Women trombosis and Cancer

8/19/2019 Women trombosis and Cancer

http://slidepdf.com/reader/full/women-trombosis-and-cancer 1/106

A Global Continuing Education Train the Trainer



Objectives of this TTT Session

• Provide international opinion leaders with a brief overview of

the WTC initiative, established needs, program reach,

educational measurements and expected outcomes globally

• Review accredited content and its multiple touch points

o Practice assessment tool

o Overview data summary

o Case series only ! case will be presented on Web"x#

• Present accreditation criteria for "$%&'"(CC%" online# and

Royal College of Physicians and &urgeons live and online#

• )iscuss roles and responsibilities for logistical support

• (nswer any *uestions to help you teach the program in your

region



WebEx Moderator, Facilitators and Timing

• +ntroduction of international moderator expert

• ogistical support team

• &lides !-./ ogistical support facilitator# 0 !/ minutes

• &lides .!-12 "xpert# 0 *uic3 review 0 4/ minutes

• ! case presentation 0 !5 minutes

• Conclusions and next steps 0 5 minutes



International Steering Committee

Co-Chairs

• Pr6 )omini*ue 7arge-8ancel 7rance#

• Pr6 9enri 8ounameaux &wit:erland#

Steering Committee• Pr6 Rupert 8auersachs ;ermany#

• Pr6 8en<amin 8renner +srael#

• )r6 Philippe )ebourdeau 7rance#

• Pr6 =ames )ou3etis Canada#

• Pr6 %anuel %onr>al &pain#

• Pr6 +ngrid Pabinger (ustria#

Consltant

• Rt6 9on6 Pr6 ord (<ay ?a33ar



S!onsoring Organi"ations and #eer $evie%

• This program was sponsored with an unrestricted

educational grant from (spen Pharmacare

• The program content has been reviewed by an

international steering committee of experts

• The content has been peer reviewed by accredited

providers to ensure ethical balance and clinical

relevance



• &ubmitted program for online accreditation with the "uropean $nion of

%edical &pecialists'"(CC%"

• &ubmitted for live and online accreditation with the Royal College of

Physicians and &urgeons of Canada via approved accredited provider

%c;ill $niversity#

• (ll spea3ers to complete Conflict of +nterest and )isclosures with

provided templates

• Total credits re*uested@ !2 credits

o !65 credits@ Pre-C%" practice assessments nA4#o !6/ credit@ Overview

o !/ credits@ Cases ! credit'case#

o !65 credits@ !-month-post-C%" practice assessments nA4#

o !65 credits@ 4-month-post-C%" practice assessments nA4#

o

/65 credit@ &elf-reflective conclusion on impact of clinical practice

&ccredited #roviders Embargoed ntil

&!!roved



The Edcational Continm

• 7ive touch points over B-5 months

• Combination of online and live• %etrics gathering using practice assessments 4'participant x 4#

• +nteractivity with peers to validate 3nowledge transfer,

reinforcement and self-reflective practice assessment

PracticeAssessm

entsPre-CME

1-4 weeksprior

Lie!"nli

ne CME

PracticeAssessm

entsPost-CME1 month

post

PracticeAssessm

ents

Post-CME# months

post

$el%-&e'ectieE(ercise

Practice)mproemen

t



#ractice &ssessment

• Will be completed by each participanto Preferably 4 assessments per touch point as previously seen#

• (ll assessments, as well as online C%" completion,

newsletters, updates'3ey pearls will beexecuted'distributed via the %%%'WTCCME'com

website

• (ll data will be anonymous and approved as an

accredited C%" intervention

http://www.wtccme.com/

http://www.wtccme.com/



#ractice assessment ( )accredited for ! to ('* credits+

• Physicians will enter data from at least ! female patient with a diagnosis of cancer and T"6

Physicians can complete up to 4 patient practice assessments - to be ta3en (- %ees before

attending a C9" activity6

#ractice assessment . )accredited for ! to ('* credits+• One month following completion of the C%" activity, physicians will enter data from at least ! more

female patient with a diagnosis of cancer and T"6 Physicians can complete up to 4 patient

practice assessments to be ta3en ( month after having attended the C9" activity6

#ractice assessment / )accredited for ! to ('* credits+

• Three month following completion of the C%" activity, physicians will enter data from at least !

more female patient with a diagnosis of cancer and T"6 Physicians can complete up to 4 patientpractice assessments to be ta3en / months after having attended the C9" activity6

0ata collected %ill evalate an1 change in behavior of a!!ro!riate

treatment and !erio!erative !ro!h1laxis of 2TE in %omen %ith cancer

#ractice &ssessment )cont3d+



#rogram Content

• 7ocused on Women, Thrombosis and Cancer

• +ncludes pre-tests, post-tests, cases, interactive

*uestions, practice assessments

• 7inal accredited self-reflective conclusion for clinical

impact

• Program is very flexibleo Practice assessments

o Overview as a stand alone#

o Cases teaching ! case or several#

o Combination of any of the above 0 accredited separately



Table of Contents4Case Stdies

*TE in $urgicalCancer+ CericalCancer Patient

1

*TE in $urgicalCancer+ Endometrial

Cancer Patient,

*TE in $urgicalCancer+ Colorectal

Cancer Patient#

*TE in MedicalCancer+ Adanced

reast Cancer.


Lung Cancer/

*TE in MedicalCancer+ AdancedPancreatic Cancer

0

Catheter-&elated

Thrombosis+ Earlreast Cancer Patient4

Catheter-&elatedThrombosis+ "arian

Cancer Patient2

*TE in Pregnanc+Throid Cancer

Patient3*TE in Pregnanc+Melanoma Cancer

Patient1

"eriew

The international *TE and cancer guidelines mobile

app ma be used as a decision tool when reiewingthe case studies 5%ree %or download6 T", venous thromboembolism6



#rogram 5lobal $each )T6C+

• (lgeria

• (rgentina

• 8ra:il

• Canada

• Colombia

• 7rance

• ;ermany

• 9ungary

• +ndonesia

• +taly

• ?a:a3hstan

• ?orea

• %alaysia

• %exico

• %orocco



Ex!ected Otcomes

• )ata analysis based on collected practice assessments and potentially

through self-reflective exercises

• ;reater upta3e of mobile application of +nternational guidelines T"

and cancer

• ?nowledge transfer comparisons across countries and healthcareprovider types versus global findings

• )ata utili:ation@ Creation of new cases based on identified real world

gaps and for needs assessments for future accreditations

• Publication of new Women, Thrombosis and Cancer guidance in

indexed <ournal

• "vidence to demonstrate a positive outcome on clinical practice and

on women who present with specific cancers and thrombosis ris3s

• Presentations as symposia, abstracts and poster sessions in various

countries and congresses



The Edcational 7eed



&ddressing an 8nmet Medical 7eed

7omen 8 Cancer

Breast cancer is the 2nd most importaCancer is increasing faster in Women

XXIst century of Women

Cancer 8 Thrombosis

VTE is the second-leading causeof death in patients with cancer

4 to 2! of patients withcancer ha"e at least one VTE

e"ent

9

:7omen Thrombosis

Cancer pro;ect



Identif1ing 5a!s in Medical #ractice

• iterature reviews

• ;uidelines for Thrombosis and Cancer were identified

and included in content

• ;roup discussions with co-chairs and international

steering committee

• Review of previous program feedbac3 from congresses

• aunched with a symposium at the 2th +nternational

&ymposium on WomenEs 9ealth +ssues in Thrombosis

and 9aemostatis W9+T9# in 8erlin ./!56 )ata

collected from international participants6



O!ening $emars

Pr. Dominique Farge-Bancel, France

M1elo!roliferative 0isorders in Women

Dr. Martin Ellis, Israel

Thrombosis and Cancer in S!ecial Female #o!lations

Pr. Benjamin Brenner, Israel

Central 2enos Catheters and Thrombosis in #atients %ith 6reast Cancer

Dr. Philippe Debourdeau, France

S!ecific 5idelines for Cancer-&ssociated Thrombosis in Women9Moderator: Pr. Benjamin Brenner, Israel

Debaters: Pr. Dominique Farge-Bancel, France

Pr. upert Bauersachs, !erman"

Conclding $emars

Pr. Benjamin Brenner, Israel

:anch S1m!osim - .;(*



)n which o% the %ollowing patients would oumost likel recommend *TE prophla(is<

Sam!le #olling $eslts< =estion (



7hat do ou think would improe theoutcomes o% women with cancer at risk o%

*TE<

Sam!le #olling $eslts< =estion >



$oles and $es!onsibilities

• &pea3ers to prepare disclosure forms and present these at each C%"

program

• &pea3ers to discuss which components to be presented with (spen field

team overview, casesF Which onesF#

• &pea3ers to reinforce the need to complete the post ! month, post 4

month and reflective exercise with all participants

• (spen field team responsible for local'country logistics, invitations using

accreditor approved invitations, provide all handouts, gather evaluations

and sign in sheet

• (spen field team to send all gathered evaluations, sign in sheets and

disclosure forms to C%" &olutions for auditing

• C%" &olutions to manage microsite for all participants to complete the

pre, post and 4 month post practice assessments, tabulate data, wor3

with statistician to draft data reports for future publications, abstracts,

posters and guidance document publication



Webex !resentation< overvie% and ( case

*TE in $urgicalCancer+ CericalCancer Patient

1

*TE in $urgicalCancer+ Endometrial

Cancer Patient,

*TE in $urgicalCancer+ Colorectal

Cancer Patient#


reast Cancer.


Lung Cancer/

*TE in MedicalCancer+ AdancedPancreatic Cancer

0

Catheter-&elated

Thrombosis+ Earlreast Cancer Patient4

Catheter-&elatedThrombosis+ "arian

Cancer Patient2

*TE in Pregnanc+

Throid CancerPatient3

*TE in Pregnanc+Melanoma Cancer

Patient1

"eriew

The international *TE and cancer guidelines mobile

app ma be used as a decision tool when reiewingthe case studies 5%ree %or download6 T", venous thromboembolism6



International S!eaer 0isclosres< #r #abinger

• 9onoraria for lectures and advisory board meetings from Pfi:er,

8ayer and 8oehringer +ngelheim6



Overvie%



:earning Objectives

• (t the end of the program, participants will be able to@o )escribe the ris3s and conse*uences of T", including )T, P", and CRT

in women with cancer

o

(pply international clinical practice guidelines and appropriate treatmentrecommendations for established and recurrent T" in women with cancer

o "stablish personali:ed T" prophylaxis in women with cancer, in both

surgical and medical settings

o "valuate challenging clinical scenarios specific to women with cancer and

thrombosis, including hormonal therapies and pregnancy

CRT, catheter-related thrombosisG )T, deep vein thrombosisG P", pulmonary embolismG T", venous thromboembolism6



&genda

• 8urden and incidence of womenEs cancer

• +mpact of'relationship between thrombosis and cancer

• Ris3 factors for T" in cancer

• Treatment options for T"• +nternational clinical practice guidelines for T" in cancer patients

• Ta3e-home messages and HI(

• Case studies

T", venous thromboembolism6



Wh1 shold %e care abot %omen %ith cancer9



6rden of Women3s Cancers

• The burden of cancer is increasing as a result of an aging

populationo This is concerning for women, as they tend to live longer

• !J6. million women worldwide were living with cancer

in ./!.o 26J million new cancer cases in women

o 462 million cancer deaths in women

World 9ealth Organi:ation6 WomenEs 9ealth 7act &heet, ./!46

+nternational (gency for Research on Cancer, ./!.6

T C &ff ti W



To! Cancers &ffecting Women

World%ide


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)ncidence 5>6 Breast

Colorectum

(ung

Cer"i)

Endometrium

*tomach

+"ary

Thyroid

(i"er

,on-odg.in/slymphoma

(eu.emia0ancreas

Esophagus

1idney

Brain ner"oussystem

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To! Cancers &ffecting Women

World%ide


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Mortalit 5>6 Breast

(ung

Colorectum

Cer"i)

*tomach

(i"er

0ancreas

+"ary

Esophagus

(eu.emia

,on-odg.in/s

lymphomaBrain ner"oussystem

Endometrium

1idney

Thyroid



What is the im!act of4relationshi! bet%een

thrombosis and cancer9



Thrombosis and Cancer Incidence

• T" is a fre*uent and serious complication in cancer patientso Second most common case of death after metastasis#!

Copyright K !/14J1/ OP+C .L'/.'./!.#6

CRT, catheter-related thrombosisG )T, deep vein thrombosisG P", pulmonary embolismG T", venous thromboembolism6!6 ?horana ((, et al6 # $hromb %aemost .//[email protected] .6 7arge ), et al6 $hromb es ./!/G!.5&uppl .#@&!/L-!26

46 7alanga (, Machars3i 6 &nn 'ncol .//5G!2@212-J/!6 B6 %onreal %, et al6 # $hromb %aemost .//2GB@!15/-26

Cancer• *TE 5?*T@ PE@ or C&T6

in 4> to ,> o%cancer patients,

• *TE at autops in

2> o% cancer

patients#

*TE• ,> o% *TE patients

hae actie cancer4

• 4> to 1,> o%patients with

idiopathic *TE haean underling cancer#



Effect of 2TE on Srvival in Cancer #atients


evitan D, et al6 Medicine (Baltimore) !111GJL5#@.L5-1!6

Likelihood o% ?eath A%ter ospitaliBation

2TE $ d M j 6l di M



2TE $ecrrence and Major 6leeding MoreFre?ent in Cancer #atients

9R, ha:ard ratioG %W9, low molecular weight heparinG T", venous thromboembolism6

Prandoni P, et al6 Blood .//.G!//!/#@4BLB-L6

:04,D treatment with LM7 9 war%arin %or # months

&ecurrent *TE Ma;or leeding

Cancer

o Cancer

Cancer

o Cancer

• Cancer patients with T" are more li3ely to develop recurrent

T" and ma<or bleeding during anticoagulant treatment than

patients without cancer

#2-month cumulati"e incidence2!$' "s$ $&

56 7$2

#2-month cumulati"e incidence#2$4 "s$ 4$%

56 2$2



2ircho%3s Triad in Cancer #atients

+n !L52 irchow described three categories of factors

thought to contribute to thrombosis

• Endothelial damage 8

&hift to procoagulant endothelium 8 +nvasion of cancer cells into vessel wall

• Stasis of blood 8 7re*uent immobili:ation, surgery

8 Compression of blood vessels by tumor

• Changes in blood constitents 8 (ctivation and'or release of clotting proteins and blood cells

;reen ?8, &ilverstein R6 %ematol 'ncol *lin +orth &m !112G!/.#@B11-54/6

Prandoni P, et al6 %aematologica !111GLB5#@B4J-B56

Ric3les 7R, 7alanga (6 $hromb es .//!G!/.2#@.!5-.B6



Mechanisms of Thrombosis in Cancer



Mechanisms of Thrombosis in Cancer

)cont3d+

+, interleu3inG TD7, tumor necrosis factorG ";7, vascular endothelial growth factor6

&hel3e (R, ?horana ((6 Drug Disco $oda" Dis Mech ./!!GL!-.#e41-B56



What are the ris factors for 2TE in cancer9




$is Factors for 2TE in Cancer

• Treatment-related factors

8 Recent ma<or surgery

8 Current hospitali:ation

8 Central venous catheter

8 (ctive chemotherapy

8 &ctive hormonal thera!1 8 Current or recent antiangiogenic

therapy thalidomide, lenalidomide,

bevaci:umab#

8 Current "&(

• #atient-related factors 8 Older age especially N25 years#

8 Race 8lac3 N (sian#

8 Obesity

8 Comorbidities

8 Prior history of T" 8 9eritable prothrombotic mutations

8 #regnanc1

• Cancer-related factors

8 Primary site of cancer especially

pancreatic, ;+, brain, lung,

g1necological, renal, hematological#

8 +nitial 4 to 2 months after diagnosis

8 Current metastatic disease

"&(, erythropoiesis-stimulating agentG ;+, gastrointestinalG T", venous thromboembolism6

(y C, et al6 Blood ./!/G !!2.B#@54!J-L.6

7arge-8ancel ), et al6 ambam Maimonides Med # ./!BG5B#@e//B!6?horana ((, et al6 Blood .//LG!!!!/#@B1/.-J6

yman ;9, et al6 # *lin 'ncol .//JG.54B#@5B1/-5/56



$ate of 2TE b1 Cancer Site

#ooled incidence rates )!er (;;; !erson-1ears+ of 2TE !er t1!e of cancer


Timp =7, et al6 Blood ./!4G!..!/#@!J!.-.46



$ate of 2TE b1 Cancer Stage

• 9igher rates of T" in metastatic disease


Chew 9?, et al6 &rch Intern Med .//2G!22B#@B5L-2B6

Timp =7, et al6 Blood ./!4G!..!/#@!J!.-.46



#redictive Model for 2TE in Cancer

An aggregate score o% # indicates high risk5/> risk o% *TE6 in outpatients with cancer

Patient Characteristics &isk$core

$ite o% cancer

*er high-risk 5stomach@ pancreas6 ,

igh-risk 5lung@ lmphoma@ gnecologic@ bladder@testicular6

1

Pre-chemotherap platelet count#2@!mm#

1

emoglobin leel H1 g!dL or use o% E$A 1

Pre-chemotherap leukocte count11@!mm#

1

M) #2 kg!m, 1

8%+, body mass indexG "&(, erythropoiesis-stimulating agentG T", venous thromboembolism6

?horana (( , et al6 Blood .//LG!!!!/#@B1/.-J6

,ote6 low ris. 9score !: intermediate ris. 9score #-2: and high ris. 9score 7:




Rao, et al6 +n@ ?horana ((, eds6 *ancer-&ssociated $hrombosis6 Dew or3G .//L@!21-1.6

&

'

34

7

2

#

!

Chemotherapy Ris3 in cancer population

Remission

Ris3 in general population

Time

)iagnosis

%etastasis

"nd of life9ospitali:ation

R i s 3 o d d s r a

t i o #

$is of 2TE 2aries Over Cancer Evoltion

Patients reIuire %reIuent monitoring and indiidualiBed

treatment



What are the treatment o!tions for 2TE9

What do international gidelines recommend for 2TE

treatment and !ro!h1laxis in cancer !atients9




2TE Treatment O!tions

Pharmacologic 5prophla(is and treatment6

Low-molecular-weightheparins 5LM7s6 ;alteparin Eno)aparin

,adroparin Tin<aparin

)ndirect %actor Jainhibitor =ondaparinu)

Thromboltics oel oralanticoagulants 5"ACs6 Direct factor Xa

inhibitors

>pi)a?an Edo)a?an 5i"aro)a?an Direct factor IIa inhibitor

;a?igatran

Kn%ractionated heparin 5K6

*itamin antagonists 5*As6 Warfarin

>cenocoumarol 0henprocoumon

onpharmacologic 5prophla(is6

Graduated compression stockings)ntermittent pneumatic compression

7eed for 6est Treatment and Effective



7eed for 6est Treatment and Effective

#revention of 2TE in Cancer #atients

• &everal scientific societies have issued guidelines@ 8 (merican College of Chest Physicians (CCP#

8 (merican &ociety of Clinical Oncology (&CO#

8Dational Comprehensive Cancer Detwor3 DCCD#

8 "uropean &ociety of %edical Oncology "&%O#

8 +nstitut Dational du Cancer &OR-+DCa#

8 +nternational %yeloma Wor3ing ;roup +%W;#

8 +talian (ssociation of %edical Oncology (+O%#

8 +nternational +nitiative on Thrombosis and Cancer +T(C-C%"#


!6 7arge et al6 # $hromb %aemost ./!4G!!!#@52-J/6

.6 )ebourdeau et al6 # $hromb %aemost ./!4G!!!#@J!-L/6

46 7arge et al6 $hromb es ./!/G!.5&uppl .#@&!/L-!26

*arious methodologies@ diOerent Iuestions

Low leel o% implementation1-#

Clinical Isses and =alit142alidation



Clinical Isses and =alit142alidation

of 2arios 2TE 5idelines

$pdated in ./!B6

(CCP, (merican College of Chest PhysiciansG (+O%, +talian (ssociation of %edical OncologyG (&CO, (merican &ociety of Clinical OncologyG

CRT, catheter-related thrombosisG CC, central venous catheterG )T, deep vein thrombosisG DCCD, Dational Comprehensive Cancer Detwor3G

P", pulmonary embolismG &OR, &tandards, Options I Recommendations 7rench national guidelines#G T", venous thromboembolism6

7arge-8ancel ), et al6 ambam Maimonides Med # ./!BG5B#@e//B!6

@ @

International 5idelines<



International 5idelines<

Clinical Isses

!6 +nitial treatment first 5 to !/ days# of established T"

.6 "arly maintenance N!/ days to 4 months# and long-term treatment

N4 months# of established T"

46 Treatment of T" recurrence with ?(, %W9, and vena cava filter

B6 Prophylaxis of T" in surgical cancer patients56 Prophylaxis of T" in medical cancer patients special focus on lung,

pancreatic, and myeloma patients#

26 Treatment of established CRT

J6 Prophylaxis of CRT

L6 &pecific cases@ brain tumors, neurosurgery, renal failure, thrombocytopenia,and pregnant women with cancer

CRT, catheter-related thrombosisG %W9, low molecular weight heparinG T", venous thromboembolism6

7arge et al6 # $hromb %aemost ./!4G!!!#@52-J/6

)ebourdeau et al6 # $hromb %aemost ./!4G!!!#@J!-L/6

International %oring gro!< .B multidisciplinary experts, . methodologists, ! nurse, 4 patients,

B. independent reviewers

International 2TE and Cancer 5idelines




Mobile &!!

• +T(C-C%" developed a clinical tool in the form of a

mobile application, based on the international guidelineso &imple decision-tree algorithm to assist with treatment strategies

o "ncourages the <udicious and appropriate use of anticoagulantsas T" prophylaxis and treatment in patients with cancer

o (vailable to download for free in the (pp &tore and on ;oogle

play

+T(C-C%", +nternational +nitiative on Thrombosis and CancerG T", venous thromboembolism6



Treatment of established 2TE




Wh1 Treat9

• To prevent fatal T"

• To prevent recurrenceo Rates of T" recurrence and ma<or bleeding are particularly

high in cancer patients compared with noncancer patients .- to 5-fold increase in the rate of T" recurrence

.- to 2-fold increase in the rate of ma<or bleeding






=(< Initial Treatment of Established 2TE in #atients

%ith Cancer

• Corres!onds to the first * to (; da1s of anticoaglation

• $79 Q ?( vs6 %W9 Q ?(

o 8oth are associated with high rates of relapse and ma<or bleeding

Relapses@ 8F@ A :MW@

%ortality@ 8F@ B :MW@

• 7ondaparinux vs6 W%9 vs6 $79

%W9, low molecular weight heparinG $79, unfractionated heparinG ?(, vitamin ? antagonistG T", venous thromboembolism6


vs' 8F@ 2D& vs' :MW@ 2D&

Relapses 7ondaparinux 8F@ 7ondaparinux N :MW@

8leeding 7ondaparinux A 8F@ 7ondaparinux A :MW@

%ortality 7ondaparinux A 8F@ 7ondaparinux A :MW@


= f



• Recommendations@o %W9 is recommended, although fondaparinux and $79 can

also be used

%W9s and fondaparinux are easier to use than $79

o ena cava filters may be considered in the case ofcontraindication for anticoagulation or recurrence under optimalanticoagulation

o Thrombolysis may be considered only on a case-by-case basis,with specific attention to contraindication, especially bleeding ris3

=(< Initial Treatment of Established 2TE in #atients

%ith Cancer )cont3d+

%W9, low molecular weight heparinG $79, unfractionated heparinG T", venous thromboembolism6





=.< Earl1 Maintenance and :ong-Term Treatment

• "arly maintenance treatment corresponds to the time beyond

days 5 to !/, up to the third month of anticoagulation

• ong-term treatment corresponds to treatment indicated

beyond the third month of anticoagulation

• +n noncancer patients, a ?( or DO(C is standard therapy

• +n cancer patients, ?( increases ris3 of relapse and bleeding

o %eta-analyses have shown that %W9 alone vs6 heparin followed

by ?( significantly reduces the ris3 of T" recurrence by 5/S

with no increased ris3 of bleeding and no effect on mortality

%W9, low molecular weight heparinG DO(C, novel oral anticoagulantG ?(, vitamin ? antagonistG T", venous thromboembolism6





• %W9s used in studies comparing early maintenance

and long-term treatment by %W9 vs6 ?(

,ote6 Idraparinu) 9not registered: was found to ?e as eAecti"e as V1> with the samerate of ?leeding e"ents$

=.< Earl1 Maintenance and :ong-Term Treatment )cont3d+

%W9, low molecular weight heparinG ?(, vitamin ? antagonistG T", venous thromboembolism6





• %eta-analysis of studies comparing early maintenance


$ecrrence


C+, confidence intervalG %W9, low molecular weight heparinG ?(, vitamin ? antagonistG T", venous thromboembolism6





• %eta-analysis of studies comparing early maintenance


6leeding


C+, confidence intervalG %W9, low molecular weight heparinG ?(, vitamin ? antagonistG T", venous thromboembolism67arge et al6 # $hromb %aemost ./!4G!!!#@52-J/6




• )uration of anticoagulationo One study evaluated patients with active cancer and a first episode

of )T who received %W9 for 2 months and were then divided

into 4 groups@

o +n patients with )T, after 2 months of anticoagulation@ $se of $& )oppler was not reliable and remains debated at this stage

$se of )-)imer was not well documented enough to determine the need

for further anticoagulation

o Do study compared 4 vs6 2 months of %W9

$eslts of 0!lex 8ltrasond Examination $ela!se Major 6leeding

Residual T" continuation of anticoagulation !B6.S B6.S

Residual T" discontinuation of anticoagulation .!61S !62S

Do residual T" discontinuation of anticoagulation .6LS !61S


)T, deep vein thrombosisG %W9, low molecular weight heparinG T", venous thromboembolism67arge et al6 # $hromb %aemost ./!4G!!!#@52-J/6




• Recommendations@o %W9s are preferred over ?(s

o %W9s should be used for a minimum of 4 months

)aily subcutaneous in<ection may represent a burden for patients

o (fter 4 to 2 months, termination or continuation of %W9 or ?(

should be based on individual evaluation of the benefit'ris3 ratio,

tolerability, patient preference, and cancer activity


%W9, low molecular weight heparinG ?(, vitamin ? antagonistG T", venous thromboembolism67arge et al6 # $hromb %aemost ./!4G!!!#@52-J/6




=/< Treatment of 2TE $ecrrence 8nder &nticoaglation

• Recommendations@ 8 Three options can be considered@

( switch from a ?( to a %W9 when treated with ?(

(n increase in the %W9 dose when treated with a %W9

+n some patients, vena cava filter insertion

%W9, low molecular weight heparinG ?(, vitamin ? antagonistG T", venous thromboembolism67arge et al6 # $hromb %aemost ./!4G!!!#@52-J/6

$ l f 7 O l & ti l t & t 9



$ole of 7e% Oral &nticoaglant &gents9

• DO(C trials have demonstrated noninferior efficacy compared

to ?( in cancer patientsG available data are scarce

• Do comparison against %W9, which is the standard for

cancer patients a current study is underway#

• )rug interactions may be clinically important in cancer patients

• Do recommendations at this time in the absence of data

• Deed for prospective studies

%W9, low molecular weight heparinG DO(C, novel oral anticoagulantG ?(, vitamin ? antagonist6

&horta D, Connors =%6 'ncologist ./!BG!1!#@L.-1467arge et al6 # $hromb %aemost ./!4G!!!#@52-J/6



#revention of 2TE in srgical cancer !atients


2TE in Cancer #atients 8ndergoing



2TE in Cancer #atients 8ndergoing

Srger1

• Cancer patients undergoing surgery have twice the ris3

of postoperative T" compared to noncancer patients

undergoing the same surgery!

• The following were found to be independent ris3 factorsfor T" in female mastectomy patients.@o Obesity

o enous catheteri:ation

o Prolonged operative time N4 hours#

o +mmediate reconstruction


!6 Ric3les 7R, evine %D6 &cta %aematol .//!G!/2!-.#@2-!.6

.6 Tran 89, et al6 Breast ./!4G..B#@BBB-L6

&t1!ical :ocali"ation of 2TE in Cancer Com!ared



• Retrospective, single-institution cohort study• DA!1.! medical records of cancer patients

solid T Q chemotherapy#

.4/

(4/

(4/

)T, deep vein thrombosisG &T, superficial vein thrombosisG P", pulmonary embolism6

!6 ?a33ar , et al6 ancet !121G.J2!B#@.4/-.6.6 )i Disio %, et al6 $hromb %aemost ./!/G!/B5#@!/B1-5B6

7atral histor1 follo%ing

major srger1(

Incidental 2TE in cancer

%ith chemothera!1.

to Major Srger1 Setting

#1>

,.>1#>

1>

0>

.>4 2 Lower

limbs?*T alone

PE alone

PE withlower limbs

?*T

Portal orsplanchniceins

Lowerlimbs ?*T

9 $*T

)liac-caaein &enal

eins

Kpperlimbs ?*T

2TE and Mortalit1 in Cancer #atients



1

8ndergoing Srger1

$ates of 2TE and Mortalit1 %ith 2TE in #atients 8ndergoing

Major Cancer Srger1 in the 8nited States )(-.;;+

C+, confidence intervalG "(PC, estimated annual percentage changeG %C&, ma<or cancer surgeryG T", venous thromboembolism6Trinh H, et al6 #&M& urg ./!BG!B1!#@B4-16

• .,5/L,1!2 patients

• Overall T" rate was !64S

• T" incidence B6/S per year

• )ecreased mortality from T"


= S C



=< Srgical Cancer #atients

• )rug regimens evaluated in clinical trials of

thromboprophylaxis in surgical cancer patients

%W9, low molecular weight heparinG T", venous thromboembolism67arge et al6 # $hromb %aemost ./!4G!!!#@52-J/6


= S i l C # ti t ) t3d+



• %W9 or $79 vs6 placebo or no treatmento %W9 or $79 N placebo or no prophylaxis

o Rate of any bleeding with %W9 N placebo or no treatment

• %W9 vs6 $79o &ame efficacy for %W9 vs6 $79

%W9 once daily A $79 three times daily

%W9 once daily N $79 twice daily

o Trend toward less bleeding with %W9

%W9, low molecular weight heparinG $79, unfractionated heparinG T", venous thromboembolism67arge et al6 # $hromb %aemost ./!4G!!!#@52-J/6

=< Srgical Cancer #atients )cont3d+


= S i l C # ti t ) t3d+



• %W9 doseso 9igh-dose dalteparin 5/// +$# superior to low-dose .5// +$#

o Do significant difference for bleeding ris3 B62S vs6 462S#

• "xtended-duration prophylaxiso %eta-analysis@ B wee3s of %W9 decreased postoperative ris3 of T"

o Trend toward increased bleeding ris3 in extended prophylaxis group




= S i l C # ti t ) t3d+



• Recommendationso $se of %W9 once daily or low-dose $79 three times daily is

recommended

&hould be started !. to . hours preoperatively and continued for at

least J to !/ days %W9 once daily is more convenient

Do data allowing conclusions regarding superiority of one type of

%W9 over another

o $se of the highest prophylactic dose of %W9




= S i l C # ti t ) t3d+



• Recommendations contEd#o "xtended prophylaxis B wee3s# after ma<or laparotomy may be

indicated in patients with cancer who have a high ris3 of T" and

low ris3 of bleeding, as ris3 of T" extends beyond hospital

dischargeo %echanical methods are not recommended as monotherapy,

except when pharmacological methods are contraindicated


T", venous thromboembolism67arge et al6 # $hromb %aemost ./!4G!!!#@52-J/6



#revention of 2TE in medical cancer !atients


Chemothera!1 in Cancer and



!1

Thrombosis

• Chemotherapy is strongly associated with T"!

o Cancer alone is associated with a B6!-fold ris3

o Chemotherapy increases the ris3 265-fold

• (ntiangiogenic agents such as bevaci:umab, which are

being used or investigated to treat breast and ovarian

cancers, are associated with very high rates of T".

•+%i)s thalidomide in particular# used to treat myelomaare also associated with very high rates of T".,4

+%i)s, immunomodulatory drugsG T", venous thromboembolism6

!6 9eit =(, et al6 &rch Intern Med .///G!2/2#@L/1-!56

.6 Cohen (T, et al6 $hromb es ./!!G!.J&uppl 4#@&5-L6

46 Palumbo (, Palladino C6 $her &d Drug a/ ./!.G45#@.55-226

#rothrombotic Effects of Chemothera!1



#rothrombotic Effects of Chemothera!1

(T, antithrombinG +, interleu3inG P(+, plasminogen activator inhibitorG T7, tissue factorG TD7, tumor necrosis factorG ";7, vascular endothelial growth factor69addad TC, ;reeno "W6 $hromb es .//2G!!L5#@555-2L6


=* Medical Cancer #atients



=*< Medical Cancer #atients

• Do study evaluated thromboprophylaxis specifically in

hospitali:ed medical cancer patients

• Patients hospitali:ed for acute medical disease with reduced

mobility 5S to !5S were cancer patients#o %W9 and $79 had similar efficacy and safety

o %W9 and fondaparinux N placebo with a nonsignificant trend toward

increased bleeding ris3



=*< Medical Cancer #atients )cont3d+




• (mbulatory patients treated with chemotherapyo 5 randomi:ed studies compared %W9 vs6 placebo or no treatment@

)ecreased rate T" without an excess of bleeding in patients with locally

advanced or metastatic pancreatic cancer at subtherapeutic dosages# or

locally advanced or metastatic lung cancer

Do effect on T" in patients with metastatic breast cancer

%W9 may increase bleeding ris3, particularly in thrombocytopenia






• Recommendationso Prophylaxis with %W9, $79, or fondaparinux is recommended

in hospitali:ed medical cancer patients with reduced mobility

o +n patients receiving chemotherapy, prophylaxis is not

recommended routinelyo T" primary pharmacological prophylaxis may be indicated in

patients with locally advanced or metastatic pancreatic or lung

cancers who are treated with chemotherapy and have low

bleeding ris3







• Recommendations contEd#o T" prophylaxis is recommended for myeloma patients treated

with +%i)s thalidomide or lenalidomide# combined with steroids

and'or chemotherapy

?( at low or therapeutic doses, %W9 at prophylactic dose, andlow-dose (spirin have shown similar effects in preventing T"

+%i)s, immunomodulatory drugsG %W9, low molecular weight heparinG ?(, vitamin ? antagonistG T", venous thromboembolism67arge et al6 # $hromb %aemost ./!4G!!!#@52-J/6




Treatment and !revention of C$T

CRT, catheter-related thrombosis6

C$T Is Common



C$T Is Common

• +ncidence of symptomatic CRT is /S to .LS in cancer

patients

• %ay lead to P" in !/S to !5S of patients and loss of

central venous access in !/S of patients

CRT, catheter-related thrombosisG P", pulmonary embolism6

erso %, (gnelli ;6 # *lin 'ncol .//4G.!!1#@4225-J56)ebourdeau P, et al6 # $hromb %aemost ./!4G!!!#@J!-L/6

0efinition of C$T



0efinition of C$T

• %ural thrombus extending from catheter into the lumen

• Catheter dysfunction without mural thrombus

o Pinch off o 7ibrin sheath

o )istal tip thrombus


Sleeve thrombus Mural thrombus

Distal tip thrombusFibrin sheath

True catheter-related thrombosis

False catheter-related thrombosis

False C$T



False C$T

Pinch-off syndrome occurs when

the catheter is compressed between

the first rib and the clavicle, causing

an intermittent mechanical occlusion

for both infusion and withdrawal

The evolving ris3 is a brea3ing of

the catheter, leading to its

migration to the pulmonary arteries


False C$T )cont3d+



False C$T )cont d+

7ibrin sheath occurs in about

J/S of cases within the firstmonth after catheter insertion

)istal tip thrombus withoutany mural component

Treatment U anticoagulant

Treatment A fibrinolytics CRT, catheter-related thrombosis6

#h1sio!atholog1 of C$T



#h1sio!atholog1 of C$T

Thrombs l1sis

in / ot of

cases

Thrombsgro%th

Thrombogenic factor

local or s1stemic

Catheter insertion 2asclar %all

injr1

Thrombs formation

In some cases, thrombs occrs in a dela1ed

manner a%a1 from the catheter insertion !oint


Catheters 8sed in Oncolog1



Catheters 8sed in Oncolog1

ong-term CC

Without

implanted port

With

implanted port

Open-ended

With ;roshong

system

TunneledDon-tunneled

P+CC lines With a sleeve Without a sleeve

8roviac catheter 9ic3man catheter

CC, central venous catheterG P+CC, peripherally inserted central catheter6

C$T $is Factors



C$T $is Factors

• +nsertion-relatedo P+CC lines N CC with implanted port

o &ubclavian CC N <ugular CC

o )-)imer levels after insertion fibrin lysis#

• Patient-relatedo 7actor and prothrombin mutation

• Cancer-relatedo Dot well-documented

CRT, catheter-related thrombosisG CC, central venous catheterG P+CC, peripherally inserted central catheter6)ebourdeau et al6 # $hromb %aemost ./!4G!!!#@J!-L/6


=>< Treatment of Established C$T



=>< Treatment of Established C$T

Do prospective randomi:ed studies

• Recommendationso (nticoagulant treatment is recommended for a minimum of

4 months %W9s are suggested

?(s can also be used in the absence of direct comparisons of these

two types of anticoagulants

CRT, catheter-related thrombosisG %W9, low molecular weight heparinG ?(, vitamin ? antagonistG T", venous thromboembolism6)ebourdeau et al6 # $hromb %aemost ./!4G!!!#@J!-L/6




=< #revention of C$T



=< #revention of C$T

+n randomi:ed trials, %W9 did not show any benefitG in meta-

analyses, ?( was not found to be beneficial vs6 placebo or no

treatment'prophylaxis

o ?( may be used in certain circumstances when the ris3 of

symptomatic CRT is very high according to the physicianEs <udgment

CRT, catheter-related thrombosisG %W9, low molecular weight heparinG ?(, vitamin ? antagonistG T", venous thromboembolism6)ebourdeau et al6 # $hromb %aemost ./!4G!!!#@J!-L/6


=< #revention of C$T )cont3d+



=< #revention of C$T )cont d+

• Recommendationso $se of anticoagulant treatment for routine prophylaxis of CRT is

not recommended

8leeding ris3 with anticoagulants

o CCs should be inserted on the right side, in the <ugular vein,

and the distal extremity of the CC should be located at the

<unction of the superior vena cava and the right atrium

CRT, catheter-related thrombosisG CC, central venous catheterG T", venous thromboembolism6)ebourdeau et al6 # $hromb %aemost ./!4G!!!#@J!-L/6



2TE in cancer and !regnanc1


Cancer and #regnanc1



Ca ce a d eg a c1

• Cancer in pregnancy presents ma<or diagnostic and

therapeutic challengeso &olid tumors constitute the ma<ority of cancers diagnosed at gestation,

while hematological malignancies are less commonly reported

• %aternal survival is considered the main concern, while

reduction in treatment-related fetal toxicity should be

attempted

• Prevention and management of thrombotic and

hemorrhagic complications may affect outcomes

%orice P, et al6 ancet ./!.G4J11L!5#@B15-26

Thrombotic Manifestations



• T" occurs in about ! in !/// pregnancies

• The hypercoagulability state in pregnant women with

cancer may lead to@

o Placental thrombosis and fetal growth restriction or losso %aternal and fetal'neonatal morbidity and death

T", venous thromboembolism6=acobsen (7, et al6 &m # 'bstet !"necol .//LG!1L.#@.446e!-J6

2TE #resentation in #regnanc1



g 1

Most 2TEs occr dring the first > %ees !ost!artm

T", venous thromboembolism6=acobsen (7, et al6 &m # 'bstet !"necol .//LG!1L.#@.446e!-J6

DA2!5

(. ., /> ( > (.;

(;

.;

/;

,;

*;

>;

F;

G;

E;

0eliver1

#ost-!artm&nte-!artm

Wees

2 T E )

n +


=G< S!ecial #o!lations< #regnant Women %ith Cancer



= ! ! g

• Do study evaluated the treatment or prophylaxis of T"

in pregnant women with cancer

• Recommendation@o

&tandard treatment for established T" and prophylaxis shouldbe implemented

Contraindication of ?( during pregnancy

?(, vitamin ? antagonistG T", venous thromboembolism67arge et al6 # $hromb %aemost ./!4G!!!#@52-J/6

Tae-@ome Messages



Tae @ome Messages

• 7ew clinicians appear to be aware of the higher ris3 of T" in cancer

patients, and this contributes to high morbidity and mortality

• 8reast, lung, and gynecological cancers are the most common cancers

associated with T" in women

• %any other factors can increase the ris3 of T" among cancer patients,

including obesity, advanced disease, surgery, chemotherapy, and CCs

• Pregnancy and use of hormone therapies can also increase the ris3 of T",

which is particularly concerning for women

• (ppropriate prophylaxis and treatment of T" in women with cancer can be

accomplished by using %W9s, $79, ?(s, or fondaparinux, as

recommended by the ./!4 international clinical practice guidelines

CC, central venous catheterG %W9, low molecular weight heparinG $79, unfractionated heparinG?(, vitamin ? antagonistG T", venous thromboembolism6



=H&



Case /

T" in &urgical Cancer@

Colorectal Cancer Patient


:earning Objectives



g j

• (fter completing this case, participants will be able to@o (pply appropriate thromboprophylaxis for a woman undergoing

colorectal surgery for cancer

o "valuate strategies for appropriate treatment of established T"


#atient #rofile



• J.-year-old woman

• 8%+@ .5 3g'm.

• 9istory of thrombosed hemorrhoids and intermittent rectal bleeding

• &he previously had a lower-extremity )T after a long-haul flight

!/ years earlier#, treated with anticoagulation• ( colonoscopy revealed a mass in her ascending colon with severe

lymph node involvement

• "levated C"( levels

• 8iopsy confirmed adenocarcinoma

• &he was given preoperative neoad<uvant chemotherapy

• Colorectal surgery planned

8%+, body mass indexG C"(, carcinoembryonic antigenG )T, deep vein thrombosis6



0a1 of Srger1



1 g 1

• What strategy would you recommend as perioperative T"

prophylaxis in this patient for colorectal surgery#F Do thromboprophylaxis needed immediately before surgery

%echanical prophylaxis only, no pharmacotherapy needed immediately

before surgery

Pharmacotherapy started preoperatively

8oth mechanical and pharmaceutical prophylaxis immediately before

surgery

Other


5ro! 0iscssion



• Which anticoagulant agent would you chooseFo Which doseF

o When would you startF

o

7or how longF



5ro! 0iscssion



• 9ow would you manage this patientF

Smmar1



• )T is reported to be common among women undergoing surgery for

gastrointestinal cancer

• +f the colorectal cancer is growing into nearby organs, the ovaries, uterus,

and cervix are also removed during surgery

• The incidence of T" is highest in the first few months after cancer

diagnosis, with increased ris3 of chemotherapy and ma<or surgery

• T" prophylaxis with %W9 or $79 should be started !. to 4 hours

preoperatively and continued for at least J to !/ days 0 extended duration B

wee3s# after ma<or laparotomy may be indicated in patients with cancer who

have a high ris3 of T" and low ris3 of bleeding

• %echanical methods are not recommended as monotherapy, except whenpharmacological methods are contraindicated

• +n the case of established T", %W9s are preferred over ?(s for early

maintenance and long-term treatment, and should be used for a minimum of

4 months

)T, deep vein thrombosisG %W9, low molecular weight heparinG $79, unfractionated heparinG ?(, vitamin ? agonistG T", venous thromboembolism6

=estions and Conclsion

Women trombosis and Cancer

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