Tumori del polmone. Dati epidemiologici, prevenzione e diagnostica
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!