Congres BVPV 2019 RESPIRATOIRE ONCOLOGIE LONGKANKER … · Rookstop plannen Van der Aalst CM, van...
Transcript of Congres BVPV 2019 RESPIRATOIRE ONCOLOGIE LONGKANKER … · Rookstop plannen Van der Aalst CM, van...
Preventie en Screening
Congres BVPV 2019RESPIRATOIRE ONCOLOGIE
LONGKANKER WAAR STAAN WE?
22-05-2019
PREVENTIE EN SCREENING
1. Achtergrond Preventie
2. Longkankerscreening
3. NLST
4. NELSON
5. Hoe nu verder in de praktijk?
22-05-2019
PREVENTIE
Pneumologie voor Verpleegkundigen 2011 4
LONGKANKER
Jaar: 2012
1.824.701 nieuwe gevallen wereldwijd
Longkanker in België
www.kankerregister.org 2019
Data source: http://www.kankerregister.org
(LUNG) Cancer screening-Belgium
Smoking facts in Belgium
http://blogs.nature.com/ofschemesandmemes/2014/09/11/the-big-issues-affecting-lung-cancer-worldwide
Sterfte per 100,000 personen
Stagnerend rookgedrag
in
Vlaanderen/België
Roken en rookstop
• Cijfers
• Opleiding
• Rookstop en CT screening
https://rookstop.vrgt.be/
Rookstop plannen
Van der Aalst CM, van den Berg KAM, Willemsen MC et al Thorax 2010;65:600-605
Van der Aalst CM, van den Berg KAM, Willemsen MC et al Thorax 2010;65:600-605
Baird AM for LUCE, Lung Cancer Screening: a patient’s perspective, ERS/EAPM Meeting Brussels 2019
Preventie
• Secundaire preventie
– Bij detectie van premaligne letsels
• Teriaire preventie
– Na behandeling van primaire longkanker
De Flora S et al Trends Pharmcol Sci 2016;37:120-142; Dresler C et al J Thorac Oncol 2018;13:603-605
31 MEI
WNTD
SCREENING
24
“Lung cancer screening aims to reduce lung
cancer related mortality with relatively limited
harm through early detection and treatment”
Van der Aalst CM, ten Haaf K, de Koning H. Lancet Respir Med 2016;4:749-61
LDCT lung cancer screening RCTs
Van der Aalst CM, ten Haaf K, de Koning H. Lancet Respir Med 2016;4:749-61
X
X
X
X
V
V
?
?
Total number of deaths due to lung cancer :
247 vs 309 deaths/100.000 pers.yrs (CT vs RX group)
Relative reduction in LC mortality of 20.0% or HR=0,80 ( 95%CI 0,73-0,93)
Reduction in all cause mortality of 6,7% or HR=0,93 (95% CI 0,86-0,99)
Number Needed to Screen with LDCT to prevent 1 death : 320
LDCT RCT NLST 2011
Aberle DR et al New Engl J Med 2011
LDCT LUNG CANCER SCREENING
• Benefits
• LC mortality reduction
• Reduction stages III-IV
• Harms
• False positives
• Overdiagnosis
• Overtreatment
• Radiation exposure
• Costs
• QOL
• Smoking behaviour
Janes S, De Koning H, IASLC WCLC 2016 MTE: How to implement screening?
Baldwin R, Callister MEJ. Clin Oncol 2016;28:672-681
Field J, Duffy SW, Devaraj A, Baldwin DR. Lancet Respiratory 2016;4:685-7
Yousaf-Khan U et al Thorax 2017;160:311-320
Nodule management
• NELSON nodule management plan
Heuvelmans M.A. et al, J Thorac Imaging 30, 101-107, 2015
NODULE CATEGORIZATION BASED ON SIZE AND DENSITY (NEW NODULES)
AND GROWTH RATE (EXISTING NODULES) IN THE NELSON TRIAL
OVERVIEW OF THE NELSON SCREENING PROTOCOL
NELSON : 5,5 YEARS CALCULATIONS
1st screening result
Negative
Indeterminate
Positive
Risk screen-detected lung cancer
1,0%
5,7%
48,3%
Horeweg N et al Eur Respir J 2013;42:1659-67
ERS/ESR White Paper LC Screening 2015
• Further refinements to increase quality, outcome and cost-effectiveness:
• Inclusion of risk models
• Reduction of effective radiation dose
• Computer-assisted volumetric measurements
• Assessment of comorbidities (COPD/Vascular calcifications)
• Central registry, including biobank, preferably on a European level
Kauczor H et al Eur Respir J 2015;46:28-39
34
Field JK et al Thorax 2016;71:161-70
High Risk
In
11,5% of positive responders
35
36
Humphrey LL et al Ann Intern Med 2013;159:411-420De Koning HJ et al Ann Intern Med 2014;160:311-320
• Lung Cancer Low-Dose CT Screening in the USA
• Percentage of eligible smokers who had low-dose CT in the past 12 months remained low and constant:
• 2010: 3,3%
• 2015: 3,9%
• Of the 6.8 million U.S. smokers eligible for low-dose CT screening, only 262,700 received it.
37
Data from the Surveillance & Health Services Research, American Cancer Society (ACS).Jemal A, Fedewa SA. Lung cancer screening with LDCT in the United States – 2010-2015. JAMA Oncol 2017early release online 2 Feb 2017
“Independent of all complicating issues such
as logistics and cost, the national
implementation of low-dose CT screening is
simply not hitting a nerve for its value as a
public health service.”
— James Mulshine, MD
Effects of volume CT lung cancer screening
Mortality results of the NELSON randomised-
controlled population-based screening trial
Harry J. de Koning, MD PhD
PI NELSON
Professor & Deputy Head
Department of Public Health
Erasmus MC, University Medical Center Rotterdam, the Netherlands
H.J. de Koning, C. van der Aalst, P.A. de Jong, E.T. Scholten, K.
Nackaerts, M. Heuvelmans, J-W. Lammers, W.P. Mali, C. Weenink, A.U.
Yousaf-Khan, N. Horeweg, S. v. ’t Westeinde, M. Prokop, J.G.J.V. Aerts,
M.A. den Bakker, E.F. Blom, F.B. Thunnissen, J. Verschakelen, R.
Vliegenthart, J.E. Walter, K. ten Haaf, H.J.M. Groen, M. Oudkerk
&
NELSON-investigatorsNEderlands-Leuvens Longkanker Screenings ONderzoek
Erasmus MC, University Medical Center Rotterdam, University Medical Center Utrecht, Spaarne Gasthuis Haarlem, University Medical Center Groningen,
University Hospital Leuven, Belgium, Maasstad Hospital Rotterdam, University Medical Center Amsterdam, Radboud University Medical Center Nijmegen
Harry J. de Koning, Erasmus MC, Public Health Rotterdam
NELSON - trial ISRCTN 63545820
• Randomized Controlled Trial
• Recruitment through population-based registries
• CT screening vs. no screening
• Different screening intervals
• Volume & Volume Doubling Time of nodules
• Central reading of CT images
• Expert causes of death committee &
• Follow up through national registries
Trial, initially powered (80%) for high risk males, to detect a lung cancer mortality reduction
of ≥ 25% at 10 years after randomization (individual FU)
And includes a small subgroup of women (16%)
Harry J. de Koning, Erasmus MC, Public Health Rotterdam
Harry J. de Koning, Erasmus MC, Public Health Rotterdam
Mailing 2- general health questionnaire- information brochure- invitation to participate- informed consent form
Mailing 1- general health questionnaire
Recruitment step 1:
Men and women aged 50-74 years derived from population registries
n=606,409
Returned questionnaires n=150,920
Completed questionnaires n=148,730
Inclusion Criteria- aged 50-74 years- smoking history >10 cig/day for >30 yrs >15 cig/day for >25yrs- smoking cessation ≤10 yearsExclusion Criteria- A moderate or poor self-reported health who were unable to climb two flights of stairs- weight ≥140 kilogram- lung cancer diagnosis (<5 years ago or ≥5 years ago but still under treatment)- current or past renal cancer, breast cancer or melanoma- CT chest examination <1 year ago
Recruitment step 2:
Eligiblesn=30,959
Initial randomization(1:1)
Eligibles who signed the informed consent
n=15,822
RANDOMISEDn=15,792
Deceased between signing informed consent and randomisation
(based on later linkages with national registries)
n=30
Control Armn=7,892
No screening
Screen Armn=7,900
CT screening in year 1,2,4 and 6.5
(2007)
J Thorac Oncol 2018;13(suppl):Abstr PL02.05
Harry J. de Koning, Erasmus MC, Public Health Rotterdam
Harry J. de Koning, Erasmus MC, Public Health Rotterdam
Year 1 Year 2 Year 4 Year 6.5 Year 10
Control armn=7,892
Screen armn=7,900
95.6% 92.3% 87.6% 66.8%
uptake uptakeuptake uptake
n=7,557 n=7,295 n=6,922 n=5,279
Usual care (no screening)
MORTALITY
ANALYSES
CT screening CT screening CT screening CT screening
NATIONAL LINKAGES- Statistics Netherlands/ Belgium- Dutch/ Belgium Cancer Registry- Centre for Genealogy
CAUSE OF DEATH REVIEW
Year 1 Year 2 Year 4 Year 6.5 Year 10
Control armn=7,892
Screen armn=7,900
95.6% 92.3% 87.6% 66.8%
uptake uptakeuptake uptake
n=7,557 n=7,295 n=6,922 n=5,279
Usual care (no screening)
MORTALITY
ANALYSES
CT screening CT screening CT screening CT screening
NATIONAL LINKAGES- Statistics Netherlands/ Belgium- Dutch/ Belgium Cancer Registry- Centre for Genealogy
CAUSE OF DEATH REVIEW
Harry J. de Koning, Erasmus MC, Public Health Rotterdam
Harry J. de Koning, Erasmus MC, Public Health Rotterdam
Harry J. de Koning, Erasmus MC, Public Health Rotterdam
Yousaf-Khan et al., in preparation
J Thorac Oncol 2018;13(suppl):Abstr PL02.05
Cumulative lung cancer deaths (men only)
Cu
mu
lative
lu
ng
ca
nce
r d
ea
ths
Years since randomisation
50
100
150
200
250
01 2 3 4 5 6 107 8 9
Control arm:
214 lung cancer deaths
Screen arm:
157 lung cancer deaths
Harry J. de Koning, Erasmus MC, Public Health Rotterdam
Lung cancer
mortality
rate ratio
(95% CI)
Year 8 Year 9 Year 10
MALES
0.75
P=0.015
(0.59-0.95)
0.76
P=0.012
(0.60-0.95)
0.74
P=0.003
(0.60-0.91)
FEMALES
0.39
P=0.0037
(0.18-0.78)
0.47
P=0.0069
(0.25-0.84)
0.61
P=0.0543
(0.35-1.04)
Harry J. de Koning, Erasmus MC, Public Health Rotterdam
Rand: 23-12-2003 – 06-07-2006
FU: 23-12-2003 – 31-12-2015
FU 94% complete
year 10
NELSON Volume CT screening
• MALES at high risk for lung cancer have a reduced risk of dying from lung cancer of 26% in the
screen arm compared to the male control arm (95% CI 9-40%)
• In WOMEN, reductions are consistently more favourable: 39-61%
• These results are more favourable than the NLST-results & suggest gender differences
• Volume CT lung cancer screening of high risk former and current smokers results in low referral
rates (2.3%), and a very substantial reduction in lung cancer mortality (in both genders)
Harry J. de Koning, Erasmus MC, Public Health Rotterdam
LUNG CANCER SCREENING-EUROPE
www.ersnet.org/the-society/news/european-respiratory-society-welcomes-the-positive-results-of-nelson-trial
Lung cancer screening-Europe
ERS Seminar 11-12 dec 2018
Lung Cancer Screening: from Trial to Practice
• Target group by age and smoking history
• Former smokers vs active smokers (others: COPD,occupation,..)
• Who selects the screening population?
• Who performs LDCT screening (Mobile CT?)
• Informed decision making: harms & benefits
• Role for GPs; patient advocacy groups
• Smoking cessation program to be offered
• Risk assessment scores/Risk models (PLCOM2012;Bach;LLPv2)
• Blood biomarkers (blood, breath, CT)
Lung cancer screening-Europe
ERS Seminar 11-12 dec 2018
Lung Cancer Screening: from Trial to Practice (2)
• Impact for radiologists:
– Training, LC prediction models; AI software; Radiomics; Central reading?
– Extrapulmonary findings
– Patient communication
• Impact for thoracic surgeons
– ESTS recommendation
– ‘Nodule Board’ (next to MOC)
• Cost-effectiveness
• Pilot study
Seijo LM et al J Thorac Oncol 2018
Brain K et al Thorax 2017
Balata H et al NHS Manchester 2018
Balata H et al NHS Manchester 2018
Lung cancer screening-Belgium
www.stopdarmkanker.be/blog/darmkankerscreening-voor-vlaanderen-een-stapj/
(LUNG) Cancer screening-Belgium
https://www.ccref.org/
https://www.bevolkingsonderzoek.be/
Lung cancer screening-Flanders
• Who organizes?
• Who performs screening?
The Flemish government* itself organises population-based
screening programs but may also grant approval for high-quality
population screening programs initiated by other organisations.
The Flemish working group on Population-wide screening
programs (21 experts)** gives advice on this matter.
Without formal approval population-based screening is not allowed.
www.zorg-en-gezondheid.be/bevolkingsonderzoek
www.zorg-en-gezondheid.be/sites/default/files/atoms/files/BVO%20WG%20samenstelling%202014%20MB.pdf
Lung cancer screening-Flanders
Centres for ‘Kankeropsporing’ (CvKO) – field work
The Centre for ‘Kankeropsporing’ (‘screening’) is a non-profit
organisation, raised November 13, 2012. This Centre offers its
expertise to the Flemish population-based screening programs.
This non-profit organisation was created out of the Consortium of
approved regional screening centres within the Flemish Community
The Centre for ‘Kankeropsporing’ consists of 5 regional sites.
https://www.zorg-en-gezondheid.be/https://www.cvko.vlaanderen/
Lung cancer screening-Flanders
Population-based screening requires a population-wide approach
A well-preplanned population-based screening program is composed of
several quality-proven steps, like
1/ Every participant of the target group is well informed about the harms and
benefits? [Harms & benefits]
2/ The screening method used is well chosen and there isn’t any other approach
more useful than screening? [LDCT; smoking cessation]
3/ Is the target group (very) well-defined? [age & smoking history]
4/ Is it clear for all involved within the screening program, what the real costs are for
the screening and for the diagnosis and treatment of the disease? [Cost benefit
analysis]
5/ Does society (RIZIV) agree with the eventual total costs of screening (societal
acceptance)? [other screening programs]
6/ Are all relevant parties involved in the organisation of the screening? [CvKO]
7/ Are the screening results being adequately registered (with respect for privacy
rules), in order that the effects and the quality of the screening program may be
evaluable? [Centrale Databank/Link met Kankerregister of CT reports, FU, …]https://www.zorg-en-gezondheid.be/bevolkingsonderzoek
Lung cancer screening-Flanders
Population-based screening requires a population-wide approach
When the disadvantages weigh out the advantages and when the
quality of all different steps of this population-based screening cannot
be fully guaranteed, it would be better NOT to organize that particular
population-wide screening.
All these measures are often neglected or only partially covered by the
organizers of a population-wide screening program [creating Task
Force]
https://www.zorg-en-gezondheid.be/bevolkingsonderzoek
Lung cancer screening-Flanders
Lung Cancer Screening Task Force
- Group of interested parties* in lung cancer screening
- To submit a complete (lung cancer screening) report to the
Flemish working group on Population-based screening within the
Flemish Ministery
- Is planned for Q1 2019
- Several planned meetings, to create a full report regarding the
population-based organisation of lung cancer screening with
low-dose chest CT, using the predefined criteria
- Participants*: different parties, e.g. pneumologists, thoracic
surgeons, radiologists, members of the CvKO, epidemiologists,
health economist, …
Financing costs for LD€T screening?
• N cigarettes/day N packs/day smoked
• 1 eurocent/pack cigarettes sold, for “LC screening” ?
• In Belgium: ±625.000.000 packs sold per year (data 2010)
• Total of euros for LC screening: 6.250.000 euro per year
Documentatie map ROKEN
OIVO 2011
With the combined results of the NLST and the NELSON trial, there can no longer be any doubt about the fact that lungcancer screening saves lives. More than 220,000 people are diagnosed with lung cancer annually in the United States, andthe majority have advanced stage III or IV disease. Globally, more than 2 million cases were diagnosed in 2018, with more than 1.7 million deaths. A reduction of lung cancer mortalityby 20% to 30% would be a huge accomplishment in reducingthe global burden of lung cancer.
Nasser Altorki, MD ©Weill Cornell Medical College
ASCO Post, March 10, 2019
VRAGEN?