Transcript Update on Molecular Biology of Lung Cancer

Lung Cancer in 2011
Dr. Natasha Leighl, MD MMSc FRCPC
Medical Oncologist, Princess Margaret Hospital
Assistant Professor, Medicine, University of Toronto
Lung Cancer: a growing problem
• One of the most common cancers in Canadians, and the
leading cause of cancer deaths (27%)
• 1.4 million new cases per year, 1.2 million deaths
• Most present with advanced disease, severe symptoms
• North American incidence falling in men, rising in women
• Peak incidence in 70s
• Most ex-smokers, about 30% smokers, 15% nonsmokers
Estimated new cases in Canada, 2011
Prostate
25,500
Colon
22,200
Breast
23,600
Lung
25,300
Canadian Cancer Statistics 2011
Estimated cancer deaths, Canada 2011
5 yr OS
Prostate
4,100 95%
Colon
8,900 61%
Breast
5,100 87%
Lung
20,600 18%
0
5000
10000
15000
20000
25000
30000
Canadian Cancer Statistics 2011
Cancer Research Dollars
Research Funding
• 7% of Canadian research dollars go to lung
cancer, less than 1% of donations
• Breast cancer support, services outnumber
lung cancer by more than 10 to 1
• Approximately $23,000 research dollars spent
per breast cancer patient, compared to
$1,800 per lung cancer patient
Causes of Lung Cancer
• SMOKING!!!! (87%)
• Occupational exposure
– Asbestos, arsenic, nickel, petroleum
– Radon, Radiation
• Passive smoking
• Age
• ? Genetic predisposition
• ?Environmental exposures-air pollution
Lung Cancer Types
15%
15%
10%
25%
Bronchial
Pluripotential
Stem Cell
35%
Small Cell
Adenocarcinoma
Squamous Cell
Large Cell
Mixed/Other
15% Small Cell
85% Non-small Cell (NSCLC)
Histological Types of Lung Cancer
Adenocarcinoma
75
Squamous
cell
Percent
50
BAC
Large cell
25
Other
0
1962-1968
Gazdar and Linnoila, Seminars Oncol 1988; 15(3): 215
1972-1978
1963-1988 NCI
T stage
T1 -  3 cm, not in
main bronchus
T stage
T1 -  3 cm, not in
main bronchus
T2 - >3 (<7)cm,2cm
from carina, inv’n
visceral pleura,
subtotal atelectasis
T stage
T1 -  3 cm, not in
main bronchus
T2 - >3 (<7)cm,2 cm
from carina, inv’n
visceral pleura,
subtotal atelectasis
T3 – >7 cm, invade
chest wall, diaphragm,
med pleura, parietal
pericard, total atelect,
satellite nodules same
lobe
T stage
T1 -  3 cm, not in
main bronchus
T2 - >3 (<7)cm,2 cm
from carina, invn
visceral pleura,
subtotal atelectasis
T3 – >7cm, invade
chest wall, diaphragm,
med pleura, parietal
pericard, total atelect,
satellite nod same lobe
T4 – inv med, hrt, grt vessels, trachea, esoph, vert body,
carina, nodules ipsilat lung, malignant pl effusion
N stage
N1 – ipsilateral
peribronchial,
pulmonary nodes
N stage
N1 – ipsilateral
peribronchial,
pulmonary nodes
N2 – ipsilateral
mediastinal,
subcarinal nodes
N stage
N1 – ipsilateral
peribronchial,
pulmonary nodes
N2 – ipsilateral
mediastinal,
subcarinal nodes
N3 – contralateral
med, hilar, any
scalene, supraclav
nodes
M Stage
M1a – nodule in
contralateral lung,
malignant effusion
M1b – distant mets
Common Sites:
Liver
Bone
Brain
Adrenals
Pleura, Pericardium,
Other Lung
Survival by Pathologic Stage
Changes to Staging - 2009
• Current system implemented in 2009
• Key changes from 1996 system:
– Tumors more than 7 cm moving from T2 to T3
– Changing classification of same lobe satellite nodules
from T4 to T3
– Changing ipsilateral lung but different lobe metastases
from M1 to T4, and contralateral lung nodules from M1 to
“M1a”
– Changing malignant effusions from T4 to M1a
Old Clinical
Stage
Current
Clinical
Stage
Old Pathologic
stage
Current Pathologic
Stage
What tests do you need?
• Diagnosis
– Bronchoscopy (>90%) / mediastinoscopy (node),
endobronchial ultrasound (with nodal biopsy, EBUS)
– Needle aspirate or biopsy (>95%), sputum x 3(80% v 20%)
– Video-Assisted Thoracoscopic Surgery (VATS)
– Thoracentesis (pleural effusion)
• Staging
–
–
–
–
–
–
Chest X-ray / CT Scan (Chest + Upper Abdomen)
Mediastinoscopy (assess node involvement), EBUS
Blood counts, chemistry
Bone scan (if indicated)
CT / MRI brain (if indicated)
FDG PET for SPN, resectable, Stage III NSCLC in Ontario
PET for NSCLC
PET image courtesy of Dr Nevin Murray, BC Cancer Agency
PET in NSCLC
• Solitary Pulmonary Nodules
– FNA or biopsy best approach
– Meta-analyses (no RCTs):
– Sensitivity 96-97%, Specificity 78-86%
– False negatives in low grade tumours (e.g.
BAC, GGOs)
– False positives in inflammatory conditions
– So if biopsy not possible, PET uptake + intervene. If negative, follow (CT q3m x 2 y)
PET in NSCLC
• Staging of Primary Lung Cancer
– 11 systematic reviews, 3 RCTs, 22 other studies
– Standard staging +/- PET
• 51% relative reduction in futile thoracotomies in one trial;
no difference in 2nd trial
– PET vs. Standard Staging
• Shorter time to diagnosis (14 days vs. 23)
• Fewer mediastinoscopies, invasive tests to stage med
– Indicated in addition to standard staging for
resectable and stage 3 NSCLC
– In early stage patients upstaged by PET (up to 15%),
should verify results to confirm true positive
PET in SCLC
• Limited evidence in SCLC
• PET accuracy in staging 83-99%
(limited versus extensive stage disease)
• Better to map out primary tumour and
involved nodes, less sensitive for
metastatic disease
• May be helpful tool in radiation planning