Tumori del polmone. Dati epidemiologici, prevenzione e diagnostica

Comments

Transcription

Tumori del polmone. Dati epidemiologici, prevenzione e diagnostica
Tumore del polmone
Dati epidemiologici, prevenzione e diagnostica
Claudia Galassi
Torino 23 ottobre 2015
• Incidenza:
-proporzione di
"nuovi eventi" che si
verificano in una
popolazione in un
dato periodo di tempo
• Prevalenza
– proporzione di
"eventi" presenti in
una popolazione in
un dato momento.
– Dipende dalla
DURATA della
malattia
Distribuzione per età e sesso,
sopravvivenza
LUNG CANCER Incidence (rates per 100,000) by age groups, by sex - Italy
600
500
400
inc male
inc female
300
200
100
0
0-14
15-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75+
Elaborazione su dati GLOBOCAN 2012, IARC - 9.10.2015
LUNG CANCER Mortality (rates x 100.000) by age-groups, by sex - Italy
600
500
400
mort male
mort female
300
200
100
0
0-14
15-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75+
Elaborazione su dati GLOBOCAN 2012, IARC - 9.10.2015
Sopravvivenza relativa (%) a 5 anni dalla diagnosi per periodo di incidenza - Italia
Uomini
Donne
http://www.registri-tumori.it/cms/it/node/3993
Sopravvivenza relativa (%) a 5 anni dalla diagnosi – confronto con Europa
http://www.registri-tumori.it/cms/it/node/3993
Rischio cumulativo di
diagnosi di tumore
10%
Rischio cumulativo di
morte per tumore
10%
http://www.registri-tumori.it/cms/it/node/3993
Rischio cumulativo di
diagnosi di tumore
13%
Rischio cumulativo di
morte per tumore
3%
http://www.registri-tumori.it/cms/it/node/3993
Burden of disease
Leading Causes of Death in 2001
Cause of death in developed
countries
Number of
deaths
Ischaemic heart disease
3,512,000
Cerebrovascular disease
3,346,000
Chronic obstructive pulmonary
disease
1,829,000
Lower respiratory infections
1,180,000
Lung cancer
938,000
Car crash
669,000
Stomach cancer
657,000
Hypertensive heart disease
635,000
Tuberculosis
571,000
Suicide
499,000
http://ucatlas.ucsc.edu/cause.php
Source: WHO World Health Report 2002. Countries grouped by WHO Mortality Stratum, with Developing Countries representing
regions with High and Very High Mortality, and Developed Countries representing regions with Low and Very Low Mortality.
Globocan 2012
Lung cancer incidence
WORLD
Lung cancer has been the most common cancer in the world for several
decades.
There are estimated to be 1.8 million new cases in 2012 (12.9% of the
total).
http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx
ITALY
http://www.registri-tumori.it/cms/it/node/3993
PIEDMONT
1°°
http://www.cpo.it/it/articles/show/stime-dei-tumori-in-piemonte-nel-2015/
ASL Piemonte
http://www.cpo.it/it/articles/show/stime-dei-tumori-in-piemonte-nel-2015/
ASL Piemonte
http://www.cpo.it/it/articles/show/stime-dei-tumori-in-piemonte-nel-2015/
TURIN
Incidenza
2°°
Variabilità geografica
Lung cancer incidence - MEN
Age standardized rate x 100.000
http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx
Lung cancer mortality - MEN
Age standardized rate x 100.000
http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx
Lung cancer incidence - WOMEN
Age standardized rate x 100.000
http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx
Lung cancer mortality - WOMEN
Age standardized rate x 100.000
http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx
Lung cancer prevalence – MEN AND WOMEN
Age standardized rate x 100.000
http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx
Lung cancer incidence and mortality WORLD -
Age standardized rate x 100.000
MEN
Dati da GLOBOCAN 2012, IARC
Cancer
Incidence
Mortality
5-year prevalence
Number (%) ASR (W) Number (%) ASR (W) Number (%) Prop.
1241601 16.8
34.2 1098702 23.6
30.0 1266696 8.3 48.8
Lung
All cancers excl. non-melanoma
7410376 100.0
skin cancer
204.9 4653385 100.0
126.3 15296119 100.0 589.4
Lung cancer incidence and mortality WORLD
WOMEN
- Age standardized rate x 100.000
Dati da GLOBOCAN 2012, IARC
Cancer
Incidence
Mortality
5-year prevalence
Number (%) ASR (W) Number (%) ASR (W) Number (%) Prop.
583100 8.8
13.6 491223 13.8
11.1 626382 3.7 24.1
Lung
All cancers excl. non-melanoma
6657518 100.0
skin cancer
165.2 3548190 100.0
82.9 17159060 100.0 660.5
PIEDMONT
http://www.cpo.it/it/articles/show/stime-dei-tumori-in-piemonte-nel-2015/
Tassi di incidenza (x 100.000) per aree geografiche italiane e sesso (standard Europa)
Tassi di mortalità (x 100.000) per aree geografiche italiane e sesso (standard Europa)
http://www.registri-tumori.it/cms/it/node/3993
Fattori di rischio
3°°
L’Agenzia Internazionale per la ricerca sul cancro (IARC)
stima che, nel mondo, tra l’85% e il 90% dei tumori del
polmone siano causati dal fumo di tabacco, da solo o
in interazione con altri cancerogeni.
Leading Causes of Death in 2001
Cause of death in developed
countries
Number of
deaths
Ischaemic heart disease
3,512,000
Cerebrovascular disease
3,346,000
Chronic obstructive pulmonary
disease
1,829,000
Lower respiratory infections
1,180,000
Lung cancer
938,000
Car crash
669,000
Stomach cancer
657,000
Hypertensive heart disease
635,000
Tuberculosis
571,000
Suicide
499,000
http://ucatlas.ucsc.edu/cause.php
Source: WHO World Health Report 2002. Countries grouped by WHO Mortality Stratum, with Developing Countries representing
regions with High and Very High Mortality, and Developed Countries representing regions with Low and Very Low Mortality.
Because tobacco smoking is such a powerful determinant
of risk, trends in lung cancer incidence and mortality are
a reflection of population-level changes in smoking
behaviour, including dose, duration, and type of tobacco
used.
The geographical and temporal patterns of lung cancer
today largely reflect tobacco consumption dating from
two or three decades back.
Eriksen M, Mackay J, Ross H. (2012). The Tobacco Atlas, Fourth Edition.
Atlanta: American Cancer Society and World Lung Foundation.
L’Agenzia Internazionale per la Ricerca sul
Cancro ha recentemente classificato
l’inquinamento atmosferico esterno come
“cancerogeno per l’uomo” (Gruppo 1;
IARC ottobre 2013)
Per il tumore al polmone sono noti diversi fattori di rischio, il più
forte è il fumo di tabacco.
Quanto forte?
RR* di tumore al polmone per uomini fumatori: 23,3
RR* di tumore al polmone per donne fumatrici: 12,7
RR di tumore al polmone per PM10 (ESCAPE**) 1,22
*
* * ESCAPE: European study of Cohorts for air pollution effects
L’Agenzia Internazionale per la ricerca sul cancro (IARC)
stima che, nel mondo, tra l’85% e il 90% dei tumori del
polmone siano causati dal fumo di tabacco, da solo o
in interazione con altri cancerogeni.
La stessa stima per l’inquinamento atmosferico si aggira
sul 5% (Cohen, 2005).
http://www.registri-tumori.it/cms/it/node/3993
Copyright © 2000, British Medical Journal
DA : Travis W.D., Brambilla E., Muller-Hermelink H.K., Harris C.C. (Eds.): World Health
Organization Classification of Tumours. Pathology and Genetics of Tumours of the Lung,
Pleura, Thymus and Heart. IARC Press: Lyon 2004
http://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb10/index.php
DA : Travis W.D., Brambilla E., Muller-Hermelink H.K., Harris C.C. (Eds.): World Health
Organization Classification of Tumours. Pathology and Genetics of Tumours of the Lung,
Pleura, Thymus and Heart. IARC Press: Lyon 2004
http://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb10/index.php
Variabilità temporale
Because tobacco smoking is such a powerful determinant
of risk, trends in lung cancer incidence and mortality are
a reflection of population-level changes in smoking
behaviour, including dose, duration, and type of tobacco
used.
The geographical and temporal patterns of lung cancer
today largely reflect tobacco consumption dating from
two or three decades back.
DA : Travis W.D., Brambilla E., Muller-Hermelink H.K., Harris C.C. (Eds.): World Health
Organization Classification of Tumours. Pathology and Genetics of Tumours of the Lung,
Pleura, Thymus and Heart. IARC Press: Lyon 2004
http://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb10/index.php
http://www.registri-tumori.it/cms/it/node/3993
http://www.registri-tumori.it/cms/it/node/3993
http://www.registri-tumori.it/cms/it/node/3993
Interventi di prevenzione primaria
4°°
http://www.cpo.it/it/pubblicazioni/show/cessazione-del-fumo-di-tabacco-linee-guida-clinico-organizzative-per-la-regione-piemonte-quaderno-n-3/
http://www.registri-tumori.it/cms/it/node/3993
Diagnostica precoce (screening)
per il tumore al polmone ?
Symptoms
Appear
Death from cancer
Situation 1: Not Screened
Found Early
by Screening
Survival Time
Situation 2
Survival Time
Death
Situation 3
Survival Time
== Lead
Lead Time
Time
= Life Extended
Symptoms
Appear
Death from cancer
Situation 1: Not Screened
Found Early
by Screening
Survival Time
Situation 2
Survival Time
Death
Situation 3
Survival Time
= Lead Time
= Life Extended
Guidance
Criteria for appraising the viability, effectiveness and
appropriateness of a screening programme
Ideally all the following criteria should be met before screening for a condition is
initiated:
1. The condition
1.1. The condition should be an important health problem.
1.2. The epidemiology and natural history of the condition, including development from
latent to declared disease, should be adequately understood and there should be a
detectable risk factor, disease marker, latent period or early symptomatic stage.
1.3. All the cost-effective primary prevention interventions should have been
implemented as far as practicable.
……
https://www.gov.uk/government/publications/evidence-review-criteria-national-screening-programmes/
criteria-for-appraising-the-viability-effectiveness-and-appropriateness-of-a-screening-programme
Published 1 January 2013
Guidance
Criteria for appraising the viability, effectiveness and
appropriateness of a screening programme
2. The test
2.1. There should be a simple, safe, precise and validated screening test.
2.2. The distribution of test values in the target population should be known and a suitable
cut-off level defined and agreed.
2.3. The test should be acceptable to the population.
2.4. There should be an agreed policy on the further diagnostic investigation of individuals
with a positive test result and on the choices available to those individuals.
2.5. If the test is for mutations the criteria used to select the subset of mutations to be
covered by screening, if all possible mutations are not being tested, should be clearly set out.
https://www.gov.uk/government/publications/evidence-review-criteria-national-screening-programmes/
criteria-for-appraising-the-viability-effectiveness-and-appropriateness-of-a-screening-programme
Published 1 January 2013
Guidance
Criteria for appraising the viability, effectiveness and
appropriateness of a screening programme
3. The treatment
3.1. There should be an effective treatment or intervention for patients identified through
early detection, with evidence of early treatment leading to better outcomes than late
treatment.
3.2. There should be agreed evidence based policies covering which individuals should be
offered treatment and the appropriate treatment to be offered.
3.3. Clinical management of the condition and patient outcomes should be optimised in all
health care providers prior to participation in a screening programme.
https://www.gov.uk/government/publications/evidence-review-criteria-national-screening-programmes/
criteria-for-appraising-the-viability-effectiveness-and-appropriateness-of-a-screening-programme
Published 1 January 2013
Guidance
Criteria for appraising the viability, effectiveness and
appropriateness of a screening programme
4. The screening programme
4.1. There should be evidence from high quality Randomised Controlled Trials that the screening
programme is effective in reducing mortality or morbidity. ….
4.2. There should be evidence that the complete screening programme (test, diagnostic
procedures, treatment/ intervention) is clinically, socially and ethically acceptable to health
professionals and the public.
4.3. The benefit from the screening programme should outweigh the physical and psychological
harm (caused by the test, diagnostic procedures and treatment).
https://www.gov.uk/government/publications/evidence-review-criteria-national-screening-programmes/
criteria-for-appraising-the-viability-effectiveness-and-appropriateness-of-a-screening-programme
Published 1 January 2013
Guidance
Criteria for appraising the viability, effectiveness and
appropriateness of a screening programme
4. The screening programme
4.4. The opportunity cost of the screening programme (including testing, diagnosis and
treatment, administration, training and quality assurance) should be economically
balanced in relation to expenditure on medical care as a whole (ie. value for money).
Assessment against this criteria should have regard to evidence from cost benefit and/or
cost effectiveness analyses and have regard to the effective use of available resource.
4.5. All other options for managing the condition should have been considered (eg.
improving treatment, providing other services), to ensure that no more cost effective
intervention could be introduced or current interventions increased within the resources
available.
https://www.gov.uk/government/publications/evidence-review-criteria-national-screening-programmes/
criteria-for-appraising-the-viability-effectiveness-and-appropriateness-of-a-screening-programme
Published 1 January 2013
Guidance
Criteria for appraising the viability, effectiveness and
appropriateness of a screening programme
4. The screening programme
4.6. There should be a plan for managing and monitoring the screening programme and
an agreed set of quality assurance standards.
4.7. Adequate staffing and facilities for testing, diagnosis, treatment and programme
management should be available prior to the commencement of the screening
programme.
4.8. Evidence-based information, explaining the consequences of testing, investigation
and treatment, should be made available to potential participants to assist them in
making an informed choice.
4.9. Public pressure for widening the eligibility criteria for reducing the screening interval,
and for increasing the sensitivity of the testing process, should be anticipated. Decisions
about these parameters should be scientifically justifiable to the public.
https://www.gov.uk/government/publications/evidence-review-criteria-national-screening-programmes/
criteria-for-appraising-the-viability-effectiveness-and-appropriateness-of-a-screening-programme
Published 1 January 2013
Un esempio di cosa NON
dovrebbe mai accadere
Caratteristiche dei tumori della prostata
Il tumore della prostata NON è una singola malattia con un
comportamento uniforme, ma
piuttosto un “insieme” di malattie, che includono:
- tumori a crescita molto lenta, che non causeranno
mai sintomi né ridurranno la speranza di vita
- tumori aggressivi, che crescono molto velocemente
- forme intermedie (alcuni tumori possono anche cambiare
le caratteristiche nel tempo)
6
2
Sovra diagnosi
= diagnosi eccessive perché inutili
= diagnosi di tumori che non causeranno
mai sintomi né ridurranno la speranza di vita
Lo screening aumenta la probabilità di trovare
tumori (anche quelli “silenti”)
Sovra trattamento
I trattamenti successivi espongono gli uomini
ai possibili effetti collaterali
6
4
Stima dei danni e benefici dello
screening con PSA, in una ipotetica
popolazione di 1000 uomini di 55-69
anni di età,
seguita per 10 anni.
Sulla base dei dati degli studi
disponibili (2012)
1000 uomini sottoposti a screening.
Di questi:
100-120
Avranno risultati falsi positivi, che potranno causare ansia e portare alla biopsia
Gli effetti avversi della biopsia includono infezioni, dolore, sanguinamento
110
avranno una diagnosi di tumore della prostata, e di questi:
• almeno 50
avranno complicanze dei trattamenti, come infezioni, disfunzioni
sessuali, o problemi di continenza urinaria o fecale
•4
Moriranno a causa del tumore della prostata
•1
Eviterà la morte (non morirà) per tumore della prostata
Ipotesi di frequenza dei trattamenti:
60% chirurgia
30% radioterapia
10% osservazione
Annals of Internal Medicine 2012
marzo 2012
The U.S. Preventive Services Task Force
(USPSTF) recommends against prostatespecific antigen (PSA)-based screening for
prostate cancer.
This is a grade D recommendation.
Carcinoma della prostata. Linee Guida clinico organizzative per la Regione
Piemonte, 2009
Per le stesse motivazioni lo screening non dovrebbe essere
proposto a livello individuale.
Diagnostica precoce (screening)
per il tumore al polmone ?
• Studi inclusi
– 8 RCT e 1 CT (Erfurt County)
• Studi esclusi:
– Durata del follow-up minore di 5 anni
• (n. 3: DANTE;DLCST; MILD)
– Studi fattibilità (mortalità non analizzata)
• (n.2: Depiscan Group;Yang 2008)
– Studi ongoing (mortalità non ancora pubblicata)
• (n.3: ITALUNG; LUSI; NELSON 2003).
studio
anni
partecipanti
intervento
controllo
Czech
1976-1982 Men,
40-64
Current
smokers, lifetime
> 150000 cig
semi-annual chest
RX and sputum
cytology
one chest RX and
sputum cytology at
the end of the study
Erfurt
County
1972-1977 Men,
40-65
Smokers and
non-smokers
chest RX at sixmonthly intervals.
chest RX at 18monthly intervals.
Johns
Hopkins
1973-1978 Men,
> 45
Smokers (>= 1
pack/ day)
annual chest RX
and 4-monthly
sputum cytology
annual chest RX
(US) Kaiser
Foundation
1964-1980 M+F,
35-54
Smokers and
non-smokers
encouraged
annual checkup
(chest RX)
not urged but
tollerated
Mayo Lung
Project
1971-1976 M,
> 45
Current smokers
four-monthly chest
RX and sputum
cytology
standard recomm. (1
RX per year)
Mem SloanKettering
1974-1978 M,
> 45
Current smokers
annual chest RX
and 4-monthly
sputum cytology
annual chest RX
North
London
1960-1964 M,
> 40
Smokers and
non-smokers
six-monthly chest
RX
Rx (entry and end)
PLCO
1993-2001 M+F,
55-74
Smokers and
non-smokers
RX baseline and
annual (3 years)
Usual care
http://www.osservatorionazionalescreening.it/sites/default/files/allegati/Screening.pdf
http://www.registri-tumori.it/cms/it/node/3993
•Plain chest radiograph screening has been shown to be ineffective for lung cancer screening.
We recommend not screening for lung cancer with chest radiograph (Grade 1A).
5°°
http://www.uptodate.com/contents/screening-for-lung-cancer
This topic last updated: Aug 03, 2015
Grade 1A recommendation
A Grade 1A recommendation is a strong recommendation, and applies to most
patients in most circumstances without reservation. Clinicians should follow a
strong recommendation unless a clear and compelling rationale for an alternative
approach is present.
Explanation:
A Grade 1 recommendation is a strong recommendation. It means that we believe that if you
follow the recommendation, you will be doing more good than harm for most, if not all of
your patients.
Grade A means that the best estimates of the critical benefits and risks come from consistent
data from well-performed, randomized, controlled trials or overwhelming data of some
other form (eg, well-executed observational studies with very large treatment effects).
Further research is unlikely to have an impact on our confidence in the estimates of benefit
and risk.
http://www.uptodate.com/contents/screening-for-lung-cancer
This topic last updated: Aug 03, 2015
studio
anni
North
American
NLST
2002-2004
partecipanti
M+F,
55-74
history of
cigarette-smoking
of at least 30
pack-years and if
former smokers
had quit within the
previous 15 years
intervento
a total of three
screenings with
low-dose CT at
yearly intervals
controllo
a total of three
screenings with
chest RX at yearly
intervals
Table. Screening Scenarios From CISNET Models*
Benefit
Harm‡
Minimum
PackYears at
Screenin
g, n
Minimum
Age at
Which to
Begin
Screenin
g, y
Time
Since
Last
Cigarette
,y
Populati
on Ever
Screene
d, %
Lung
Cancer
Deaths
Averted,
%
Lung
Cancer
Deaths
Averted,
n
Total CT
Screens,
n
Radiatio
nInduced
Lung
Cancer
Deaths,
n
Overdiag
nosis,%§
§
CT
Screens
per Lung
Cancer
Death
Averted,
n
40
60
25
13.0
11.0
410
171,924
17
11.2
437
40
55
25
13.9
12.3
458
221,606
21
11.1
506
30
60
25
18.8
13.3
495
253,095
21
11.9
534
30
55
15
19.3
14.0
521
286,813
24
9.9
577
20
60
25
24.8
15.4
573
327,024
25
9.8
597
30
55
25
20.4
15.8
588
342,880
25
10.0
609
20
55
25
27.4
17.9
664
455,381
31
10.4
719
10
55
25
36.0
19.4
721
561,744
35
9.5
819
Screening Scenario
Abbreviation: CISNET=Cancer Intervention and Surveillance Modeling Network; CT=computed tomography.
Note: Bolded row highlights the screening scenario with a reasonable balance of benefits and harms and that is recommended by
the USPSTF.
* All scenarios model the results of following a cohort of 100,000 persons from age 45 to 90 years or until death from any cause,
with a varying number of smokers and
former smokers screened on the basis of smoking history, age, and years since stopping smoking.
† For all scenarios, screening is continued through age 80 years.
‡Number of CT screenings is a measure of harm because it relates to the number of patients who will have risk for overdiagnosis
and potential consequences from false-positive results.
§ Percentage of screen-detected cancer that is overdiagnosis; that is, cancer that would not have been diagnosed in the patient's
lifetime without screening.
http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/lung-cancer-screening#Pod9
http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/lung-cancer-screening#Pod9
Response to Public Comments
………
Many comments expressed concerns about implementation of a screening
program, predicting substantially greater harm in the community setting
than was found in the NLST.
….
A section on implementation of a screening program was added,
emphasizing the need for monitoring this implementation, quality assurance
in diagnostic imaging, and appropriate follow-up to replicate the benefits
observed in the NLST in the general population.
http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/lung-cancer-screening#Pod9
Response to Public Comments
……..
Some comments expressed concern about the cost of implementing a screening
Program ….
…..
The USPSTF did not incorporate the costs of a screening program or the potential savings
from a reduction in treatment of advanced lung cancer into the recommendation.
http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/lung-cancer-screening#Pod9
Curl et al. 2015. Understanding Cost-Effectiveness Analyses: An Explanation Using Three Different Analyses of Lung
Cancer Screening. AJR 2015; 205:344–347
http://www.osservatorionazionalescreening.it/sites/default/files/allegati/Screening.pdf
6°°
Response to Public Comments
Some comments expressed concern about ….
… the potential paradoxical effect of enabling persons to continue smoking
with the perception that medical care can mitigate the risks of smoking.
http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/lung-cancer-screening#Pod9
Guidance
Criteria for appraising the viability, effectiveness and
appropriateness of a screening programme
Ideally all the following criteria should be met before screening for a condition is
initiated:
1. The condition
1.1. The condition should be an important health problem.
1.2. The epidemiology and natural history of the condition, including development from
latent to declared disease, should be adequately understood and there should be a
detectable risk factor, disease marker, latent period or early symptomatic stage.
1.3. All the cost-effective primary prevention interventions should have been
implemented as far as practicable.
……
https://www.gov.uk/government/publications/evidence-review-criteria-national-screening-programmes/
criteria-for-appraising-the-viability-effectiveness-and-appropriateness-of-a-screening-programme
Published 1 January 2013
[email protected]
Grazie per l’attenzione!