Hstoria del tratamiento de cáncer del pulmón

History of Lung Cancer

TreatmentMauricio Lema Medina MD

Clínica de Oncología Astorga / Clínica SOMAMedellín

Lung Cancer: A man-made epidemic

Progress Against Lung CancerTobacco

Undurraga P. Rev Chil Enf Respir 2012; 28: 35-50

James Albert Bonsack (1889)- 70.000 cigarettes in 10 hours

“You ask me what it is we need to win this war. I answer tobacco as much as

bullets.” – Black Jack (WWI)

Progress Against Lung CancerTobacco

Progress Against Lung CancerSmoking in the US

Source: National Cancer Institute

Progress Against Lung CancerSmoking in the US

Progress Against Lung Cancer1970–1979

Saracci R. Asbestos and Lung Cancer: An Analysis of the EpidemiologicalEvidence on the Asbestos-Smoking Interaction. Int J Cancer. 1977; 20:323-331

…May be hazardous to your health.


Progress Against Lung CancerPioneers

Richard Doll (1912-2005)


Getting to know your body

Progress Against Lung CancerBronchoscopy


1904

Progress Against Lung CancerBronchoscopy


1904

Progress Against Lung CancerFlexible bronchoscopy


1966

Progress Against Lung CancerTechnology


Sir Godfrey HounsfieldCT (EMI) Scanner-1972-Nobel Prize 1979

Progress Against Lung Cancer2000–Present

Sharples LD, Jackson C, Wheaton E, et al. Clinical effectiveness and cost-effectiveness of endobronchial and endoscopic ultrasound relative to surgical staging in potentially resectable lung cancer: results from the ASTER randomised controlled trial. Health Technol Assess. 2012; 16: 1-4.

Surgery: a glimpse of hope


Evarts A. Graham

Progress Against Lung CancerPneumonectomy

1933

Progress Against Lung CancerPneumonectomy

EA GrahamJL Gimore

Chemotherapy


Cisplatin


Cisplatin


Timmerman R, Paulus R, Galvin J, et al. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA. 2010; 303:1070-1076.



Early-1970s: Radiotherapy included in combined modality treatment trials for SCLC and NSCLCEarly-1970s: Lymph-node mapping introducedEarly-1970s: Sublobular resection found to be adequat por limited-stage lung cancer


Mid-1970s: Chemotherapy combinations prove effective in small cell lung cancer

1974: First data-driven revision of TNM classification of lung cancer

1974: ACTH research identified SCLC as an ectopic hormone-producing tumor





1986: Second-hand smoke formally declared a carcinogen


1987: Scientists discover key genetic vulnerability in tumor cells – EGFR





1990–1992: Combining chemotherapy and radiation prolongs survival for non-small cell lung cancer


1993: Simultaneous radiation and chemotherapy boosts survival for small cell lung cancer


Mid-1990s: New generation of chemotherapy drugs for non-small cell lung cancer


1995: Analysis affirms benefits of chemotherapy for advanced non-small cell lung cancer



1996: Topotecan approved as second round of treatment for small cell lung cancer

1998: PORT increases mortality in NSCLC



1999: Cranial radiation reduces risk of small cell lung cancer spreading to the brain1999: Simultaneous chemotherapy and radiation proven most effective for stage III non-small cell lung cancer1999: Giving radiation to the chest twice-daily increases survival for small cell lung cancer




Sandler A et al. N Engl J Med 2006;355:2542-2550.

Kaplan–Meier Estimates of Overall Survival (Panel A) and Progression-free Survival (Panel B).


Timmerman R, Paulus R, Galvin J, et al. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA. 2010; 303:1070-1076.



2000: Study links household radon exposure to lung cancer2000: Second round of chemotherapy boosts survival in advanced non-small cell lung cancer


2003: First targeted drug approved for non-small cell lung cancer


2004: Studies show that specific EGFR mutations are associated with response to gefitinib2004: FDA approves second targeted drug, erlotinib, for non-small cell lung cancer2004–2005: Adjuvant therapy proven effective in lung cancer


2005: Anti-angiogenic drug bevacizumab extends survival for advanced lung cancer2005: New project to map lung cancer genome


2008: Circulating tumor cells in the blood can help track treatment response in select patients


2009: Maintenance therapy improves survival for advanced non-small cell lung cancer

C/P vs C/G in Advanced NSCLC: OS by Histology

Survival Time (Mos) in All PatientsWith Squamous Histology

Surv

ival

Pro

babi

lity

SquamousNonsquamous

Survival Time (Mos) in PatientsWith Nonsquamous Histology

Surv

ival

Pro

babi

lity

Scagliotti GV, et al. J Clin Oncol. 2008;26:3543-3551.

C/PC/G

C/P vs C/G

Median Survival11.8 mos10.4 mosAdjusted HR: 0.81(95% CI: 0.70-0.94)

C/PC/G

C/P vs C/G

Median Survival9.4 mos10.8 mosAdjusted HR: 1.23(95% CI: 1.00-1.51)

1.00.90.80.70.60.50.40.30.20.1

0300 6 12 18 24

1.00.90.80.70.60.50.40.30.20.1

0300 6 12 18 24


2010: Older patients should be considered for the same aggressive chemotherapy as younger patients2010: Adding palliative care to standard chemotherapy improves survival for advanced lung cancer patients2010: New lung cancer staging system is adopted2010: Drug aimed at a newly identified target causes dramatic tumor shrinkages2010: CT scanning reduces lung cancer deaths among heavy smokers

Survival Pem + Cb + Bev Pac + Cb + BevMedian OS, mos 12.6 13.4HR (95% CI; P value) 1.00 (0.86-1.16; P = .949)

Survival rate, % 1 yr 52.7 54.1 2 yr 24.4 21.2

Patel J, et al. 2012 Chicago Multidisciplinary Symposium in Thoracic Oncology. Abstract LBPL1.

PointBreak: OS From Randomization (ITT)

Censoring rate for Pem + Cb + Bev: 27.8%; Pac + Cb + Bev: 27.2%

0 3 6 9 12 15 18 21 24 27 30 33 36 390

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Mos From Induction

Surv

ival

Pro

babi

lity

Pem + Cb + BevPac + Cb + Bev

Lung Cancer Screening

The National Lung Screening Trial Research Team . N Engl J Med 2011;365:395-409.

Cumulative Numbers of Lung Cancers and of Deaths from Lung Cancer.

National Lung Screening Trial: Survival Curves

Relative reduction in all-cause mortality of 6.7% (P = .02)

1877 deaths in LDCT group, 2000 in CXR group

Lung CancerMortality

All Mortality

National Lung Screening Trial Research Team, et al. N Engl J Med. 2011;365:395-409.

0 1 2 3 4 5 6 7 8

1.000.990.980.970.960.950.940.930.920.910.90

CT arm lung cancerCXR arm lung cancer

CT arm all-causeCXR arm all-cause

Prob

abili

ty o

f Sur

viva

l: A

ll Pa

rtic

ipan

ts

Yrs From Randomization

Progress Against Lung CancerFive-Year Survival

11

12

13

14

15

16

17

18

19

1975

1977

1979

1981

1983

1985

1987

1989

1991

1993

1995

1997

1999

2001

2003

2005

2007

2009

Year of Diagnosis

% o

f Pat

ient

s S

urvi

ving

Fiv

e Y

ears


Progress Against Lung CancerMortality

32

37

42

47

52

57

62

1970

1972

1974

1976

1978

1980

1982

1984

1986

1988

1990

1992

1994

1996

1998

2000

2002

2004

2006

2008

2010

Year of Death

Can

cer D

eath

s pe

r 100

,000

Peo

ple


Progress Against Lung CancerNew Cases

46

51

56

61

66

71

1973

1975

1977

1979

1981

1983

1985

1987

1989

1991

1993

1995

1997

1999

2001

2003

2005

2007

2009

Year of Diagnosis

New

Can

cer C

ases

per

100

,000

Peo

ple


Conclusions• Lung cancer therapy

– Surgery may cure some– RT may prolong OS in some

• Cure even less– Metastatic disease

• Dismal prognosis for most patients• Selected patients may have a hope

– Tobacco cessation / screening / targeted therapy and Immunotherapy MAY hold the key

Health & Medicine

Hstoria del tratamiento de cáncer del pulmón