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.
Source: National Cancer Institute
Progress Against Lung CancerPioneers
Richard Doll (1912-2005)
Progress Against Lung CancerPioneers
Getting to know your body
Progress Against Lung CancerBronchoscopy
Undurraga P. Rev Chil Enf Respir 2012; 28: 35-50
1904
Progress Against Lung CancerBronchoscopy
Undurraga P. Rev Chil Enf Respir 2012; 28: 35-50
1904
Progress Against Lung CancerFlexible bronchoscopy
Undurraga P. Rev Chil Enf Respir 2012; 28: 35-50
1966
Progress Against Lung CancerTechnology
Progress Against Lung CancerPioneers
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
Progress Against Lung CancerPioneers
Evarts A. Graham
Progress Against Lung CancerPneumonectomy
1933
Progress Against Lung CancerPneumonectomy
EA GrahamJL Gimore
Chemotherapy
Progress Against Lung CancerTechnology
Cisplatin
Progress Against Lung CancerTechnology
Cisplatin
Progress Against Lung Cancer1970–Present
Timmerman R, Paulus R, Galvin J, et al. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA. 2010; 303:1070-1076.
Progress Against Lung Cancer1970–1979
Progress Against Lung Cancer1970–1979
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
Progress Against Lung Cancer1970–1979
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
Progress Against Lung Cancer1970–1979
Progress Against Lung Cancer1980–1989
Progress Against Lung Cancer1980–1989
Progress Against Lung Cancer1980–1989
1986: Second-hand smoke formally declared a carcinogen
Progress Against Lung Cancer1980–1989
1987: Scientists discover key genetic vulnerability in tumor cells – EGFR
Progress Against Lung Cancer1990–1999
Progress Against Lung Cancer1990–1999
Progress Against Lung Cancer1990–1999
Progress Against Lung Cancer1990–1999
1990–1992: Combining chemotherapy and radiation prolongs survival for non-small cell lung cancer
Progress Against Lung Cancer1990–1999
1993: Simultaneous radiation and chemotherapy boosts survival for small cell lung cancer
Progress Against Lung Cancer1990–1999
Mid-1990s: New generation of chemotherapy drugs for non-small cell lung cancer
Progress Against Lung Cancer1990–1999
1995: Analysis affirms benefits of chemotherapy for advanced non-small cell lung cancer
Progress Against Lung CancerTechnology
Progress Against Lung Cancer1990–1999
1996: Topotecan approved as second round of treatment for small cell lung cancer
1998: PORT increases mortality in NSCLC
Progress Against Lung CancerTechnology
Progress Against Lung Cancer1990–1999
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
Progress Against Lung Cancer2000–Present
Progress Against Lung CancerPioneers
Progress Against Lung Cancer2000–Present
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).
Progress Against Lung Cancer2000–Present
Timmerman R, Paulus R, Galvin J, et al. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA. 2010; 303:1070-1076.
Progress Against Lung Cancer2000–Present
Progress Against Lung Cancer2000–Present
2000: Study links household radon exposure to lung cancer2000: Second round of chemotherapy boosts survival in advanced non-small cell lung cancer
Progress Against Lung Cancer2000–Present
2003: First targeted drug approved for non-small cell lung cancer
Progress Against Lung Cancer2000–Present
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
Progress Against Lung Cancer2000–Present
2005: Anti-angiogenic drug bevacizumab extends survival for advanced lung cancer2005: New project to map lung cancer genome
Progress Against Lung Cancer2000–Present
2008: Circulating tumor cells in the blood can help track treatment response in select patients
Progress Against Lung Cancer2000–Present
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
Progress Against Lung Cancer2000–Present
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
Source: National Cancer Institute
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
Source: National Cancer Institute
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
Source: National Cancer Institute
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