onco management

7/23/2019 Onco Management

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PRINCIPLES OF ONCOLOGY ANDOUTLINE OF MANAGEMENT


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ONCOLOGY

The name itself comes to us thou!h Gee"an# Latin $o#s fo a ca%& fom the Gee"karkinosto the Latin cance& an# efes tothe cla$'li"e %loo# (essels e)ten#in! o(e

the suface of an a#(ance# %east cance*

Ru#olf +icho$ has the ce#it fo %ein! the,st to #emonstate that cance is a

#isease of cells an# that the #isease-o!esse# as a esult of a%nomal-olifeation*


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Causes of cance

Causes

Genetics

Mutationsof !enes

En(ionmental

To%acco

Alcohol

U+e)-osue

Ra#iation

Infections

O%esit.


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Genetics

Genes Tumours Syndrome

/RCA 01 /RCA 2 /east & o(a. & colon 3ee#ita. %easto(aian cance

APC Intestinal a#enomas &colon cance

FAP

/CL'0&/CL'2 Mantle cell l.m-homa

E4T 0&E4T 2 Follicula l.m-homa

3PC 0 Chon#osacoma

R/ 0 Retino%lastoma 3ee#ia.

etino%lastomaRET Me#ulla. ca th.oi# &

-heochomoc.tomaMen 2

MEN 0 Paath.oi#&-anceas&-ituata.

MEN 0

MET Pa-illa. enal tumou


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Essentials of cance!o$th


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Malignant transformation

Establish an autonomous lineageResist signals that inhibit growth

Acquire independence from signalsstimulating growth

Obtain immortality

Evade apoptosis

Acquire angiogenic competence

Acquire the ability to invade

Acquire the ability to disseminate and implant

Evade detectioneliminationGenomic instability

Subvert communication to and from theenvironmentmilieu


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Pinci-les of oncolo!.mana!ement

!" #re$referral mechanismsPatient e#ucation to eco!nise #an!es.m-toms an# si!ns

Self e)amination %. the -atient* e*!* %east& testis

E#ucation& !ui#ance an# -ost'efeal fee#%ac" fo famil.-actitiones in eco!nisin! #an!e s.m-toms an# si!ns an#eassuance*

A--o-iate efeal to s-ecialists hel-e# %. -ofomas containin!in#ications to efe sus-ecte# s"in& coloectal& %east& hea# an#nec" an# u--e !astointestinal cance

Rea#. a(aila%ilit. of eal. assessment an# #ia!nostic tests

%" #rimary diagnosis after referral'clinical assessment -lus

in(esti!ations& e*!* ima!in!& en#osco-.& %io-s.& ,ne nee#leas-iation c.tolo!.& la-aosco-.

&" Staging'a##itional in(esti!ation to seach fo e)tent of s-ea#5

Local s-ea#

L.m-h no#e s-ea# 3aemato!enous s-ea# 6%one& lun!& li(e& %ain7


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'" Multidisciplinary decision ma(ing'to fomulate the aims ofteatment an# to #eci#e the o-timum teatment5 Teatment -lannin!an# timin! of teatment& i#eall. %ase# on an#omise# contolle# tials6RCTs7 %ut also on e)-eience

Teatment ma. in(ol(e a sin!le entit.& o com%inations of su!e.&neoa#9u(ant o a#9u(ant chemothea-. an#8o a#iothea-.&-osto-eati(e chemo' o a#iothea-.& homonal thea-.

Patients shoul# %e entee# into clinical tials $hee %est teatment isnot esta%lishe#

)" The treatment

*" Repeat staging after operation or other treatment'$ith"no$le#!e of the o-eati(e ,n#in!s an# a e(ie$ of the histolo!.* Thisma. chan!e the -osto-eati(e -lan fo a#9u(ant thea-. an# -o(i#einfomation to calculate the statistical li"elihoo# of su(i(al8cue

+" #ost treatment surveillance'fo ecuence o a--eaance of ne$tumousin the ,el#*

," Auditof local outcomes to im-o(e :ualit. of cae* Patici-ation innational au#its


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Mana!ement

Sceenin!Dia!nose

Classif.

In(esti!ations

Sta!in! of cance

Teatment


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Sceenin!

Eal. #etection is the "e. to success in cance thea-.*

Sceenin! in(ol(es the #etection of #isease in anas.m-tomatic -o-ulation in o#e to im-o(e outcomes%. eal. #ia!nosis*

Sceenin! fo common cances usin! elati(el.nonin(asi(e tests is e)-ecte# to lea# to eal. #ia!nosis&allo$ moe conse(ati(e su!ical thea-ies $ith#ecease# mo%i#it.& an# -otentiall. im-o(e su!ical

cue ates an# o(eall su(i(al ates*

;e. factos that in


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Citeia fo sceenin!

The disease

> Reco!ni?a%le eal. sta!e

> Teatment at an eal. sta!e moe e=ecti(e than at a late sta!e

> Su@cientl. common to $aant sceenin!

The test

> Sensiti(e an# s-eci,c

> Acce-ta%le to the sceene# -o-ulation

> Safe

> Ine)-ensi(e

The programme

> A#e:uate #ia!nostic facilities fo those $ith a -ositi(e test

> 3i!h':ualit. teatment fo sceen'#etecte# #isease to minimise mo%i#it. an#motalit.

> Sceenin! e-eate# at inte(als if the #isease is of insi#ious onset

> /ene,t must out$ei!h -h.sical an# -s.cholo!ical ham


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Sceenin! use# in 5

Cance Sceenin! metho#s 5

/east Self e)amination & clinical e)amination &mammo!a-h.

Coloectal Fecal occult %loo# test 6FO/T7 o fecal

immunochemical test 6FIT7 & Dou%le'contast%aium enema 6DC/E7 & Fle)i%le si!moi#osco-.& colonosco-.

Postate Di!ital ectal e)amination 6DRE7 an# -ostate's-eci,c anti!en 6PSA7 test

Ce(i) Pa- test


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Dia!nosis

The #e,niti(e #ia!nosis of soli# tumos usuall. is o%taine#%. -efomin! a %io-s.of the lesion*

/io-s. ,n#in!s #etemine the tumo histolo!. an# !a#ean# thus assist in #e,niti(e thea-eutic -lannin!*

/io-s. s-ecimens of mucosal lesions usuall. ae o%taine#en#osco-icall. 6e*!*& (ia colonosco-e& %onchosco-e& oc.stosco-e7*

Lesions that ae easil. -al-a%le& such as those of the s"in&can eithe %e e)cise# o sam-le# %. -unch %io-s.*

Dee-'seate# lesions can %e locali?e# $ith com-ute#tomo!a-hic 6CT7 scan o ultasoun# !ui#ance fo %io-s.*


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O-en %io-sies ha(e the a#(anta!e of -o(i#in! moe tissue fo histolo!ice(aluationan# the #isa#(anta!e of %ein! an o-eati(e -oce#ue*

E)cisional %io-sies ae -efome# fo lesions fo $hich eithe coe %io-s.

is not -ossi%le o the esults ae non#ia!nostic*

E)cisional %io-sies shoul# %e -efome# $ith cuati(e intent& that is& %.o%tainin! a#e:uate tissue aoun# the lesion to ensue ne!ati(e su!icalma!ins*

Ma"in! of the oientation of the ma!ins %. sutues o cli-s %. thesu!eon an# in"in! of the s-ecimen ma!ins %. the -atholo!ist $ill allo$fo #etemination of the su!ical ma!ins an# $ill !ui#e su!ical e'e)cision if one o moe of the ma!ins ae -ositi(e fo micosco-ic tumoo ae close*

The %io-s. incision shoul# #iectl. o(elie the aea to %e emo(e# athethan tunnelin! fom anothe site& $hich uns the is" of contaminatin! ala!e ,el#*

Finall.& meticulous hemostasis #uin! a %io-s. is essential& %ecause ahematoma can lea# to contamination of the tissue -lanes an# can ma"esu%se:uent follo$'u- $ith -h.sical e)aminations much moe challen!in!*


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Classi,cation Di=eent tumous ae classi,e# in #i=eent $a.s

Most s:uamous e-ithelial tumous ae sim-l. classe# as $ell 6G07&mo#eate 6G27 o -ool. 6G7 #i=eentiate# *

A#enocacinomas ae also often classi,e# as G0& 2 o &

/ut -ostate cance is an e)ce-tion $ith $i#es-ea# use of the

Gleason s.stem* The Gleason s.stem !a#es -ostate canceacco#in! to the #e!ee of #i=eentiation of the t$o most -e(alentachitectual -attens*

The ,nal scoe is the sum of the t$o !a#es an# can (a. fom 2 60B 07 to 0 6 B 7& $ith the hi!he scoes in#icatin! -ooe-o!nosis*

The mana!ement of mali!nant l.m-homas is %ase# ,ml. u-onhisto-atholo!icalclassi,cation5 the ,st #istinction is %et$een3o#!"ins l.m-homa 63L7 an# the non'3o#!"ins l.m-homa 6N3L7*Each of these main t.-es of l.m-homa is then su%classi,e#acco#in! to a #i=eent scheme*

The ol# 3ealth O!ani?ation8Re(ise# Euo-eanAmeicanl.m-homa 63O8REAL7 s.stem classi,es 3o#!"ins l.m-homa into


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In(esti!ations

Ima!in! mo#alitiesMa"es


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Tumou ma"es

Po!nostic an# Pe#icti(e Tissue Ma"es

Tumo ma"es ae su%stances that can %e #etecte# inhi!he than nomal amounts in the seum& uine& otissues of -atients $ith cetain t.-es of cance*

Tumos ma"es ae -o#uce# eithe %. the cance cellsthemsel(es o %. the %o#. in a es-onse to the cance*

The temprognostic marker!eneall. is use# to #esci%e

molecula ma"es that -e#ict #isease'fee su(i(alisease's-eci,c su(i(al& an# o(eall su(i(al&

heeas the tempredictive markeroften is use# in theconte)t of -e#ictin! es-onse to cetain thea-ies*


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Seum ma"es

Postate s-eci,c anti!enCacinoem%.onic anti!en

Al-ha feto -otein

CA 0'

CA 2J'2


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PSA Postate's-eci,c anti!en 6PSA7 is -otentiall. the %est seum

ma"e no$ a(aila%le*

PSA is an an#o!en'e!ulate# seine -otease -o#uce# %. the-ostate e-ithelium*

PSA le(els ma. %e ele(ate# in the %loo# of men $ith %eni!n-ostate con#itions such as -ostatitis an# %eni!n -ostatich.-e-lasia& as $ell as in men $ith -ostate cance*

PSA le(els ha(e %een sho$n to %e useful in e(aluatin! thee=ecti(eness of -ostate cance teatment an# monitoin! foecuence afte thea-.*

In monitoin! fo ecuence& a ten# of inceasin! le(els isconsi#ee# moe si!ni,cant than a sin!le a%solute ele(ate#(alue*

A total seum PSA le(el of K n!8mL shoul# %e use# as atheshol# fo -efomin! a -ostate %io-s.


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CEA

Cacinoem%.onic anti!en 6CEA7 is a !l.co-otein foun# in theem%.onic en#o#emal e-ithelium*

Ele(ate# CEA le(els ha(e %een #etecte# in -atients $ith -ima.coloectal cance as $ell as in -atients $ith %east& lun!& o(aian&-ostate& li(e& an# -anceatic cance*

Le(els of CEA also ma. %e ele(ate# in %eni!n con#itions such as#i(eticulitis& -e-tic ulce #isease& %onchitis& li(e a%scess& an#alcoholic cihosis& es-eciall. in smo"es an# in el#el. -esons*

CEA measuement is most commonl. use# in the mana!ement of

coloectal cance*

CEA le(els ma. %e useful if o%taine# -eo-eati(el. an#-osto-eati(el. in -atients $ith a #ia!nosis of coloectal cance*Peo-eati(e ele(ation of CEA le(el is an in#icato of -oo -o!nosis*


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AFP Al-ha'feto-otein 6AFP7 is a !l.co-otein nomall. -o#uce# %. a

#e(elo-in! fetus* AFP le(els #ecease soon afte %ith in health. a#ults*

An ele(ate# le(el of AFP su!!ests the -esence of eithe -ima. li(ecance o a !em cell tumo of the o(a. o testicle* Rael.& othe t.-esof cance such as !astic cance ae associate# $ith an ele(ate# AFP

le(el*

/eni!n con#itions that can cause ele(ations of AFP inclu#e cihosis&he-atic necosis& acute he-atitis& chonic acti(e he-atitis& ata)ia'telan!iectasia& is"ott'Al#ich s.n#ome& an# -e!nanc.*

The sensiti(it. of an ele(ate# AFP le(el fo #etectin! 3CC isa--o)imatel. * AFP is consi#ee# to %e sensiti(e an# s-eci,cenou!h to %e use# fo sceenin! fo 3CC in hi!h'is" -o-ulations*

Cuent consensus ecommen#ations ae to sceen health. he-atitis /

(ius caies $ith annual o semiannual measuement of AFP le(el an#to sceen caies $ith cihosis o chonic he-atitis an# -atients $ith


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CA 0'

Cance anti!en 0' 6CA 0'7 is atumo'elate# anti!en that $as oi!inall.#e,ne# %. a monoclonal anti%o#.-o#uce# %. a h.%i#oma -e-ae# fom

muine s-leen cells immuni?e# $ith ahuman coloectal cance cell line*

The #ata ae insu@cient to ecommen#use of CA 0' fo sceenin!& #ia!nosis&su(eillance& o monitoin! of thea-. focolon cance*


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CA 0'

Cance anti!en 0' 6CA 0'7 is an e-ito-e of a la!emem%ane !l.co-otein enco#e# %. the MUC1!ene thattumo cells she# into the %loo#steam*

The CA 0' e-ito-e is eco!ni?e# %. t$o monoclonalanti%o#ies in a san#$ich a#ioimmunoassa.*

CA 0' le(els ae most useful in follo$in! the couse ofteatment in $omen #ia!nose# $ith a#(ance# %east cance*CA 0' le(els ae infe:uentl. ele(ate# in eal. %east cance*

CA 0' le(els can %e incease# in %eni!n con#itions such aschonic he-atitis& tu%eculosis& sacoi#osis& -el(icin


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CA 2J'2

The MUC'0 !ene -o#uct in the seum ma. %e:uantitate# %. usin! a#ioimmunoassa. $ith amonoclonal anti%o#. a!ainst the cance anti!en2J'2 6CA 2J'27*

CA 2J'2 le(els can %e ele(ate# in %east canceas $ell as in cances of the colon& stomach&"i#ne.& lun!& o(a.& -anceas& uteus& an# li(e*

Fist'timeste -e!nanc.& en#ometiosis& %eni!n%east #isease& "i#ne. #isease& an# li(e #iseasealso ma. %e associate# $ith ele(ate# CA 2J'2le(els*


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Ciculatin! Tumo Cells Ciculatin! tumo cells 6CTCs7 ae cells -esent in the %loo# that

-ossess anti!enic o !enetic chaacteistics of a s-eci,c tumot.-e*

One CTC #etection metho#olo!. is ca-tue an# :uantitation of CTCs$ith immunoma!netic %ea#s coate# $ith anti%o#. s-eci,c fo cell'suface& e-ithelial& o cance anti!ens*

Anothe metho#olo!. use# to #etect cance cells in the -ei-heal%loo# is RT'PCR* It has %een su!!este# that measuement of CTCscan %e an e=ecti(e tool fo selectin! -atients $ho ha(e a hi!h is"of ela-se an# fo monitoin! e@cac. of cance thea-.*

CTCs ha(e -o%a%l. %een most e)tensi(el. stu#ie# in %east cance*The most -omisin! #ata come fom the use of CTC measues inmetastatic %east cance*

The -o!nostic im-lications of #etection of CTCs %. RT'PCR ha(e%een intensi(el. stu#ie# fo melanoma*


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In the ecent multicente Sun%elt Melanoma Tial&

seial RT'PCR $as -efome# on -ei-heal %loo#sam-les usin! fou ma"est.osinase& melanomaanti!en eactin! to T cell 6MART'07& melanoma

anti!en 6MAGE7& an# !- 0to #etect occultmelanoma cells in the %loo#steam*

Althou!h thee $ee no #i=eences in su(i(al%et$een -atients in $hom at least one ma"e $as

#etecte# an# those in $hom no ma"es $ee#etecte#& the #isease'fee su(i(al an# #istant

#isease'fee su(i(al $ee $ose fo -atients in$hom moe than one ma"e $as #etecte# at an.

time #uin! follo$'u-*


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RT PCR


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/one Mao$ Micometastases Micometastatic #isease in the %one mao$& also efee# to as

minimal residual disease,also is %ein! in(esti!ate# as a -otential-o!nostic ma"e*

/one mao$ micometastatic #isease usuall. is #etecte# %.stainin! %one mao$ as-iates $ith monoclonal anti%o#ies toc.to"eatin& %ut othe metho#olo!ies such as


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Immunohistochemist.-ell typesite of

origin.

Site of origincell

type.

#rognosis and

treatment.E-ithelial 6cacinoma75c.to"eatins

Postate5 -ostate's-eci,c anti!en 6PSA7

/east cacinoma5ece-tos 6ER& PR& 3ER27

L.m-hoi# 6l.m-homa75CD& CD2

Lun!5 th.oi#tansci-tion facto'0

6TTF'07

En#ocine tumous5 ;iJ-olifeati(e in#e)

Melanoc.tic6melanoma75 S0

Th.oi#5 th.o!lo%ulin GIST5 CD00J

Neuoen#ocine5 CD&

chomo!anin

Coloectum5 c.to"eatin

2 6C;27Stomach&!.naecolo!ical&

+ascula5 CD0& CDK lun!5 c.to"eatin J 6C;J7

M.oi#5 #esmin& actin Li(e5 3e-Pa

O(a.5 CA02


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Othe Ai#s

ELECTRON MICROSCOPY 5 Electonmicosco-. allo$s tissue to %e (isualise# at(e. hi!h ma!ni,cation& e*!* 0 to * It ma. hel- to #eci#e the linea!e of

a non'neo-lastic o neo-lastic cell in #i@cultcases*

PCR

CYTOGENETICS AND FIS3 Immunohistochemist. an# FIS3 ae use# toassess 3ER2 am-li,cation in %east cance*


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Clinical a--lications of PCR totissue sam-les

Mutational anal.sis

Clonalit.

Loss of heteo?.!osit.

Chomosomal a%nomalities

Detection of mico'o!anisms


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Sta!in!

The Intenational Union a!ainstCance 6UICC7 is es-onsi%le fothe TNM 6tumou& no#es&

metastases7 sta!in! s.stem focance*

This s.stem is com-ati%le $ith&

an# elates to& the AmeicanCance Societ. 6AQCC7 s.stem fosta!e !ou-in! of cance*


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Teatment

Su!icalMe#ical

Ra#iation


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Su!ical Mana!ement of Pima.Tumos

The !oal of su!ical thea-. fo cance is toachie(e oncolo!ic cue*

A cuati(e o-eation -esu--oses that the

tumo is con,ne# to the o!an of oi!in o tothe o!an an# the e!ional l.m-h no#e%asin*

The o-ea%ilit. of -ima. tumos is %est#etemine# %efoe su!e. $ith a--o-iateima!in! stu#ies that can #e,ne the e)tentof local'e!ional #isease*


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The unifom !oal fo all successful oncolo!ico-eations seems to %e achie(in! $i#el. ne!ati(ema!ins $ith no e(i#ence of macosco-ic o

micosco-ic tumo at the su!ical ma!ins*

The im-otance of ne!ati(e su!ical ma!ins fo localtumo contol an#8o su(i(al has %een #ocumente# foman. tumo t.-es& inclu#in! sacoma& %east cance&

-anceatic cance& an# ectal cance*

Thus it is clea that e(e. e=ot shoul# %e ma#e toachie(e micosco-icall. ne!ati(e su!ical ma!ins*

In"in! of the ma!ins& oientation of the s-ecimen %.the su!eon& an# imme#iate !oss e(aluation of thema!ins %. a -atholo!ist usin! fo?en'section anal.sis$hen necessa. ma. assist in achie(in! ne!ati(ema!ins at the ,st o-eation*


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In the -ast it $as -esume# that the moea#ical the su!e.& the %ette theoncolo!ic outcome $oul# %e*

O(e the -ast 2 .eas& this has %een

eco!ni?e# as not necessail. %ein! tue&$hich has le# to moe conse(ati(eo-eations& $ith $i#e local e)cisionse-lacin! com-atmental esections of

sacomas& an# -atial mastectomies& s"in's-ain! mastectomies& an# %east'conse(in! thea-ies e-lacin! a#icalmastectomies fo %east cance*


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Unesecta%le cases ae

Patients in $hom the -ima.tumo is not esecta%le $ithne!ati(e su!ical ma!insae

consi#ee# to ha(e ino-ea%le#isease*

Disease in(ol(in! multi-le #istantmetastasesis #eeme# ino-ea%le%ecause it is usuall. not cua%le

$ith su!e. of the -ima.


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Su!ical Mana!ement of theRe!ional L.m-h No#e /asin

Most neo-lasms ha(e the a%ilit. to metastasi?e (ia thel.m-hatics*

Theefoe& most oncolo!ic o-eations ha(e %een #esi!ne#to emo(e the -ima. tumo an# #ainin! l.m-hatics en

%loc*

This t.-e of o-eati(e a--oach usuall. is un#eta"en$hen the l.m-h no#es #ainin! the -ima. tumo site liea#9acent to the tumo %e#& as is the case fo coloectal

cances an# !astic cances*

Fo tumos in $hich the e!ional l.m-h no#e %asin is notimme#iatel. a#9acent to the tumo 6e*!*& melanomas7&l.m-h no#e su!e. can %e -efome# thou!h a se-aate

incision*


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Fo most cances& in(ol(ement of thel.m-h no#es is one of the mostsi!ni,cant -o!nostic factos*

Inteestin!l.& emo(al of a la!enum%e of l.m-h no#es has %een foun#

to %e associate# $ith an im-o(e#o(eall su(ial ate fo man. tumos&inclu#in! %east cance& colon cance&an# lun! cance*

L.m-ha#enectom. is im-otant fosta!in! an# su(i(al*


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ill Ro!es e=ect

This -henomenon is& i#enti,cation of metastasesthat ha# fomel. %een silent an# uni#enti,e#lea#s to sta!e mi!ation an# thus to a -ecei(e#im-o(ement in chances of su(i(al*

Cleal. the im-act of l.m-ha#enectom. onsu(i(al $ill not %e easil. esol(e#*

/ecause minimi?in! e!ional ecuences as

much as -ossi%le is a !oal of cance teatment&the stan#a# of cae emains l.m-ha#enectom.fo most tumos*

h i i


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L.m-hatic ma--in!technolo!.A elati(el. ne$ #e(elo-ment in the su!ical

mana!ement of the clinicall. ne!ati(e e!ionall.m-h no#e %asin is the into#uction of l.m-haticma--in! technolo!.*

L.m-hatic ma--in! an# sentinel l.m-h no#e %io-s.$ee ,st e-ote# in 0JJ %. Ca%anas fo -enilecance*

No$& sentinel no#e %io-s. is the stan#a# of cae fothe mana!ement of melanoma an# %east cance*

Moeo(e& the utilit. of sentinel no#e %io-s. in othecance t.-es is %ein! e)-loe#*


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The ,st no#e to ecei(e #aina!e fom the tumo site is teme# thesentinel no#e*

This no#e is the no#e most li"el. to contain metastases& ifmetastases to that e!ional l.m-h no#e %asin ae -esent*

The !oal of l.m-hatic ma--in! an# sentinel l.m-h no#e %io-s. is toi#entif. an# emo(e the l.m-h no#e most li"el. to containmetastases in the least in(asi(e fashion*

The -actice of sentinel l.m-h no#e %io-s. follo$e# %. selecti(ee!ional l.m-h no#e #issection fo -atients $ith a -ositi(e sentinell.m-h no#e a(oi#s the mo%i#it. of l.m-h no#e #issections in-atients $ith ne!ati(e no#es*

An a##itional a#(anta!e of the sentinel l.m-h no#e techni:ue is thatit #iects attention to a sin!le no#e& $hich allo$s moe caefulanal.sis of the l.m-h no#e most li"el. to ha(e a -ositi(e .iel# an#inceases the accuac. of no#al sta!in!*


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Poce#ue

L.m-hatic ma--in! is -efome# %. usin! isosulfan%lue #.e& technetium'la%ele# sulfu colloi# oal%umin& o a com%ination of %oth techni:ues to#etect sentinel no#es*

The com%ination of %lue #.e an# technetium has%een e-ote# to im-o(e the ca-a%ilit. of #etectin!sentinel l.m-h no#es*

The no#al #aina!e -atten usuall. is #etemine#$ith a -eo-eati(e l.m-hoscinti!am& an# the hotan#8o %lue no#es ae i#enti,e# $ith the assistanceof a !amma -o%e an# caeful no#al %asine)-loation*


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The no#es ae e(aluate# $ith seialsectionin!& hemato).lin an# eosin stainin!&

an# immunohistochemical anal.sis $ith S'0 -otein an# homato-inemeth.l%omi#e stainin! fo melanoma an#c.to"eatin stainin! fo %east cance*

Stu#ies also ae on!oin! to e(aluate theuse of molecula techni:ues such as RT'PCR to a-i#l. assess the sentinel no#e

status in the intao-eati(e settin!*


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S i l M t f


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Su!ical Mana!ement ofDistant Metastases

Patient selection is the "e. to the success of su!icalthea-. fo #istant metastases*

The cance t.-e is a ma9o #eteminant in su!ical

#ecision ma"in!*

A li(e metastasis fom a colon cance is moe li"el.to %e an isolate# an# thus esecta%le lesion than ali(e metastasis fom a -anceatic cacinoma*

In cuati(e su!e. fo #istant metastases& as $ithsu!e. fo -ima. tumos& the !oal is to esect themetastases $ith ne!ati(e ma!ins


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Chemothea-.In -atients $ith #ocumente# #istant metastatic #isease&

chemothea-. is usuall. the -ima. mo#alit. of thea-.*

The !oal of thea-. in this settin! is to #ecease the tumo%u#en& thus -olon!in! su(i(al*

Chemothea-. a#ministee# to a -atient $ho is at hi!h is" fo#istant ecuence %ut has no e(i#ence of #istant #isease isefee# to as adjuvant chemotherapy.

The !oal of a#9u(ant chemothea-. is ea#ication of micometastatic #isease& $ith the intent of #eceasin! ela-se ates

an# im-o(in! su(i(al ates*

A#9u(ant thea-. can %e a#ministee# afte su!e.6-osto-eati(e chemothea-.7 o %efoe su!e. 6-eo-eati(echemothea-.& neoa#9u(ant chemothea-.& o in#uctionthea-.7*

P ti


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Pe o-eati(echemothea-.

Peo-eati(e chemothea-. has thee -otential a#(anta!es*

The ,st is that -eo-eati(e e!ession of tumo canfacilitate esection of tumos that $ee initiall. ino-ea%leo allo$ moe conse(ati(e su!e. fo -atients $hosecance $as o-ea%le to %e!in $ith*

The secon# a#(anta!e of -eo-eati(e chemothea-. is theteatment of micometastases $ithout the #ela. of-osto-eati(e eco(e.*

The thi# a#(anta!e is the a%ilit. to assess a canceses-onse to teatment clinicall.&afte a num%e of cousesof chemothea-.& an# -atholo!icall.& afte su!icalesection* This is es-eciall. im-otant if altenati(eteatment e!imens ae a(aila%le to %e o=ee# to -atients$hose #isease es-on#e# ina#e:uatel.*

Tumou sensiti(it. to c.toto)ic


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. .chemothea-.

/ighly sensitivetumours$reasonable

prospect of cure

Moderatelysensitive tumours$palliation is the

main ob0ective

Relatively insensitivetumours$cytoto1ictherapy only indicated

in specialcircumstances or withtechniques of regionalinfusion

3o#!"ins #isease /east cance Cacinoma of lun! othe

than small'cell t.-e3i!h'!a#el.m-homas

Lo$'!a#el.m-homas

cacinomas of the hea#an# nec"

Testicula tumous Multi-le m.eloma Cacinoma of uteus an#ce(i)

Choiocacinoma Small'cell 6oat'cell7cacinoma of lun!

3e-atocellula cacinoma

ilms tumou Coloectal cance Renal a#enocacinoma

To)ic e=ects of


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To)ic e=ects ofchemothea-./one mao$ su--ession5 Causes anaemia&

thom%oc.to-enia an# leuco-enia 6-otentiall. fatal7

Immunosu--ession5Causes #iminishe# esistance too--otunistic infections

Nausea an# (omitin!5 Ten# to occu $ithin an hou ot$o of chemothea-.

Disu-tion of !astointestinal e-ithelial tuno(e5Causes #iahoea an# oal ulceation

To)icit. to hai follicles5 Paticulal. eto-osi#e&c.clo-hos-hami#e an# #o)ou%icin*Causes hai loss

Gona#al in9u.5 Loss of li%i#o& steilit. an# -ossi%le

muta!enesisRa-i# tumou #estuction on a massi(e scale5 Lea#s

to elease of -uines an# -.imi#ines 6onl. a -o%lemin leu"aemias an# l.m-homas7 $hich causeh.-euicaemia& -esentin! as o%stucti(e uo-ath.

an# enal failue*


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3omonal Thea-.

Some tumos& most nota%l. %east an# -ostate cances&oi!inate fom tissues $hose !o$th is un#e homonal contol*

3omonal anticance a!ents inclu#e an#o!ens& antian#o!ens&antiesto!ens& esto!ens& !lucocoticoi#s& !ona#oto-ininhi%itos& -o!estins& aomatase inhi%itos& an# somatostatin

analo!ues*

3omones o homone'li"e a!ents can %e a#ministee# to inhi%ittumo !o$th %. %loc"in! o anta!oni?in! the natuall. occuin!su%stance& such as $ith the esto!en anta!onist tamo)ifen*

3omonal thea-. -o(i#es a hi!hl. tumo's-eci,c fom ofthea-. in sensiti(e tissues*

In %east cance& esto!en an# -o!esteone ece-to status isuse# to -e#ict the success of homonal thea-.*


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Ta!ete# thea-.

The %asic -inci-le of molecula thea-eutics is to e)-loitthe molecula #i=eences %et$een nomal cells an# cancecells to #e(elo- ta!ete# thea-ies*

Thus ta!ete# thea-ies usuall. ae #iecte# at the-ocesses in(ol(e# in tumo !o$th athe than #iectl.ta!etin! the tumo cells*

The i#eal molecula ta!et $oul# %e e)clusi(el. e)-esse#in the cance cells& %e the #i(in! foce of the -olifeationof the cance cells& an# %e citical to thei su(i(al*

The ma9o !ou-s of ta!ete# thea-. a!ents ae inhi%itosof !o$th facto ece-tos& inhi%itos of intacellula si!naltans#uction& cell'c.cle inhi%itos& a-o-tosis'%ase#thea-ies& an# antian!io!enic com-oun#s*


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Ta!ete# Thea-ies

Generic 2ame Target 3nitial 3ndication

Tastu?uma% 3e 2 /east cance

La-atini% 3e 2 1 EGFR /east cance

Cetu)ima% EGFR Coloectal cance

/e(aci?uma% +EGF Coloectal cance

Soafeni% +EGFR&PDGFR Renal cellcacinoma

Temsiolimus mTOR Renal cellcacinoma

Imatini% C'"it & %c'a%l &PDGFR

GIST 1 CML

Sunitini% C'"it & PDGFR &+EGFR

CML


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Immunothea-.

The aim of immunothea-. is to in#uce o -otentiateinheent antitumo immunit. that can #esto.cance cells*

Cental to the -ocess of antitumo immunit. is the

a%ilit. of the immune s.stem to eco!ni?e tumo'associate# anti!ens -esent on human cances an#to #iect c.toto)ic es-onses thou!h humoal o T'cellme#iate# immunit.*

O(eall&T'cellme#iate# immunit. a--eas to ha(ethe !eate -otential of the t$o fo ea#icatin!tumo cells* T cells eco!ni?e anti!ens on thesufaces of ta!et cells as small -e-ti#es -esente#%. class I an# class II M3C molecules*


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Tumou (accines

The eal. attem-ts at (accination a!ainst cances use#allo!eneic cultue# cance cells& inclu#in! ia#iate#cells& cell l.sates& an# she# anti!ens isolate# fom tissuecultue su-enatants*

An altenate state!. is the use of autolo!ous tumo(accines*

Tissue s-eci,cit. an# immuno!enicit. ae im-otant#eteminants in choosin! an a--o-iate ta!et*

+accines #iecte# at #e,ne# tumo anti!ens aim tocom%ine selecte# tumo anti!ens an# a--o-iate outesfo #eli(ein! these anti!ens to the immune s.stem too-timi?e antitumo immunit.*


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Limitations

Toleanceto self'anti!ens e)-esse# in tumosis a limitation in !eneatin! antitumoes-onses*

Recentl.& se(eal -ath$a.s that mo#ulatetoleance an# a--oaches to mani-ulatin!these -ath$a.s ha(e %een i#enti,e#5

-ath$a.s that acti(ate -ofessional anti!en'-esentin! cells such as Toll'li"e ece-tos&

!o$th factos& an# the CDK -ath$a.Hc.to"ines to enhance immunoacti(ationH an#-ath$a.s that inhi%it T'cell inhi%ito. si!nals o

Te!s*


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A#(ancements *

A ne$ state!. %ein! acti(el. e)-loe# in(ol(es the useof c.toto)ic T'l.m-hoc.te anti!en K 6CTLA'K7*

CTLA'K e)ists on the sufaces of T cells an# has ahomeostatic immunosu--essi(e function&

#o$ne!ulatin! the es-onse of T cells to stimuli*

T$o full. human monoclonal anti'CTLA'K anti%o#ies&i-ilimuma% an# temelimuma%& ae in clinical#e(elo-ment*

Anti'CTLA'K anti%o#ies ae un#e stu#. fo use inmelanoma as $ell as se(eal othe cance t.-es assin!le a!ents& in com%ination $ith inteleu"in'2&chemothea-.& o -e-ti#e (accines*


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One of the -omisin! a--oaches to incease thenum%e of tumo cells tans#uce# is the use of a

e-lication'com-etent (iussuch as a -a(o(ius&human eo(ius& o (esicula stomatitis (ius thatselecti(el. e-licates $ithin mali!nant cells an#l.ses them moe e@cientl. than it #oes nomal cells*

Anothe state!. fo "illin! tumo cells $ith suici#e!enes e)-loits tumo's-eci,c e)-ession elements&such as the MUC'0& PSA& CEA& o +EGF -omotes&that can %e use# to achie(e tissue's-eci,c o tumo's-eci,c e)-ession of the #esie# !ene*

/ecause the !oal in cance thea-. is to ea#icates.stemic #isease& o-timi?ation of #eli(e. s.stems isthe "e. to success fo !ene thea-. state!ies*


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Ra#iothea-.

A%so-tion of a#iation %. the ta!ettissue causes hi!hl. eacti(e feea#icals to a--ea $hich #ama!eDNA an# cause cell #eath at mitosis*

ith thei hi!h ate of -olifeation&cance cells ae -aticulal. sensiti(e&

%ut nomal tissues $ith a hi!h ate ofcell tuno(e 6e*!* !ut mucosa an#%one mao$7 ae also (ulnea%le*

Ra#iation can %e #iecte# to a


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Ra#iation can %e #iecte# to atumou in thee $a.s5

E1ternal beam irradiation'this is the metho# mostcommonl. em-lo.e# fo s"in lesions an# #ee-l. locate#tumous

4ocal application of radioisotopes 5brachytherapy6' thisin(ol(es -lacin! the a#iation souce u-on o $ithin the tissue

to %e ia#iate#*#laquesouces of a#iation can %e em-lo.e# fo s"in

mali!nancies

Ra#ioacti(e iridium wires or caesium needlescan %eim-lante# in the oal ca(it.& -ostate& s"in an# sometimes%east& !i(in! hi!h'#ose local ia#iation*

Im-lantation is usuall. -efome# un#e !eneal anaesthesia*

Fo cance of the uteus an# ce(i)& the a#ioacti(e souce is-lace# in a seale# containe $ithin the uteine o (a!inalca(it.H it can %e insete# $ithout is" to sta= (ia a


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#metho# 5

Systemic radioisotope therapy'a#ioacti(eio#ine !i(en %. mouth o inta(enousl. is a$ell'esta%lishe# teatment fo th.oto)icosisan# can also %e use# fo teatin! $ell'#i=eentiate# th.oi# tumous -o(i#e# theest of the th.oi# has %een emo(e#& e(en ife)tensi(e metastases ae -esent*

Attem-ts ae still %ein! ma#e to #iect

a#ioisoto-es -ecisel. to cance cells %.attachin! them to tumou's-eci,c monoclonal

anti%o#ies*

Ra#iosensiti(e o esistant


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Ra#iosensiti(e o esistant

3i!hl. a#iosensiti(e

Ma9o a--lications of


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Ma9o a--lications ofa#iothea-.

Ra#iothea-. has thee ma9oa--lications in cance teatment5

as a -ima. cue&

as a#9u(ant teatment to su!e.6an#8o chemothea-.7 o

as -alliation*

Pima. cuati(e


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.a#iothea-.Ra#iothea-. $ith cuati(e intent is "no$n as radicalradiotherapy& an# is $i#el. use# fo %asal cell an#

s:uamous cell cacinomas of the s"in*

It is also use# fo cetain tumous $hich ae technicall.#i@cult to emo(e o $hee su!e. $oul# %e -aticulal.mutilatin!& as in the hea#& nec" an# la.n)*

Ra#iothea-. can %e #iecte# at the -ima. lesion an#e!ional l.m-h no#es if a--o-iate an# ates of cue aecom-aa%le to those achie(e# %. su!ical e)cision*

Ra#iothea-. is em-lo.e# in the teatment of most

common soli# tumous an# in eal. cases of 3o#!"in an#non'3o#!"in l.m-homas*

Ra#iothea-. can also achie(e cue in u- to of %la##ecances& $ith sal(a!e c.stectom. ese(e# fo ecuence*


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A#9u(ant a#iothea-.The -inci-le un#el.in! ad0uvant therapy& $hethe a#iolo!ical& chemical o

homonal& is that clinicall. un#etecta%le micometastases ae often -esent intissue suoun#in! a -ima. lesion& in e!ional no#es an# in emote locations*

These ae %elie(e# to %e es-onsi%le fo local& e!ional an# s.stemic ecuenceafte a -ima. lesion has a--aentl. %een com-letel. emo(e#*

A#9u(ant a#iothea-. can %e a--lie# to local tissue an# e!ional no#es %efoesu!e. 6"no$n as neoad0uvant therapy7& afte su!e. o %oth& to t. toeliminate micometastases*

A#9u(ant a#iothea-. is $i#el. em-lo.e# fo cance of the %east afteemo(in! the -ima. lesion locall. o %. mastectom.* If a)illa. no#es aein(ol(e#& a#iothea-. can %e an altenati(e to a#ical l.m-h no#e cleaance*

Ra#iothea-. is also hi!hl. e=ecti(e a#9u(ant thea-. in seminoma of the testis*

In cetain cances& teatment a shot time %efoe su!e. $ith eithea#iothea-. o chemothea-. o %oth can %in! %ene,ts* This ma. enhance thecue ate fo su!e. o it ma. %e use# to #o$nsi?e a cance to ma"e su!e.-actica%le& e*!* in locall. a#(ance# ectal cance*


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Palliati(e a#iothea-.

Palliati(e a#iothea-. is em-lo.e# fo local contol of -ima. ometastatic lesions $ith the intention of teatin! s.m-toms an#causin! the minimum of si#e e=ects*

It is also em-lo.e# to -e(ent im-en#in! com-lications& e*!* s-inalco# com-ession*

Much lo$e total #oses ae use# fo -alliation than fo attem-ts atcueH shot couses o single high$dose fractionsae usuall.a#e:uate an# ae tolea%le an# con(enient fo the -atient*

Ra#iothea-. is -aticulal. e=ecti(e in contollin! metastatic

#e-osits in %one an# %ain*

The -ain of %one metastases can often %e com-letel. elie(e# %.a#iothea-.& as can some of the neuolo!ical manifestations of%ain secon#aies*


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Com-lications of RT

Systemic side e7ectsMalaise an# fati!ue'(e.common

E7ects occurring in irradiated tissues

S"in 6es-eciall. a)illa& !oin an# -eineum7 5 Re#ness&itchin! an# mil# -ain* S"in %ea"#o$n

A%#omen an# -el(is 5 Nausea& (omitin!& #iahoeaFe:uenc.& #.suia& haematuia 6a#iation c.stitis7

D. mouth 6)eostomia7 #ue to sali(a. !lan# in9u.

Painful mouth& #.s-ha!ia an# altee# taste* This is #ueto in


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Ra#iation in#uce# cances

Types of e1posure Type of cancerNec" ia#ition #uin! chilhoo# Th.oi# cacinoma

Ra#iation thea-. fo othemali!nant tumous

Th.oi#&%east&!astic&lun!cances*Melanoma

Canial ia#iation CNS tumous/east ia#iation fo -ost-atum mastitis

/east cances

/ush lic"in! %. a#ium #ial-aintes

/one sacomas

Uanium e)-osue Lun! cancesInuteo e)-osue leu"emia

Pe(ention An ounce of -e(ention


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Pe(ention ' An ounce of -e(entionis $oth a -oun# of cue

Cance -e(ention can %e #i(i#e# intothee cate!oies5

6a7 -ima. -e(ention 6i*e*& -e(ention

of initial cances in health. in#i(i#uals7&6%7 secon#a. -e(ention 6i*e*&

-e(ention of cance in in#i(i#uals $ith-emali!nant con#itions7& an#

6c7 tetia. -e(ention 6i*e*& -e(entionof secon# -ima. cances in -atientscue# of thei initial #isease7*


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chemo-e(ention

The s.stemic o local a#ministation of thea-eutica!ents to -e(ent the #e(elo-ment of cance& calle#chemo-e(ention*

E) 0 5 tamo)ifen a#ministation e#uces the is" of

%east cance %. one half an# e#uces the is" ofesto!en ece-to-ositi(e tumos %. in hi!h'is" -atients*

E) 2 5 Celeco)i% has %een sho$n to e#uce -ol.-num%e an# -ol.- %u#en in -atients $ith familial

a#enomatous -ol.-osis 6FAP7E) 5 In hea# an# nec" cance& 0'cis'etinoic aci#

has %een sho$n %oth to e(ese oal leu"o-la"ia an#to e#uce secon# -ima. tumo #e(elo-ment*


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Recent

a#(ance

s

Ten#s an# E(ol(in! Technolo!ies


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in Oncolo!. ' Cance Sceenin! an#Dia!nosis

Mati)'assiste# lase #eso-tionioni?ation time'of'


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Ten#s an# E(ol(in! Technolo!ies inOncolo!. su!ical thea-.

The cuent ten# in su!e. is to$a# moeconse(ati(e esections*

ith ealie i#enti,cation of tumos& moeconse(ati(e su!eies ma. %e -ossi%le* The

!oal& ho$e(e& is al$a.s to emo(e the tumo en%loc $ith $i#e ne!ati(e ma!ins*

Anothe inteestin! aea %ein! e)-loe# is the

#estuction of tumos %. techni:ues such asa#iofe:uenc. a%lation& c.oa%lation& an# heat'-o#ucin! technolo!ies li"e lases& mico$a(es&o focuse# ultasoun#*


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T3AN; YOU

##i i i #


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A##itions e:uie#

Nanotechnolo!.Ro%otics

In su!ical oncolo!.

onco management

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