Cheklist Malignancy Estella

8/17/2019 Cheklist Malignancy Estella

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Guidelines Pediatric Oncology Center, for the Estella Children’s CancerClinics

Translated and paraphrased from the VUmc Pediatric Oncology-Hematology epartment

By Prof Anjo JP Veerman, October 2014

!"T#O UCT!O"

The care for patients with cancer is comple ! "any professionals play a role! Theresi#ents are the $in%pin of care on the war#! These %&i#elines are for allin'ol'e#, b&t especially for the #octors in the (rst line of treatment of chil#hoo#cancer) the resi#ents! B&t of co&rse these %&i#elines ha'e to be s&pporte# an#acti'ate# an# intro#&ce# to all new resi#ents on the war#! *itho&t learnin% theser&les by heart no resi#ent sho&l# be allowe# on the war#!

iagnostic Phase

*hen a chil# is a#mitte# with a +pres&me# #ia%nosis of mali%nancy, of co&rsethe whole family will be f&ll of sorrow! *hat will happen- .or many peoplemali%nancy is a #eath warrant! /o it is important for the #octors an# n&rses toha'e intense an# repeate# inter'iews with the parents an# sometimes%ran#parents or other family members ! .irst inter'iews may be &ite short, toinform the family abo&t the imme#iate proce#&res! ater on, the ne t #ay forinstance, more elaborate information may ta$e half an ho&r, an# in the ne t few#ays an inter'iew of maybe 10 min&tes is eno&%h! "&ch #epen#s on the wishes

of the family in this respect! B&t #aily contact will help to %i'e the family tr&st inthe pe#iatric oncolo%y team! planation will be re &ire# abo&t the #ia%nosticmeas&res to be ta$en, an# the propose# treatment, as well as the chances ofc&re! 3f a #ia%nosis of mali%nancy is ma#e, sta%in% is important for the correcttreatment protocol an# for the pro%nosis! The chec$list new patients will help toma$e a #ia%nostic plan!

Pre-Treatment Phase

3f the e act #ia%nosis is certain an# the sta%e of the #isease is ascertaine#, thetreatment plan can be set &p! .or soli# t&mors, the plan has to be #isc&sse# inthe T&mor Boar#, with the rele'ant other specialists! e t to the pe#iatriconcolo%ist an# responsible resi#ent, that will always be the ra#iolo%ist, mostoften the pe#iatric s&r%eon, or ophthalmolo%ist an# a pe#iatric oncolo%y n&rse aswell as social wor$er an# psycholo%ist sho&l# be present!

The family will be informe# abo&t the treatment plan! This will entail #isc&ssin%the #ia%nosis, the treatment, the pro%nosis! Also si#e e5ects #&rin% treatmentan# a short mention of potential late e5ects sho&l# be part of the #isc&ssions! Achec$list with all areas to be co'ere# may help to be complete, an# is sometimesafterwar#s &sef&l if #isc&ssion6let alone liti%ation6 occ&rs! 7hil#ren sho&l# be

informe# accor#in% to their psycholo%ical a%e! The yo&n%er, the more importantis what is %oin% to happen imme#iately! The ol#er the patient, the more

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perspecti'e can be %i'en for the whole treatment! 8emember always thatlistenin% is more important e'en than tal$in%! 8emember why we ha'e two earsan# only one mo&th! Than it is also time to inform the referrin% #octor, be itanother pe#iatrician or a %eneral practitioner! 8e%istration of the new patient isan important tas$ too! 3f a research project is part of the treatment, informe#consent sho&l# be obtaine# from the parents, an# if possible form the chil#!

uring treatment

.or each treatment protocol not only the 9ow sheet sho&l# be a'ailable, b&t alsothe %&i#elines to that speci(c protocol! The resi#ent in char%e sho&l# st&#y these%&i#elines an# especially the parts rele'ant to the treatment phase he:she isresponsible for! .or each patient a c&m&lati'e s&mmary sho&l# be ma#e e'ery.ri#ay, so that the team that is in char%e #&rin% o5 ho&rs at ni%ht an# in thewee$en# can see in a short time all the rele'ant #ata! /pecial care has to beta$en for hy%iene, especially han# washin% an# cleanin% of instr&ments+stethoscope; an# of isolatin% the patient if he:she has low white co&nts +re'erseisolation as well as when a patient #e'elops an infection +isolation ! Oftentimesisolation an# re'erse isolation %o han#6in6han#! 3f the patient is #ischar%e# as&mmary of the clinical perio# sho&l# be ma#e an# #istrib&te# to the secretary of the pe#iatric oncolo%y center an# to the o&tpatient clinic,, an# where rele'ant tothe referrin% #octor!

$ollo%-up

<&rin% treatment it is important that the family is instr&cte# when an# where to

come bac$ for chec$s an#:or treatment! Also here, information sho&l# be %i'en tothe secretary:#ata mana%er! 3t is important to instr&ct the family what to #o if thechil# falls ill or #e'elops fe'er! "eas&res to be ta$en may #epen# on where thepatient li'es, at home far away, closer by or in the %&est ho&se! Also important ishow they tra'el) #o they ha'e a car, or are they #epen#ent &pon p&blic transport!After treatment is (nishe# it is necessary that families come bac$ for chec$6&p onlate e5ects, an# to ass&re that there is no relapse! This can be #one by simplehistory ta$in%, physical e amination an# basic laboratory wor$! 3n 3n#onesiacompliance with treatment is often a problem), ref&sal of treatment +parents ta$ethe chil# home before treatment , aban#onment +patients #rop o&t #&rin%treatment, or fail to a#here to protocol for more than a few wee$s as well as lossto follow6&p +no show after treatment is complete# ! 3n all these cases it is of&tmost importance to ha'e a means of reachin% the families! This is best #one bymobile phone, sms, b&t if nee#e# ho&se 'isit sho&l# be consi#ere#! The =P orlocal pe#iatrician may be as$e# to help in these matters!

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CHEC&'!(T "E) P*T!E"T( E(TE''* C'!"!CA"

B38T><AT>O/P3TA 8 =?A<"3//3O <AT

<3A= O/3/*TE !*G"O(!( &"O)"+ !(CU(( )!TH PE !*T#!C

O"CO'OG!(T TU O# .O*#>3/TO8@/ ""A8@P>@/37A

A"3 AT3O

'a/oratory e0aminations #esult inon+

>ematolo%y

>b, >t, ery, cell in#ices, *B7, #i5erentialco&nt, A 7, thrombocytes

Bloo#chemistry

78P, /8, a, C, 7l, 7a, P, "%, creatinine,rea, &ric aci#, A AT, A/AT, <>,

Bilir&bin, Alb&min7oa%&lation

PT, aPTT

.eces Parasite screenrine 7ells, %l&cose, protein! 7&lt&re only on

in#ication3nfection

parameters

<epen#s on clinic, for instance <i$$e

<r&ppel, "anto& , microbiolo%y c&lt&res,serolo%y T&mormar$ers

alpha6.etoprotein +%erm cell,hepatoblastoma-catecholamines +V"AD ne&roblastoma-

#adiology6thora AP an# lateral; 7hec$ me#iastinal mass,

heart sha#ow, l&n% (el#s/= Ab#omen, li'er spleen, t&mor, siEe an#

consistency, an# %&i#e# by clinic other/=

7T, "83 T&mor siEe an# local e tension, lymphno#e in'ol'ement

Procedures under sedation or in general anesthesiaB"P "orpholo%y, imm&nophenotypin%,

molec&lar biolo%y, cell ban$P) (rst P

always bymoste perience#

7ell co&nt, 7ytolo%y +as$ for presence ofle&$emic cells, an# n&mber oferythrocytes , %l&cose, protein!3f thrombocytes FG0,000) platelettransf&sion

TrephineBone +3f #ry tap B"P or in cases ofne&roblastoma , in sterile saline to

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Biopsy Patolo%i AnatomiOther in1estigations, consultations

7ar#iolo%y 7ar#iac /= if protocol containsanthracyclines

A&#iolo%y >earin% test if protocol contains platin&m

#r&%sPsycholo%y All families, +an# chec$ for researchproject

/&r%ery p front +; in all patients with soli#t&mors

&tritionist All patients who start on chemotherapy!nformation

.amily 3nfo stella 7linic, .low sheet protocol,informe# consent form for researchprojects an# for #ata collection, infoteam names

7ollea%&es /&mmary of #ia%nosis an# protocolE0tra1asation of cytostatic drugs2

To be complete# from the Cwaliteits et!

(upporti1e Care

Hydration ) =oal) to ass&re a#e &ate 9&i# inta$e! Often chil#ren arri'e athospital alrea#y a little #ehy#rate#! 8o&te) Oral:naso%astric t&be, intra'eno&s!"a imally 2,000 ml:m2:#ay! 3f i') a7l 0!4GI, =l&cose 2!GI with a##ition of C7l162 m"ol:#ay ! o C7l if t&mor lysis is possible!

Hyper-hydration+ =oal is to pro'i#e forced diuresis , to pre'ent $i#ney an#bla##er #ama%e by to ic pro#&cts from t&mor cells, or from cytostatic #r&%s+"ethotre ate, 7isplatin, cyclophosphami#e ! (o the inta3e is not the goal,/ut the rapid e0cretion2 Therefore precise 9&i# balance is essential! As soon asthe &rine pro#&ction becomes less, the inta$e sho&l# be lessene# too, otherwisethe patient will %et e#ema an# car#iac fail&re! <i&retics may be &se# to stim&latethe #i&resis e cept with 7isplatin!

!ndication

42 nephroto0ic medication+a! 7isplatin, 7arboplatinb! 3fosfami#e, 7yclophosphami#e +>emorrha%ic 7ystitisc! "ethotre ate + G00m%:m2

2! Possi/le tumor lysis syndromea! ewly #ia%nose# hematolo%ical mali%nancy, ne&roblastomab! 7hec$ 9&i# balance e'ery K ho&rs! 3nstr&ct n&rses to call

imme#iately if &rine pro#&ction falls!c! Bo#y wei%ht at least #aily to chec$ for 9&i# o'erloa#!#! Physical e amination at start e'ery shift to chec$ for e#ema an#

p&lmonary rales +l&n% e#ema

*dministration

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1! Orally +ma G00ml:m2:#ay , naso%astric t&be, intra'eno&sly orcombination!

2! Total 'ol&me H,000 ml:m2:#ay, ma imally G,000ml:#ayH! 3ntra'eno&sly a7l 0!4GI %l&cose 2!GID C7l a##ition 162""ol:$%:#ay4! 3n case of t&mor lysis prophyla is +hyperhy#ration no a##ition of C, 7a

an# P, beca&se these will be release# by #isinte%ratin% mali%nant cells,an# may be retaine# by $i#ney f&nction problems;

Cisplatin, Car/oplatin

1! /tart hy#ration 4 h before start platin&m compo&n#2! Post6hy#ration 24h after stop platin&m compo&n#H! 7isplatin is contra6in#ication for &se of #i&retics since nephroto icity may

increase, in this case mannitol is &se# to achie'e force# #i&resis +seebelow ! 3f cisplatin is %i'en as 24 ho&r contin&o&s inf&sion, mannitol is notnee#e#!

4! 8enal t&b&lar #ama%e may res&lt in loss of electrolytes! Therefore chec$ser&m 7a, P, a, C an# "% an# of co&rse &rea an# creatinine at least once#aily, before an# after the chemo co&rse!

G! After a co&rse of 7isplatin, prescribe "% s&ppletion +for instance "% 7itrateK0m%:$%:#ay in three #oses !

Cyclophosphamide 56788mg m9 course:, !phosphamide

1! Pre6hy#ration H ho&rs2! Post6hy#ration 24 ho&rsH! " / A is %i'en to pre'ent hemorrha%ic cystitis) #osa%e same #ose in

milli%rams as 7yclo:3fosfami#e pl&s H0I of this #osa%e as a p&sh beforestart! /o if for instance cyclophosphami#e #osa%e is 1!000m%:m2, then" / A p&sh is %i'en HG0m%:m2 before start 7yclophosphami#e an#followe# by 1,000m%:m2:#ay contin&o&s inf&sion #&rin% 24 ho&rs!Alternati'ely, instea# of contin&o&s inf&sion, " / A may be %i'en in H#i'i#e# #osa%es per #ay as bol&s inf&sion!

4! 3f 7yclo:3fosfami#e is %i'en on se'eral consec&ti'e #ays, the loa#in% #oseof H0I m&st be omitte# on secon# an# followin% #ays!

G! aboratory chec$ &rine e'ery portion 'oi#e# for erythrocytes +if &sin%stic$s be aware that the $etone reaction will also be false positi'e; ! 3fmicroscopic hemat&ria is #e'elopin% contin&e " / A an# hyperhy#ration!3f 'ery painf&l an# clots of bloo# are obser'e# in the &rine, there may bein#ication to rinse the bla##er with a sol&tion of " / A!

T; 56<88mg m9:

1! Pre6hy#ration 4h before a#ministration of "T2! /tart al$aliniEation also 4 h before "T to $eep p> of &rine L b&t not

more than p> M!G; Prescribe a>7OH +4!2I 120ml:m2:#ay contin&o&s i'!3ncrease by 20I if &rine p> FL!0! "eas&re &rine p> at e'ery portion &rine'oi#e#!

H! Post6hy#ration &ntil 24h after (nishin% "T inf&sion +b&t see also Aprotocol

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4! e&co'orin) life sa'in%; 3f #elaye# or for%otten, #eep bone marrow aplasiaan# se'ere m&cositis will #e'elop! /ee below

annitol

• 3n#ication) cisplatin, since #i&retics are contra6in#icate#, mannitol is &se#for force# #i&resis

• 3f cisplatin is %i'en as 24h contin&o&s inf&sion, mannitol can be omitte#!• 3f the protocol #oes not prescribe e act &se of mannitol &se "annitol 20I

+200m%:ml an# prescribe L!Gml:m2:ho&r! /tart 4 h before start cisplatinan# stop Kh after stop cisplatin!

'euco1orin

• /ee respecti'e protocol for #etails!• ssential to pre'ent si#e e5ects of "T , so start the =rst dose e0actly

on time>>>• 7hec$ creatinine before start "T an# 24h after start "T ) if 2 initial

'al&e at 24h after start "T ) #o&ble the #ose of e&co'orin!

Eye drops

• To pre'ent chemical conj&ncti'itis• 3n#ication) >i%h <ose Ara67 can res&lt in chemical conj&ncti'itis by

e cretion of A8A67 in tears 9&i#! Also the cornea may be a5ecte#! 8es&lt ispain an# photophobia an# re# conj&ncti'ae!

• "e#ication eye #rops with 0!1I #e amethasone, prescribe 4##2#rops inboth eyes!

• 3f still pain a## #iclofenac 0!1I eye #rops +H## 2 #rops each eye• Literature: Matteucci et al.: Topical prophylaxis of conjunctivitis induced by

high dose Cytosine Arabinoside. Haematologica !!"#$%: &' &(

Progestati1es and $ertility

*im+ to s&ppress menstr&ation to pre'ent bloo# loss an# &nnecessary bloo#transf&sions

edication+

• 7ons&lt %ynecolo%ist is a %oo# i#ea! Pro'era N pro%esterone! Prescribe 1## Gm%, an# increase to 10 m% if still

&terine bloo# loss! <isa#'anta%e) it is not contracepti'e; "icro%ynon or similar) prescribe #ayly, witho&t the &s&al stoppin% of G

#ays beca&se then with#rawal blee# will occ&r, which we wo&l# li$e topre'ent, especially if there is also thrombocytopenia; <isa#'anta%e isincrease# ris$ of thrombosis, so combination with 6Aspara%inase is not a%oo# i#ea! A#'anta%e) anticoncepti'e!

&crin + >r> anta%onist 3f a'ailable only after cons&lt %ynecolo%ist!

$ertility preser1ation

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.ertility will normally not be impaire# with protocols for A , > , *ilm s T&moran# lower ris$ on6>o#%$ins ymphoma! 7yclophosphami#e more thanc&m&lati'e 4%:m2 will impair fertility of both men an# women, with almostin'ariable infertility at c&m&lati'e #oses abo'e 12%:m2 ! *ith more intensi'echemotherapy the ris$ of infertility of co&rse will increase!

3n yo&n% males, sperm preser'ation +cryopreser'ation before startchemotherapy is a possibility! >owe'er, in the %ro&p of boys with a #ia%nosis ofmali%nancy the yiel# is often #isappointin%! 7ons&lt the fertility center +if presentin yo&r hospital !

.or yo&n% females there is presently no %oo# sol&tion! O'arial tiss&e may becryopreser'e#, an# re6implante# after s&ccessf&l treatment! B&t this is stille perimental with low %ra#e of s&ccess! An# for females with le&$emia orlymphoma it is not possible, beca&se the o'aria are consi#ere# a sanct&ary sitecontainin% mali%nant cells!

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*nti-emetic therapy

!ndication+ Ta/le 4

osage+ Ta/le9

Ta/le 4+ !ndications for anti-emetics"on-emetogenic 'o% emetogenic edian

emetogenicHighemetogenic

7yclofosfami#eFG007ytarabine FG0K"P"T F1%ramPre#nisone<e amethasoneVincristine

6Aspara%inase7yclofosfami#e

G00>y#ro y6&rea

7ytarabineG0F1000

<actinomycinetoposi#e

3matinib3ntrathecalme#ication"T 1%ram

Anthracyclines7arboplatin7isplatin3fosfami#eProcarbaEine

(tep 4 (tep 4?9 (tep 4?9?may/e @

(tep A andmay/e @

Ta/le 9+ (tep%ise schedule for anti-emetic measures(tep rug osage #emar3s

4 On#ansetron Gm%:m2:#ose, po or i', ma H ##,ma Mm%:m2 #ose! A#minister H0min&tes before (rst chemo

9 <e amethasone

0!1m%:$% i!'!, 26H ##+ma 2m%:per #ose, H0 min&tesbefore chemo

A'oi# in case ofA" or braint&mors

@ oraEepam 1!Gm%:m2 po or i', 162 times per #ay 3f psycho%eniccomponent! /tarte'enin% beforechemo

A Aprepitant+ men#

B/A F 1!2m2)1 st #ay) M0m% orally, 1 ho&r beforechemo

e t #ays) 40 m% in the mornin%B/A 1!2m2)1 st #ay) 12Gm% orally, 1 h beforechemo

e t #ays) M0m% in the mornin%

.or hi%hlyemeto%enic an#therapy resistant

'omitin%! A## tostep 1 an# 2

< 8ela ation /ome teena%ers $eep 'omitin%!/ometimes anti6emetic ha'e oppositee5ect! 8ela ation, #i'ertin% attention,rea#in% a boo$, %i'e patientattention, all may help won#erf&lly

3f stron%psycho%eniccomponent!

specially yo&n%la#ies may

bene(t by thisapproach!

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Tumor 'ysis (yndrome

General remar3s

3nitial chemotherapy in some chemosensiti'e mali%nancies li$e A , > ,

sometimes A" , an# rarely ne&roblastoma may lea# to rapi# lysis of cells! 'enbefore chemotherapy spontaneo&s t&mor lysis may lea# to problems! Theseproblems are ca&se# by massi'e release of &ric aci#, C an# P, with res&ltant

• Precipitation of &ric aci# an# 7a6Phosphate in the $i#neys• 8es&ltin% in hyper$alemia• >yperphosphatemia• 3mpairment of renal f&nction!

Chec3s• 7lose monitorin% of 9&i# balance e'ery K ho&rs• "onitor bo#y wei%ht an# physical e amination +e#ema- rales-• ab 162 #ayly) a, C, 7a, P, "%, creatinine, &rea, &ric aci# +if rasb&ricase is

%i'en, bloo# t&be on ice, an# cito to lab, beca&se rasb&ricase will#isinte%rate &ric aci# by its enEymatic action e'en in 'itro

Prescriptions

>yperhy#ration +Hliter:m2:#ay, ma G liter:#ay ) to pro'i#e a#e &ate

#i&resis +force# #i&resis an# so pre'ent precipitation in the $i#neys! Allop&rinol! 3t is a anthine o i#ase inhibitor an# th&s bloc$s the pro#&ction

of new &ric aci#! /tart at least 24 ho&rs before chemotherapy to%etherwith hyperhy#ration! <osa%e 2006H00m%:m2:#ay in 26H #oses

3f a'ailable) in cases with hi%h probability of t&mor lysis syn#rome +>8 Amainly ) ricase +8asb&ricase brea$s #own &ric aci#! The &ric aci# le'elwill #rop 'ery &ic$ly! 3t is a 'ery powerf&l inhibitor of the t&mor lysissyn#rome!<osa%e) 1 'ial +N 0!1Gm% per 10$% bo#ywei%ht per #ay, intra'eno&sly!8o&n# o5 at f&ll 'ials +#o not throw away this e pensi'e #r&%; ! >as to %oto%ether with hyperhy#ration! /top if &ric aci# 'al&es are normaliEe#! olon%er than L #ays! "ost fre &ent si#e e5ects) fe'er +; na&sea, 'omitin%,aller%ic reactions!

• A'oi# a##ition of C, 7a or P in the intra'eno&s 9&i#, &nless clinical an#laboratory e'i#ence of hypo6C, hypo67a or hypo6phosphatemia!

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General ad1ice for lifestyle to 3eep until @ months afterstop chemo2

• *ash han#s fre &ently, an# learn how to #o this properly!• A'oi# as m&ch as possible contact with lar%e %ro&ps of people!• =o to school or crQche as &s&al, important to feel better;• A'oi# payin% in m&# or san# where animals may ha'e e crete#!• o &ncoo$e# meat, (sh or similar! *ash any fr&it or 'e%etables thoro&%hly!• 7ertainly a'oi# contact with anyone who is fe'erish or ill!• o ris$y sports in case of thrombocytes lower or pre#icte# lower than

G0,000!• 3n case of fe'er + hi%her than HM!G7 once or hi%her than HM!07 twice with 1

ho&r inter'al imme#iately contact the clinic, at all times of #ay an# ni%ht!

<o not wait &ntil ne t mornin%;• "o&th caps are &seless an# sti%matiEin%, so we #isco&ra%e its &se! "o&th

caps may be &se# by persons aro&n# the patient who ha'e a co&%h orapparent airways infection +e'en here, han# washin% is more importantthan mo&th caps

Hand %ashing is of eminent importance, /oth for the patient andfor anyone in close contact %ith the patient2

Use common sense to pre1ent attracting infections fromsurroundings and surrounding persons>

P*!"General2

T%o types of pain+

"ocicepti1e+ somatic, p&lsatin%, 'isceral, well localiEe#, crampin% "europathic+ peripheral +Vincristine ne&ropathy or centrally in#&ce#

+phantom pain

Etiology of pain+

Tumor related !o Tiss&e #ama%eo Bone marrow or bone in(ltrationo 7ompression of or%anso 7ompression of ner'eso 3ncrease# intracranial press&re

Chemotherapy )or radiotherapy* relatedo "&cositiso 3nfectio&s

+rocedural paino Bone marrow p&nct&reo Bone an# other biopsyo &mbar p&nct&re

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o Venip&nct&re

*dditional factors aBecting pain sensation

• /&bjecti'eo A%e an# psycholo%ical #e'elopmento 7&lt&ral factorso arlier e perience an# history of pain

• Objecti'eo <epressiono An ietyo Tire#nesso /leeplessness

#elie1ing pain

Pain can be #escribe# as mil#, se'ere or 'ery se'ere! .or many chil#ren the painscale + L or 10 steps with the faces la&%hin% +no pain to cryin% +'ery se'erepain an# all emotions in6between can be of help to #eci#e the se'erity! "othersan# fathers may be able to j&#%e, b&t sometimes they are too a5ecte#themsel'es to be able to score a#e &ately! "ost n&rses will be able to #o that,listen to them;

Proce#&ral pain can be re#&ce# immensely by %oo# information, &iets&rro&n#in%s, %oo# preparation, an# %oo# earlier e perience;;; se of s&rfaceanti6pain meas&res +li#ocaine spray, mla +Nli#ocain R prilocain plaster an#similar may also be helpf&l!

Phase 4+ mild painParacetamol Oral +ta$es 16

2h8ectal +ta$esHh

1061Gm%:$%:#ose206H0m%:$%:#ose

"a K##"a 4##

"a 1,000m%:#ose"a 4,000m%:#ay

Phase 9+ (e1ere pain Trama#ol Oral

8ectal162m%:$%:#ose162m%:$%:#ose

"a 4##"a 4##

o #aily ma

ar%e therape&tic spectr&m) #ose may be increase# &ntil e5ecti'e! 7a&tion)hi%her #oses may in#&ce na&sea an# 'omitin%, so %i'e anti6emetics as nee#e#!7ancer Pain - - - -Phase @+ 1ery se1ere pain "orphine

.entanyl

Oral8ectal3V +or scPlaster

0!Hm%:$%:#ose0!Hm%:$%:#ose

/ee pharma

K##K##

As perbijsl&iter

3ncrease &ntile5ecti'e! oma im&m#ose

• "orphine 4Gm%:#ay e &als abo&t .entanyl plaster12!Gmicro%ram:ho&r

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• "orphine an# morphinomimetics ha'e no &pper limit• 7ross tolerance is rare, so switch from one

morphinomimetic to another may be &sef&l!• =i'e j&st before pain will worsen, as for instance with

mo&th wash in m&cositis, or before proce#&res• "orphine ca&ses obstipation, so always combine with

la ans• /i#e e5ects) obstipation, na&sea, 'omitin%, itchin%!• Paracetamol combines e cellent with "orphine, always

combine them to limit #osa%es an# si#e e5ects!• e&ropathic pain may %et worse from morphine

*d u1ant therapy/A3<

+#iclofenacOral:rectal 16Hm%:#ose 264## "a

200m%:#ay,thrombopeniais contra6in#ication

oraEepam Oral:rectal 0!01m%:$%:#ose

H64## an iolytic

=abapentine Oral Gm%:$%:#ay <ay1) 1#ose,#ay2) 2 , thenH##

3n cases ofne&ropathicpain, titrate toma HGm%:$%:#ay

*''E#G!C #E*CT!O"(2

"ay 'ary from s$in rash, fe'er, breathin% problems to hypotension an# #eath!

7a&ses)

• "e#icines, li$e Aspara%inase, toposi#e, 8it& imab, antibiotics• Bloo# pro#&cts• 7ontrast 9&i#•

.oo# aller%y, insect stin%s etcetera8is$ factors)

• >ypersensiti'ity reactions before• <r&% has been &se# before• /e'erity of reactions my increase o'er time• Patients with aller%ic constit&tion li$e asthma

Pre'enti'e an# copin% meas&res, prepare an alleric $it that is a'ailableimme#iately)

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• Antihistamine +clemastine i!'! for instance, 0!02Gm%:$%:#ose, ma 2m% per#ose

• >y#rocortisone i!'! +4m%:$%:#ose• A#renaline +0!01m%:$% i!'! or i!m! /ol&tion of 1m%:10ml is 0!1m%:ml so

%i'e 0!1ml:$%• a7l 0! I, +rapi# (ll i!'! 20ml:$% an# may be repeate#

Treatment of apparent aller%ic:anaphylactic reaction)

• /top inf&sion of the o5en#in% #r&%!• =i'e antihistaminic• 3f no e5ect in 1G min&tes %i'e hy#rocortisone

Treatment of se'ere anaphylactic reaction) 7hec$ A, B, 7

A) 8espiratory) o ob'io&s &pper airways obstr&ction) %o to B

• /tri#or +hi%her airway obstr&cte# )o =i'e a#renalin i!m!o As$ bystan#er to call intensi'ist teamo O2 100I thro&%h non6rebreathin% mas$o eb&liEe Gml A#renalin sol&tion 1)1000o /e'ere obstr&ction call T specialist for int&bation for cricotomia

• B) 8espiratory) bronchial obstr&ction +wheeEin%, lower airways obstr&ctionif clear %o to 7

o A#renalin i!m!o /alb&tamol neb&liEation +F4y 2!G m%D 4y G!0 m%o O2 100I non rebreathin% mas$ if a'ailable

• 7) circ&latory, no problem) repeat physical e amination, monitoro >ypotension or e'en shoc$)o As$ bystan#er to call reanimation teamo .ill with a7l 0! I 20ml:$% rapi# inf&siono O2 100I by bon rebreathin% mas$o A#renalin i!m!o 3nsert secon# i!'! line or intra6ossal nee#leo 8epeat (llin% with a7l 0! I 20ml:$%o 7hec$ heart rate +physical an#:or monitor an# start reanimation if

no p&lse!

". rechec3 e1ery fe% minutes *, . and C to e1aluate the eBect oftherapy2

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*drenocortical insuDciency

3ntro#&ction)

• specially in A %l&cocorticoi#s are wi#ely &se#!• An important si#e6e5ect is s&ppression of the hypothalamic6a#renal a is!

This is ca&se# by s&ppression of 78> an# A7T> pro#&ction! 3n the lon% r&n,the a#renal cortisone pro#&cin% cells atrophy, while the al#osteronepro#&ction remains &na5ecte#!

• 3f cortisone pro#&ction is s&Scient &n#er normal con#itions, it may beins&Scient &n#er stress! 3n this case a stress re%imen co&l# an# sho&l# be&se#!

• 3f cortisone pro#&ction is ins&Scient in basal con#ition, replacementtherapy with hy#rocortisone is to be consi#ere#, altho&%h it will f&rthers&ppress the a#renocortical a is!

3n#ication for s&bstit&tion therapy)

• This is only to be consi#ere# in patients with clinical e'i#ence ofa#renocortical ins&Sciency in combination with ser&m cortisol FM0nmol:lmeas&re# at #awn!

• /&bstit&tion therapy is hy#rocortisone 1061G m%:m2:#ay in three #oses#i'i#e# as 2)1)1

• 3f this is nee#e# it sho&l# ne contin&e# an# then tapere#• Taperin%) %i'e only the mornin% #ose of G6L!G m%:m2:#ay for 4 wee$s,

hal'e this #ose for the ne t 4 wee$s an# hal'e a%ain ne t 4 wee$s an#

stop!3n#ication for stress sche#&le)

• Patients who are on maintenance with hy#rocortisone• Patients who ha# %l&cocorticoi# treatment #&rin% at least 2 consec&ti'e

wee$s at a #ose le'el of 1Gm%:m2:#ay cortisone e &i'alent +see below• &i'alent #oses are appro imately)

o <e amethasone 1m%o "ethylpre#nisolone Gm%o Pre#niso+lo ne Lm%o

>y#rocortisone 2Gm%• /tress sche#&le is strati(e# into mo#erate:se'ere:A##ison crisiso "o#erate stress) li$e low %ra#e fe'er, 'iral infection, #entistry!

>y#rocortisone H064G m%:m2:#ay, #i'i#e# into 4 #osesPre#nisone 10 m%:m2:#ay, #i'i#e# into H #oses

o /e'ere stress) li$e hi%her fe'er, witho&t +pre6 shoc$, tra&ma>y#rocortisone G06LG m%:m2:#ay #i'i#e# into 4 #osesPre#nisone 1G m%:m2:#ay #i'i#e# into H #oses

o A##ison crises) si%ns of +pre6 shoc$Bol&s >y#rocortisone i!'!D F1y 2G m%D 16Ky) G0m%D Ky) 100m%!

.ollowe# by) >y#rocortisone 100 m%:m2:#ay i!'! #i'i#e# into 4#oses

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Other meas&res accor#in% to clinical state re%ar#in% shoc$!o Anesthesia an# /&r%ical proce#&res)

"inor) an# only nee#e# with pro'en a#renal ins&Sciency)• J&st before anesthesia) Pre#nisone Mm%:m2 i!'!• /ame #ay) another M m%:m2 #i'i#e# into 2 #oses• .irst +sometimes also secon# postoperati'e #ay) 12

m%:m2:#ay #i'i#e# into H #oses"ajor) li$e laparotomy)

• J&st before anesthesia) Pre#nisone 12m%:m2 i!'!• /ame #ay) 12 m%:m2 #i'i#e# into 2 #oses• .irst +maybe also secon# postoperati'e #ay) 1G

m%:m2:#ay #i'i#e# into H #oses

VE"O-OCC'U(!VE !(E*(E 5VO :

!ntroduction

VO< is res&lt of #ama%e to en#othelial cells in the li'er! The ris$ to #e'elopit is hi%her in persons with a history of hepatitis! 7hemotherapy, an# especially"elphalan, B&s&lphan an# other intensi'e chemotherapy can ca&se it! 3fVincristine is combine# with aEole antif&n%als, it is almost s&re to happen! Beaware;

The diagnosis VO< is a clinical one, base# &pon a trias) the (eattle Criteria+

1! hepatome%aly +often painf&l ,2! hyperbilir&binemia G times normal 'al&e,

H! wei%ht %ain + GI thro&%h ascites! 3f in #o&bt, /= may help, by ascertainin% #iminishe# 9ow or e'en re'erse# 9owin the 'enae portae, with ascites in the ab#ominal ca'ity! A (nal proof may be%aine# thro&%h a li'er biopsy an# Patholo%ic e amination! This may be #one ifthe patient #ies an# the #ia%nosis is not 100I clear! 3t can then be #one witho&ta f&ll post mortem a&topsy! o more problems than Bone "arrow P&nct&re whichmost patients ha'e &n#er%one anyway!

The treatment of VO

•

limit 9&i# inta$e to L06M0 ml:$%:#ay +incl&#in% transf&sions an#me#ication;• .&rosemi#e 1 m%:$% i!'! in 26K #oses per #ay• /ol#acton 26K m%:$% i!'! one #ose per #ay• Ceep thrombocyte co&nt abo'e G0,000• <e(broti#e if a'ailable) 2G m%:$%:#ay i!'! inf&sion s o'er 2 ho&rs• /trict $eepin% of 9&i# balance an# a#aptin% 9&i# inta$e on it!

UCO(!T!(

!ntroduction

Pa%e 1K



3n'asi'e infections are common, beca&se the m&cosal barrier is bro$en, an#ne&tropenia is almost always present in cases of se'ere m&cositis! e&tropenicfe'er has to be treate# imme#iately! e&tropenic enterocolitis +typhlitis is a life6threatenin% complication! =&i#elines for ne&tropenic fe'er an# typhlitis area'ailable separately from this #oc&ment!

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P#OPH '*;!( of .*CTE#!*' *" $U"G*' !"$ECT!O"(

!ndication+

• probable ne&tropenia of lon%er #&ration + 10 #ays

edication+

• 7e( im• 7ipro9o acin, H0m%:$%:#ay in 2 #oses +ma 1200 m%:#ay• 3traconaEole! K m%:$%:#ay, once #aily as sol&tion +ma 400 m%:#ay

o 3traconaEole sho&l# ne'er be %i'en in sche#&les containin%'incristine! The combination is se'erely hepatoto ic an# ne&roto ican# can be fatal! 3nteraction with other i!'! me#ication is alsopossible since 3traconaEole is a stron% inhibitor of 7@PHA, so many#r&%s which are metaboliEe# by this pathway will reach to ic le'els!

Therefore itraconaEole sho&l# better not be %i'en with anyintra'eno&s chemotherapy!

• Ceto$onaEole ) stop #&rin% chemo #ose -• Alternati'e me#ications may be)

o .l&conaEole, G m%:$%:#ay once #aily +ma 400m%:#ay also ame#i&m stron% 7@PHA inhibitor with a lon% half life, ca&sin% hi%herle'els of many #r&%s +see pharmacopae !

o 7olistine, L!G m%:$%:#ay in H #oses +ma M00 m%:#ayo Tobramycine, Mm%:$%:#ay in 4 #oses +ma H20 m%:#ayo Amphotercin B, as sol&tion +potion 10 m%:$%:#ay in H #oses +ma

M00 m%:#ay

P"EU OC (T!( P#OPH '*;!( 5PCP:

!ntroduction

Pne&mocystis jiro'eci +formerly pne&mocystis carinii is a f&n%&s! .ormerly it wastho&%ht to be a protoEoan! 3t ca&ses interstitial pne&monia in imm&no#e(cienthosts! Patients at ris$ are all those with prolon%e# lymphocytopenia! 3t &se# to bea fatal complication in patients with A ! B&t it can also occ&r in > , A" an#after lon%er #&ration corticosteroi# me#ication! /ince it was #isco'ere# that low#ose co6trimo aEol is e5ecti'e in pre'ention, P7P pne&monia is rarely seenanymore! 3f co6trim cannot be &se# +aller%y for instance Pentami#ine is alsoe5ecti'e!

edication

• 7o6trimo aEol 1GRH m%:$%:#ay in one #ose on H #ays per wee$! These #aysmay be H consec&ti'e #ays or alternatin% #ays! 3f aller%y, or if bone marrow#epression is a problem +cotrim is mil#ly myelos&ppressi'e pentami#inecan be &se#!

• Pentami#ine i!'! one #ose of 4 m%:$% i!'! e'ery 4 wee$s•

Pentami#ine neb&liEation) M m%:$% e'ery 4 wee$s +ma H00 m%uration of medication

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• /tart after in#&ction of A• /top #&rin% ><"T +interaction with renal clearance• 7ontin&e &ntil H months after cessation of maintenance chemotherapy

(T#EPTOCOCCU( V!#! *"( P#OPH '*;!(

!ntroduction

/trep 'iri#ans is a common low patho%en in the oropharyn ! 3n se'erelyne&tropenic patients it can ca&se f&lminant sepsis with A8</! Prophyla is isespecially important in A" patients! "icrobial c&lt&res to trace antibioticresistant strains is important!

!ndication

• .ollowin% ><6A8A67 + 1000 m%:m2:co&rse• <eep ne&tropenia of +e pecte# lon%er #&ration• "&cosytis an# ne&tropenia

edication

• Penicillin6=) K0,000 3 :$%:#ay i!'! in 4 #oses• .eniticillin) 1G m%:$%:#ay orally in 2 #oses• Amo icillin) 2G m%:$%:#ay in one #ose• 3n cases of resistance to the antibiotics

o Vancomycino Teicoplanino 7laritromycin

uration of medication

/tart after chemotherapy co&rse an# contin&e &ntil *B7 G00 an# A 7200

HE#PE( (! P'E; 5H(V: P#OPH '*;!(

!ndication+

• patients who ha'e ha# stomatitis:m&cositis at prior chemotherapy, an#>/V has been #emonstrate# +if possible !

edication+

• Valacyclo'ir H0 m%:$%:#ay orally in 2 #oses +ma 1,000 m%:#ay

V*#!CE''* T#E*T E"T *" P#OPH '*;!(

!ntroduction2

Varicella oster Vir&s +V V, chic$en po is a relati'ely harmless infection inhealthy chil#ren! 3t is the same 'ir&s that ca&ses >erpes oster! 3n patients on

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chemotherapy it is life threatenin%, especially thro&%h V V pne&monitis! Alle5orts sho&l# be #one to pre'ent this 'ir&s %oin% ro&n# the war# +see /tefan&s,

Asian Pac J Cancer Prev. 2010;11(2):289-92 ! Vaccination is possible, b&t has pro'en to be#an%ero&s in imm&no#e(cient patients!

Pre1ention

All members of pe#iatric oncolo%y team nee# to be aware of the #an%er ofchic$en po ! 3t is conta%io&s from a few #ays before the (rst blisters appear &ntilG #ays after , an# as lon% as the blisters are not t&rne# to #ry cr&sts! The stat&sof personnel +imm&ne or not is important to $now! Any person with possible V V+incl&#in% those with herpes Eoster sho&l# be $ept o&t of contact with chil#renon chemotherapy, an# patients with V V infection sho&l# be strictly isolate#! 3fa'ailable, V V hyperimm&ne ser&m sho&l# be &se# to protect non6imm&nepatients who ha# contact with V V!

edication+

• 8ecent contact +F K h )o V V hyperimm&ne ser&m i!m! +or s!c in case of thrombocytopeniao Valacyclo'ir H0 m%:$%:#ay orally in 2 #oses

• 7ontact more than K ho&rs a%o)o Valacyclo'ir K0 m%:$%:#ay in 2 #oses +"a H,000 m%:#ay

• <&ration) &ntil 2M #ays after contact!• 3f clinical symptoms +e anthema, blisters still occ&r

o Acyclo'ir H0 m%:$%:#ay in H## i!'!o Valacyclo'ir 0 m%:$%:#ay orally in H #oses +ma H,000 m%:#ayo Postpone chemotherapy &ntil s$in rash has cleare# +cr&sts may still

be present

V*CC!"*T!O"

The &s&al 'accinations ha'e to be postpone# #&rin% chemotherapy! One the onesi#e beca&se it is #o&btf&l whether they will res&lt in imm&nity in 'iew of theimm&nos&ppresse# state, on the other han# beca&se 'accination with li'eatten&ate# strains may still ca&se se'ere #isease! This happene# for instancewith Varicella oster 'accination!

The 'accination pro%ram howe'er has to be pic$e# &p a%ain H months after stopchemotherapy! /o all 'accinations that ha'e been s$ippe# sho&l# then be %i'en!

A special sit&ation may occ&r with 'ery intensi'e chemotherapy, as in+a&tolo%o&s stem cell +re inf&sion! Thes patients nee# re6'accination e'en if theyrecei'e# all 'accinations alrea#y as sche#&le#!

$E.#!'E "EUT#OPE"!*

(EE (EP*#*TE P#OTOCO' 5 or insert here

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.'OO P#O UCT(, G#O)TH $*CTO#(

!ntroduction

All bloo# pro#&cts sho&l# be (ltere# to limit the possibility of 'iral infections! 3fpossible, irra#iate# pro#&cts sho&l# be &se#, in cases of intensi'e myeloablati'etherapy +stem cell transplantation b&t also in case of family #onors +; ! Patientswith +cell6me#iate#, T6cell imm&no#e(ciency sho&l# also ha'e the bloo#pro#&cts irra#iate# to pre'ent =raft6'ers&s6>ost <isease +='>< !

Erythrocyte concentrates, Pac3ed #ed Cells 5P#C:

!ndication+

• 7linical e'i#ence of anemia• Transf&sion limits) see below• e'er %i'e &nnecessary transf&sions• Always or#er ba%s so that nothin% has to be #iscar#e#

o .or instance if patient nee#s H00ml, an# a ba% is 2G0 ml) or#er oneba%, not two!

Transfusion limits

• 3n a patient in %oo# con#ition, no fe'er, no infection) >b F K!0%:#l +4 mmol:l

• 3n a patient in %oo# con#ition b&t before a chemo co&rse) >b F L!G%:#l +G mmol:l

•

3n a sic$ patient, s&spicion of sepsis) >b F !0 %:#l +Kmmol:l

Ho% much and ho% fast

• 3f chronic, #&rin% chemotherapy) 1061G ml:$% +ro&n# o5 at the nearestlower n&mber of ba%s in 46G ho&rs, chil#ren 40 $%) 2 ba%s only!

• 3f bloo# loss +li$e %astro6intestinal blee#in% ) start with 1061G ml:$% an#inf&se as &ic$ly as possible! Or#er more ba%s if blee#in% is still inpro%ress! 8emember that =3 bloo# loss can be massi'e, witho&t m&chbloo# appearin% in the stools;

TH#O .OC TE T#*"($U(!O"(

!ndications

• 3f manifest blee#in% in thrombocytopenic patients• 3f a s&r%ical proce#&re or P is planne# in thrombocytopenic patients

Transfusion limits

• Prophylactic +A" , sepsis F 20,000• Prophylactic insertion =T F 20,000• Prophylactic) (rst P in A , A" F G0,000• Prophylactic later P s F 20,000

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• Prophylactic +se'ere m&cositis F G0,000• Therape&tic, acti'e blee#in% F G0,000• 3ntracranial blee#in% F 100,000

Ho% much and ho% fast

• One #onor &nit per 10$%, fast inf&sion &nless circ&latory o'erloa#threatens

• e'er throw away thrombocyte s&spensions +or any bloo# pro#&ct for thatmatter &nless there is a transf&sion reaction! 3n that case stop imme#iatelan# sen# ba% bac$ to bloo# transf&sion ser'ice for analysis +they may as$a bloo# sample frm the patient to analyEe antibo#ies

G#*"U'OC TE T#*"($U(!O"(

/till e perimental an# not yet e'i#ence base#! 8is$s are consi#erable

G-C($ 5 "EUPOGE", $!'G#*(T! , ETC:

"ay be &se# in life6threatenin% infections in ne&tropenic patients, sepsis,f&n%al p&lmonary infections +Asper%ill&s

8an#omiEe# blin#e# placebo controlle# trial in /t6J&#e s /A showe# abo&t24 ho&rs earlier appearance of ne&trophils in the circ&lation, b&t no e5ecton morbi#ity or mortality whatsoe'er! +P&i 7>) n%l J "e#!1 LDHHK)1LM16L =67/. may increase the ris$ of secon#ary A" +8ellin%"V) Bloo#! 200HD101)HMK26L

3t is e pensi'e, parenteral a#ministration necessary!

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E*#' *" '*TE TO;!C!T

C*# !OTO;!C!T

Anthracyclines are the most car#ioto ic #r&%s! 7ombination with ra#iotherapyincreases this problem! To icity may alrea#y appear #&rin% therapy, b&t it may#e'elop years later! 7ar#ioto icity is #ose6relate#, b&t yo&n%er chil#ren an#females tolerate smaller #oses, an# there is probably interaction with some 'iralinfections too!

"eas&res to limit anthracycline car#ioto icity ha'e trie#) inf&sion o'er lon%erperio#s +1624 ho&rs , an# a##ition of a chemoprotector +#e raEo one , b&t noneof these are ro&tine! 3nf&sion o'er at least 1 ho&r is a#'ocate#, if only to #etectearlier e tra'asation, an# so limit 'asc&litis an# necrosis!

arly #ia%nosis of incipient car#iac #ama%e is important, it allows for pre'entin%

f&rther #eterioration by stoppin% the &se of anthracyclines! 3t is a %oo# i#ea toha'e a car#iac /= meas&rin% at least the shortenin% fraction +/. an# repeatthis when a certain threshol# is passe#! .or #o or&bicin this is a lifetimec&m&lati'e #ose of 240m%:m2!

To chec$ for late e5ects, many clinics ha'e a policy to repeat car#iac /=ann&ally! >owe'er, not m&ch can be #one if to icity appears! >a'in% sai# this, ofco&rse if clinical si%ns of heart fail&re occ&r, certainly #ia%nostic tests arin#icate#!

"EU#OTO;!C!T

Complications from disease

e&rolo%ical symptoms often occ&r in brain t&mor patients an# sometimes inA ! A s &int in a patient with A , or any cranial ner'e palsy is ta$en ase'i#ence of menin%eal in'ol'ement an# nee#s treatment a#aptation!

7on'&lsions +(ts may res&lt from the t&mor itself or from infections an# frommetabolic #ist&rbances!

"yelocompression from ne&roblastoma +#&mbbell t&mors , chloroma, or A

#eposits are a me#ical emer%ency! <e amethasone may help b&t is often notf&lly e5ecti'e! e&ros&r%ical a#'ice an# e'ent&al treatment is man#atory!

7erebro'asc&lar complications in A" "H is also a me#ical &r%ency!

Complications from treatment

Ac&te ne&rolo%ical symptoms may occ&r after intrathecal a#ministration as wellas after chemotherapy with A8A67, 3fosfami#e an# "T ! ower ser&m alb&minmay increase the ris$ beca&se ther is more free #r&% in the circ&lation+3fosfami#e for instance !

7erebro'asc&lar inci#ents may occ&r after 6Aspara%inase therapy, infections an##i5&se intra'asc&lar coa%&lation +<37

Pa%e 24



e&coencephalopathy has been #escribe# after hi%h #ose A8A67m hi%h #ose "Tan# after intrathecal therapy!

7orticosteroi#s, an# especially #e amethasone ca&se #ehy#ration of brain tiss&e+that s why it is e5ecti'e in cerebral e#ema , an# this is sometimes interprete#

by ra#iolo%ists as U brain atrophy ! 3t is howe'er re'ersible an# lea'es no tracesafter the steroi# treatment has en#e#! /teroi#s are also responsible forpsycholo%ic alterations:#ist&rbances) #epression, (ts of an%er, sleeplessnessetcetera!

OTOTO;!C!T

This is partic&larly a problem after treatment with 7isplatin! The hi%her tones area5ecte# (rst! /ymptoms may increase o'er the years e'en if no more cisplatin is%i'en! 7ombination with ra#iotherapy on the brain an# especially on the innerear will increase the ris$ of ototo icity!

Therefore a&#iolo%ic chec$ is a#'ise# before start treatment with platincontainin% re%imens! The a&#io%rams sho&l# be repeate# j&st before e'eryco&rse of chemotherapy! 7hec$s after stop chemotherapy is also 'al&able, somepatients nee# hearin% ai#s later!

*V*(CU'*# "EC#O(!( O$ .O"E 5*V":

7orticosteroi#s, in combination with other #r&%s +"T is incriminate# are thec&lprit! This is partic&larly a problem for ol#er chil#ren +a few percent an# yo&n%a#&lts +&p to 20I ! "ost a5ecte#, or at least most c&mbersome, are the bi% joint

of the lower e tremities) hip an# $nee! 3f it occ&rs +pain, limitation of motion thebest #ia%nostic test, after physical e amination, is an "83 which will show atypical pattern! Plain 6rays may also show #ama%e in more a#'ance# cases!"eas&res to re#&ce the pain an# the possibility of permanent joint #ama%e arepre'entin% press&re on the a5ecte# joints, splints, b&t with passi'e motion+physiotherapy an# limitin% the steroi# e pos&re! .or instance by s$ippin% the#e a or pre#nsone p&lses in maintenance therapy an# %i'in% contin&o&s"T RK"P instea#!

Adapted from VUmc Authors Smits and Kors, 2008, revised 2011

Adapted for Indonesia by Veerman, Novemeber 201

Cheklist Malignancy Estella

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