y o da a o e ime and by Wo ld Bank income
g oup. We analyzed p elimina y age-s anda dized incidence a es (ASIRs), age-s anda dized mo ali y a es
(ASMRs), and p opo ions o CNS umo s by beha io o adul s, child en, and all ages.
Resul s
Non-malignan CNS umo s we e epo ed sepa a ely in 17·2% (N=66) o egis y epo s and in agg ega e wi h
malignan CNS umo s in 18·0% (N=69) o epo s. Only se en low- and middle-income coun ies (LMICs) had
da a epo ing CNS umo s sepa a ely by beha io . Ac oss all ages combined, he median ASIR o non-malignan
CNS umo da a was 0·31 (in e qua ile ange: 0·15-0·50) and ASMR was 0·24 (0·10-0·44) pe 100,000 in LMICs
compa ed o median ASIR o 3·62 (2·62-4·97) and ASMR o 0·32 (0·16-0·65) in high-income coun ies (HICs). A
la ge p opo ion o inciden CNS umo s we e epo ed as non-malignan in HIC da a han LMIC da a (p<0.0001).
Conclusions
Ou s udy alludes o cu en challenges in unde s anding global non-malignan CNS umo bu den and a need o
inc eased in e na ional da a collec ion. Fu he esea ch is needed o comp ehensi ely in es iga e oppo uni ies o
u u e da a inclusion.
Keywo ds
non-malignan CNS umo s, popula ion-based cance egis ies, i al egis a ion sys ems, incidence, mo ali y
Key poin s
7
• Global epo ing o non-malignan CNS umo s by popula ion-based cance egis ies and i al egis a ion
sys ems shows a ia ion and challenges.
• Less da a and lowe a es om low- and middle-income coun ies sugges s a need o u he esea ch.
Impo ance o he S udy
Few p io s udies o in e na ional CNS umo bu den ha e ocused on non-malignan umo s. Mos p e ious
esea ch has ocused on incidence, ypically wi hin a single na ion. Complica ing esea ch in his space, i has been
sugges ed by p io s udies ha hese umo s a e unde epo ed in many se ings. To ou knowledge, his s udy is he
i s o desc ibe epo ing pa e ns and da a a ailabili y o non-malignan CNS umo s by cance egis ies
in e na ionally o e ime and o p esen da a on non-malignan CNS umo mo ali y. We obse ed g ea e epo ing
and highe incidence and mo ali y a es in da a om high-income coun ies, o all ages combined, as well as o
child en and adul s sepa a ely. Ou da a, oge he wi h p e ious s udies, sugges ha ewe non-malignan CNS
umo s a e epo ed in low- and middle- income coun ies. The p ecise d i e s behind hese di e ences a e unclea
and mo e esea ch is needed o comp ehensi ely desc ibe po en ial biologic e sus heal h sys ems o o he
con ibu o s.
8
In oduc ion
Non-malignan umo s o he cen al ne ous sys em (CNS) cause subs an ial mo bidi y and p ema u e mo ali y
despi e o en being e e ed o as “benign” umo s.1–4 The e o e, unde s anding he epidemiology o non-malignan
CNS umo s is impo an o comp ehensi ely es ima e global cance bu den. As ea men may include
neu osu gical esec ion, chemo he apy, and adio he apy o CNS umo s o any beha io , in o ma ion on ends in
non-malignan CNS umo s a e c i ical clinically, o esou ce alloca ion decisions, and o policy de elopmen .5–7
The WHO Global Ini ia i e o Childhood Cance ecen ly iden i ied low-g ade gliomas as one o six key indica o
cance s o measu ing p og ess in childhood cance su i al, u he unde sco ing he need o eliable es ima es o
he global and local bu den o non-malignan CNS umo s.8
Global age, sex, and geog aphic pa e ns o indi iduals wi h non-malignan CNS umo s a e hough o di e om
hose o malignan CNS umo s.2,3 Non-malignan meningiomas occu in highe a es in emales han in males in
adul s, and his di e ence by sex a ies ac oss coun ies.3,4,9–12 Non-malignan CNS umo s compose a a ying
p opo ion o CNS umo s by age wi h high-income coun ies (HICs), such as he Uni ed S a es, desc ibing ha
app oxima ely one- hi d o childhood CNS umo s a e non-malignan umo s compa ed o o e wo- hi ds o CNS
umo s being non-malignan in adul s.3 Less is known abou he epidemiologic pa e ns o childhood non-malignan
CNS umo s in many coun ies a ound he wo ld, pa icula ly in coun ies wi h limi ed esou ces.1,2,13,14 The
p opo ion o b ain umo s classi ied as low-g ade as ocy omas in child en a ied om less han 10% o mo e han
30% ac oss 60 coun ies in a ecen s udy om CONCORD-3.2 The p opo ion o pedia ic CNS umo s classi ied as
non-malignan also a ied ac oss Eu opean coun ies in a s udy om EUROCARE-5.15 Toge he hese p io s udies
sugges a need o mo e g anula and obus da a on non-malignan CNS umo s o disce n ue epidemiology.
Neglec ing non-malignan CNS umo es ima es would be expec ed o signi ican ly unde es ima e he bu den and
impac o CNS umo s wo ldwide. To accu a ely es ima e he epidemiologic pa e ns o non-malignan CNS umo s,
high quali y in e na ional da a on hei bu den a e necessa y. While malignan CNS umo s a e egis e ed by mos
popula ion-based cance egis ies, he egis a ion o non-malignan CNS umo s a ies g ea ly.2,16 The Global
Bu den o Disease (GBD) s udy i e a i ely es ima es he bu den o o e 300 diseases and inju ies, including CNS
cance s, wo ldwide, bu non-malignan CNS umo bu den is no es ima ed sepa a ely.17 Da a sou ces o he GBD
s udy include popula ion-based cance egis y epo s and da a om i al egis a ion sys ems. In his manusc ip ,
9
we pe o m a p elimina y analysis o he in e na ional malignan and non-malignan CNS umo incidence and
mo ali y da a a ailable o he GBD s udy, analyzing a ia ion in popula ion-based cance egis y and i al
egis a ion sys em epo ing pa e ns and unp ocessed non-malignan CNS umo incidence and mo ali y da a.
Ma e ials and Me hods
Ou s udy de ined non-malignan CNS umo s as g ade I o II in he WHO g ading scheme and included umo s
classi ied as o low-g ade o unce ain beha io .18 We use he e m non-malignan a he han ‘benign’ o ‘low-
g ade’ due o ou inclusion o umo s o unce ain beha io , as well as o acknowledge ha he impac o hese
umo s is no benign. Disease codes conside ed o ep esen non-malignan umo s o he CNS included ICD-10
codes D32-D33, D35.2-D35.4,19 ICD-9 code 225,20 and ICD-O-3 opog aphy codes C70-72, and C75.1-C75.3 when
combined wi h beha io code 0 o bo h incidence and mo ali y.21 ICD-10 codes D42-D43, D44.3-D44.5, D49.6,
ICD-9 codes 237, 239.6, and he abo e ICD-O-3 opog aphy codes combined wi h beha io code 1 we e conside ed
CNS umo s o unce ain beha io and included in his analysis as non-malignan umo s o bo h incidence and
mo ali y. In e na ional Classi ica ion o Childhood Cance , hi d edi ion (ICCC-3) codes IIIa- and Xa we e
conside ed o include incidence o all CNS umo beha io s unless s a ed o he wise.22
Cance egis y da a e iew
We pe o med a e iew o he cance egis y (CR) sou ces a ailable o he GBD s udy o es ima e cance bu den.
The GBD s udy has his o ically modeled malignan CNS cance s by using da a on all CNS umo s epo ed unde an
in asi e disease code o label by any a ailable i al egis a ion (VR) and popula ion-based CR da a sou ce om he
yea s 1980 h ough he cu en GBD s udy yea . CR sou ces conside ed sui able o use in he GBD s udy mus
epo comp ehensi ely on commonly epo ed cance s and ideally sepa a e da a by sex, in a leas i e-yea age
g oups, and in singula yea bins, al hough excep ions a e made such as o childhood CRs, which o en p esen da a
agg ega ed o e se e al yea s. Da a a ailabili y esul s in his analysis a e p esen ed by da ase . A single da ase in
he GBD s udy may con ain incidence om mo e han one CR and may ep esen se e al yea s. In some cases,
da ase s ep esen umo s in a single coun y. In o he cases, he GBD s udy inco po a es da a om la ge epo ing
publica ions, such as he In e na ional Incidence o Childhood Cance (IICC) se ies o Cance Incidence in Fi e
Con inen s (CI5) se ies, in which a GBD ‘da ase ’ may ep esen da a om many CRs a ound he wo ld. Da a
conside ed unusable by he GBD s udy we e conside ed unusable o his p elimina y analysis as well. In addi ion,
16
ound a g ea e p opo ion o non-malignan umo cases in addi ion o highe ASIRs o CNS umo s o e all in he
highe income se ing (Swi ze land).25 Ou esul s also co obo a e p io indings ac oss mul iple coun ies and
income se ings ha emales may ha e highe p opo ions o non-malignan CNS umo s when assessed ac oss all
ages combined, which has p e iously been a ibu ed o a g ea e incidence o meningiomas.3,4,11,12,26 These p io
analyses laid c i ical g oundwo k in assessing di e ences in CNS umo incidence by beha io in e na ionally, wi h
ou s udy adding a p elimina y assessmen o incidence da a a ailabili y and limi a ions ac oss Wo ld Bank income
g oupings o e ime as well as an in o mal analysis o mo ali y da a.
Toge he , his li e a u e sugges s possible di e ences in epidemiological ends o non-malignan CNS umo s wi h
highe ASIRs, ASMRs, and p opo ions o non-malignan CNS umo s occu ing in HICs, as simila ends ha e
been obse ed by p e ious s udies.9,27,28 These da a should be in e p e ed hough ully and con inued in es iga ion o
unde s and he oo di e ences in ends is necessa y due o he po en ial o incomple e cap u e o bo h non-
malignan and malignan CNS umo s in some disease su eillance sys ems. The po en ial o unde epo ing may be
g ea e in LMICs gi en da a spa si y, lowe epo ed ASIRs o CNS umo s o all beha io s, and lowe epo ed
p opo ions o non-malignan CNS umo cases and dea hs.3,4,11,13,29 I is also possible ha gene ic ac o s could
con ibu e o a ia ions in bu den o CNS umo s in e na ionally.9,28,30
The po en ial con ibu ion o low case asce ainmen o lowe ASIRs and ASMRs alludes o possible bene i o
u u e s a is ical modeling o accoun o unde es ima ion. Longe e m, add essing he easons o less da a
a ailabili y and po en ially lowe non-malignan CNS umo case asce ainmen in LMICs will be impo an . These
easons a e likely mul i ace ed; indi iduals may no seek medical ca e in lowe esou ce se ings, access o ca e may
be subop imal, and e icien e e al s eams o special y ca e may no exis . The diagnosis o non-malignan CNS
umo s may also be challenging due o lack o clinical p o ide s, diagnos ic imaging, o quali y pa hology e iew,
leading o po en ial o misdiagnosis as a malignan CNS umo o o he in ac anial p ocess.31 E en i diagnosed,
epo ing o non-malignan CNS umo s by CRs has ba ie s. O e he pas se e al decades, he e ha e been many
changes in CNS umo classi ica ion and epo ing p ac ices ac oss and wi hin coun ies, and CRs o en ope a e wi h
limi ed unding and s a ing.28,32,33 As has been p e iously aised,2 he cu en ICCC disease classi ica ion scheme
makes i challenging o dis inguish CNS umo s o di e en beha io s, and he e is wo k ongoing o imp o e he
epo ing o CNS umo s in child en.34 In e na ional epo ing is also hinde ed by non-malignan CNS umo s no
longe being included in he Cance Incidence in Fi e Con inen s se ies ollowing e sion VI in 1997.33
17
Fu he esea ch and a ge ed implemen a ion s a egies, in close collabo a ion wi h CRs a ound he wo ld, a e
needed o comp ehensi ely in es iga e he ba ie s o epo ing non-malignan CNS umo bu den and po en ial
enable s o hei u u e inclusion in epo s. Ou s udy alludes o he need o cla i y in CR p ac ices and epo ing
o non-malignan CNS umo s, which would bene i knowledge o global CNS umo bu den. When umo s a e no
egis e ed, ei he due o sys ema ic o ope a ional ba ie s, he disease ca ego y emains in isible om a public
heal h pe spec i e. Thus, hese da a highligh ha s anda d epo ing ac oss geog aphic bounda ies a e c i ical o
ul ima ely imp o e diagnos ics, ea men access and quali y o ca e o indi iduals wi h CNS umo s wo ldwide.
P e ious esea ch showed ha he implemen a ion o Public Law 107-260 equi ing benign CNS umo egis a ion
in he Uni ed S a es con ibu ed o an inc ease in non-malignan CNS umo incidence epo ed, which s abilized a
ew yea s ollowing he s a u e.35 Howe e , i is unlikely ha egis y manda es alone would be su icien o
comple ely cap u e non-malignan CNS umo bu den, and adequa e CR suppo in addi ion o imp o emen s in
access o ca e and diagnosis ac oss geog aphies will be c i ical o an accu a e unde s anding o , and imp o ed
ou comes o , CNS umo bu den globally.
This s udy is an impo an analysis o in e na ional non-malignan CNS umo da a a ailabili y. We con ibu e a
comp ehensi e analysis o CR epo ing o non-malignan CNS umo da a, highligh ing he need o s anda dized
inclusion o non-malignan CNS umo s and mo e da a om low esou ce se ings. We also epo p elimina y
analyses o non-malignan CNS umo incidence and mo ali y da a, con ibu ing o li e a u e ha can in o m public
heal h policy. S ill, ou s udy has se e al limi a ions. Da a sou ces a ailable o use in he GBD s udy as o Augus
2020 we e analyzed, and gi en he ime equi ed o egis ies o epo da a, da a we e a ailable h ough 2018 o
e alua ion. Mo eo e , he e a e da a on non-malignan CNS umo s ha we e no acqui ed by he GBD p io o his
da e and a e hus excluded om his s udy. VR and CR da a sou ces we e analyzed in as aw o o ms as possible
gi en ha he p ima y aim o his analysis was o assess da a a ailabili y and challenges wi h da a a ailable o his
cance ype in e na ionally. Thus, da a we e no p ocessed o op imal ha moniza ion and adjus men s as would
ypically be he case in he GBD s udy, and analysis would be an icipa ed o change as p ocessing s eps a e applied
o he cu en da a and as new da a sou ces a e added. Fu he , da a use equi emen s limi ed he use o some da a a
op imal g anula i y, and some egis ies may collec non-malignan CNS umo da a ha we e no a ailable o his
analysis. The con ibu ion o unspeci ied umo s, which we e included in ou analyses as non-malignan , may also
impac ou esul s. Finally, no all coun ies ha e CR o VR sys ems, which limi s he gene alizabili y o ou
18
explo a o y summa ies o incidence and mo ali y esul s and u he unde sco es he need o con inued
de elopmen and suppo o sus ainable cance su eillance sys ems capable o cap u ing and epo ing non-
malignan CNS umo s.
Ou s udy illus a es a need o inc eased in e na ional da a on non-malignan CNS umo bu den, pa icula ly in
LMICs, as well as a need o collabo a i e de elopmen o s anda dized epo ing ecommenda ions, e e al
pa hways, and policies ha allow o cha ac e iza ion o non-malignan CNS umo bu den sepa a ely om
malignan o imp o e ou unde s anding o o e all CNS umo bu den. Ou in o mal explo a o y analysis o he
a ailable da a sugges s inc easing ASIRs, ASMRs, and p opo ions o o al CNS umo s ha a e non-malignan wi h
inc easing Wo ld Bank income s a us and can p o ide a s a ing poin o u he esea ch in o he bes s a egies o
imp o emen o da a cap u e and epo ing p ac ices.
Da a A ailabili y
Da a used in his s udy will be made a ailable upon eques unless p ohibi ed by da a use ag eemen s.
Funding
Bill and Melinda Ga es Founda ion, S . Jude Child en’s Resea ch Hospi al Comp ehensi e Cance Cen e
[P30CA021765]; Ame ican Lebanese Sy ian Associa ed Cha i ies (ALSAC)
Acknowledgemen s
We a e g a e ul o he cance egis ies and i al egis a ion sys ems ha make da a a ailable o analysis and o all
who a e wo king o imp o e he li es o indi iduals wi h CNS umo s a ound he wo ld.
Con lic o In e es
All au ho s decla e no con lic o in e es .
19
Au ho Con ibu ions
Concep ion o he wo k: F ances Dean, Nickhill Bhak a, Lisa M. Fo ce. Da a analysis: F ances Dean, Hannah
Hen ikson, Rixing Xu, Hodo Fa ah, Dan Lu, James Ha ey, Weijia Fu, Na alie P i che . Da a acquisi ion and
in e p e a ion: F ances Dean, Nickhill Bhak a, Daniel C. Mo ei a, Ib ahim Qaddoumi, Fabio Gi a di, Mohsen
Nagha i, Theo Vos, Jona han L. Finlay, Lisa M. Fo ce. D a o he manusc ip : F ances Dean, Lisa M. Fo ce.
C i ical e ision o he manusc ip : all au ho s. Final app o al o he manusc ip : all au ho s. Ag eemen o be
accoun able o all aspec s o he wo k: all au ho s.
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23
Figu es
Ca ego y
Desc ip ion
% o Incidence Da a
(N=383 Da ase s)
% o Mo ali y Da a
(N=132 Da ase s)
I
Non-malignan CNS umo s epo ed
sepa a ely om malignan
17.2%
(N = 66)
27.3%
(N = 36)
II
All beha io s o CNS umo s epo ed
in agg ega e
18.0%
(N = 69)
11.4%
(N = 15)
III
Malignan CNS umo s only epo ed
and speci ies o exclude non-
malignan
22.5%
(N = 86)
11.4%
(N = 15)
IV
Malignan CNS umo s epo ed and
speci ies o include in si u o
unce ain
3.1%
(N = 12)
3.0%
(N = 4)
V
Malignan CNS umo s only epo ed
wi hou speci ying o exclude non-
malignan
39.0%
(N = 150)
47.0%
(N = 62)
Table 1. Global Bu den o Disease (GBD) s udy cance egis y incidence and mo ali y da a a ailabili y,
ca ego ized by how CNS umo da a we e epo ed.
24
Figu e 1. Coun ies wi h a leas one popula ion-based cance egis y epo o non-malignan CNS umo s
(a) p io o 2000 and (b) om 2000 onwa d in he GBD s udy. Coun y colo s a e based on he exis ence o any
na ional o subna ional cance egis y da a on CNS umo s om 1980 o 2018 in he GBD da abase as o Augus 8,
2020. I a coun y had any da a in ha ime ame om ca ego y I, i was colo ed da k blue. I a coun y did no ha e
any da a in ca ego y I bu had da a in ca ego y II, i was colo ed ligh blue unless he da a was pedia ic only o
coded in ICCC and did no speci y inclusion o non-malignan CNS umo s in which case i was colo ed yellow o
o ange, espec i ely. Coun ies wi h da a in ca ego ies III, IV, V o no usable GBD da a a e colo ed ed o indica e
he absense o non-malignan CNS umo da a a ailable o he GBD s udy. Da a on non-malignan CNS umo s no
ye used o he GBD s udy may exis bu a e no ep esen ed in his igu e. Abb e ia ions: ICCC=In e na ional
Classi ica ion o Childhood Cance , GBD=Global Bu den o Disease S udy.
25
Figu e 2. Median sex-speci ic ASIRs o CNS umo s om unp ocessed cance egis y da a sou ces by
beha io and age g oup ac oss Wo ld Bank income g ouping om 1980-2018. Black ba s ep esen
in e qua ile ange. Abb e ia ions: ASIRs=age-s anda dized incidence a es, HICs=High-income coun ies,
LMICs=Low- and middle-income coun ies.
5
Appendix Figu e 4. Age-s anda dized cance egis y unp ocessed incidence da a a es ac oss all ages and
bo h sexes combined agains SDI by da ase ca ego iza ion. Da a om Alge ia and Hunga y we e omi ed due o
a lack o eliable popula ion es ima es om he egis y o by he GBD s udy o he egion o geog aphic co e age.
Da a om Japan was omi ed because i was p esen ed in an all-ages agg ega ed o m. Da a om he ollowing
coun ies we e omi ed due o da a use ag eemen s: Uni ed S a es, China, Bela us, and Tu key. Abb e ia ions:
ASIRs=age-s anda dized incidence a es, CNS=Cen al Ne ous Sys em, SDI=Socio-demog aphic Index.
Appendix Figu e 5. Pedia ic CNS umo ASIRs by beha io .
Appendix Figu e 5. Combined sex, pedia ic (0-14 yea s) ASIRs o CNS umo s om unp ocessed cance
egis y da a sou ces by beha io ac oss SDI. Each poin ep esen s an annual ASIR om a cance egis y sou ce
be ween 1980 and 2018. Da a om Alge ia and Hunga y we e omi ed due o a lack o eliable popula ion es ima es
om he egis y o by he GBD s udy o he egion o geog aphic co e age. Da a om Japan was omi ed because
i was p esen ed in an all-ages agg ega ed o m. Da a om he ollowing coun ies we e omi ed due o da a use
ag eemen s: Uni ed S a es, China, Bela us, Tu key. Abb e ia ions: ASIRs=age-s anda dized incidence a es,
CNS=Cen al Ne ous Sys em, SDI=Socio-demog aphic Index.
6
Appendix Figu e 6. All ages CNS umo ASMRs by beha io .
Appendix Figu e 6. Combined sex, all ages ASMRs o CNS umo s om unp ocessed cance egis y and i al
egis a ion da a sou ces by beha io ac oss SDI. Each poin ep esen s an annual ASMR om a da a sou ce o a
loca ion (na ional o sub-na ional) be ween 1980 and 2018. Abb e ia ions: ASMRs=age-s anda dized mo ali y
a es, CNS=Cen al Ne ous Sys em, SDI=Socio-demog aphic Index.
Appendix Figu e 7. Pedia ic CNS umo ASMRs by beha io .
Appendix Figu e 7. Combined sex, pedia ic (0-14 yea s) ASMRs o CNS umo s om unp ocessed cance
egis y and i al egis a ion da a sou ces by beha io ac oss SDI. Each poin ep esen s an annual ASMR
om a da a sou ce o a loca ion (na ional o sub-na ional) be ween 1980 and 2018. Abb e ia ions: ASMRs=age-
s anda dized mo ali y a es, CNS=Cen al Ne ous Sys em, SDI=Socio-demog aphic Index.
7
Appendix Figu e 8. P opo ions o pedia ic CNS umo cases by beha io .
Appendix Figu e 8. P opo ion o CNS umo cases in child en (0-14 yea s) ha a e malignan and non-
malignan in unp ocessed cance egis y da a, p esen ed by sex and Wo ld Bank income s a us.
Abb e ia ions: CNS=Cen al Ne ous Sys em, HIC= High income coun ies, LMIC=Low- and middle-income
coun ies.
Appendix Figu e 9. P opo ions o pedia ic CNS umo dea hs by beha io .
Appendix Figu e 9. P opo ion o CNS umo dea hs in child en (0-14 yea s) ha a e malignan and non-
malignan in unp ocessed cance egis y and i al egis a ion da a, p esen ed by sex and Wo ld Bank
income s a us. Abb e ia ions: CNS=Cen al Ne ous Sys em, HIC= High income coun ies, LMIC=Low- and
middle-income coun ies.
8
Appendix Figu e 10a. Coun ies wi h i al egis a ion da a o non-malignan CNS umo s p io o 2000.
Appendix Figu e 10a. Coun ies wi h a leas one i al egis a ion dea h epo ed o non-malignan CNS
umo s p io o 2000. Coun ies a e colo ed based on he a ailabili y o any nonze o da a on non-malignan CNS
umo s om 1980 o 1999. Abb e ia ions: CNS=Cen al Ne ous Sys em.
Appendix Figu e 10b. Coun ies wi h i al egis a ion da a o non-malignan CNS umo s om 2000 o
2018.
Appendix Figu e 10b. Coun ies wi h a leas one i al egis a ion dea h epo ed o non-malignan CNS
umo s om 2000 o 2018. Coun ies a e colo ed based on he a ailabili y o any nonze o da a on non-malignan
CNS umo s om 2000 o 2018. Abb e ia ions: CNS=Cen al Ne ous Sys em.
Addi ional in o ma ion on da a ep esen ed in igu es.
No i al egis a ion sys em da a wi h non-
malignan CNS umo s a ailable
No i al egis a ion sys em da a wi h non-
malignan CNS umo s a ailable
Vi al egis a ion sys em da a wi h non-
malignan CNS umo s
Vi al egis a ion sys em da a wi h non-
malignan CNS umo s
9
Main ex Figu e 3.
Da a om Alge ia and Hunga y we e omi ed due o a lack o eliable popula ion es ima es o he egion o
geog aphic co e age. Da a om Japan was omi ed because i was p esen ed in an all-ages agg ega ed o m. Da a
om he ollowing coun ies we e omi ed due o da a use ag eemen s: Uni ed S a es, China, Bela us, and Tu key.
Main ex Figu e 5a.
High income coun ies included in analysis: Canada, C oa ia, Hunga y, Slo enia, Li huania, Japan, Is ael, I aly,
Uni ed Kingdom, I eland, Es onia, and F ance. Low- and middle-income coun ies included: A gen ina, Alge ia, and
E hiopia.
Appendix Figu e 8.
Da a om Japan was omi ed because i was p esen ed in an all-ages agg ega ed o m. Da a om he ollowing
coun ies we e omi ed due o da a use ag eemen s: Uni ed S a es, China, Bela us, Tu key. High-income coun ies
included: C oa ia, Hunga y, Slo enia, Li huania, Japan, Is ael, I aly, Uni ed Kingdom, Mal a, and Es onia. Uppe
middle income: A gen ina. Lowe middle income: Alge ia. Low income: E hiopia.
Main ex Figu e 5b and Appendix Figu e 9.
Da a om he ollowing coun ies we e included. High-income coun ies: Uni ed A ab Emi a es, An igua and
Ba buda, Aus alia, Aus ia, Belgium, Bah ain, Bahamas, Be muda, Ba bados, B unei Da ussalam, Canada,
Swi ze land, Chile, Cyp us, Czechia, Ge many, Denma k, Spain, Es onia, Finland, F ance, Uni ed Kingdom,
G eece, G eenland, Guam, C oa ia, Hunga y, I eland, Iceland, Is ael, I aly, Japan, Sain Ki s and Ne is, Republic o
Ko ea, Kuwai , Li huania, Luxembou g, La ia, Monaco, Mal a, No he n Ma iana Islands, Ne he lands, No way,
New Zealand, Oman, Poland, Pue o Rico, Po ugal, Qa a , Saudi A abia, Slo akia, Slo enia, Sweden, T inidad and
Tobago, Taiwan (P o ince o China), U uguay, Uni ed S a es o Ame ica, and Uni ed S a es Vi gin Islands. Uppe
middle-income coun ies: Albania, A gen ina, A menia, Ame ican Samoa, Aze baijan, Bulga ia, Bosnia and
He zego ina, Bela us, China, Cos a Rica, Cuba, Dominica, Dominican Republic, Ecuado , Geo gia, G enada,
Gua emala, Guyana, I aq, Jo dan, Kazakhs an, Lebanon, Libya, Sain Lucia, Republic o Moldo a, Maldi es,
Mexico, No h Macedonia, Mau i ius, Malaysia, Panama, Romania, Russian Fede a ion, Se bia, Su iname, Thailand,
Tü kiye , Sain Vincen and he G enadines, Sou h A ica. Lowe middle-income coun ies: Belize, Boli ia
(Plu ina ional S a e o ), Cabo Ve de, Egyp , Ghana, Hondu as, Hai i, India, I an (Islamic Republic o ), Ky gyzs an,
Solomon Islands, El Sal ado , Tunisia, Uk aine, Uzbekis an.
