Early Detection of Lung Cancer

Cancer and new technologies: a future bet

Madrid July 2013
Dr. Nir Peled (MD, PhD) Thoracic Cancer Research and Detection Center
Tel HashomerTel-Aviv University
Peled.nir@gmail.com +972-528-556767
http://medicine.mytau.org/peled/

Respiratory System Organization

The Components
of the Respiratory
System
Figure 15-1

Respiratory System Organization

The Bronchial
Tree

Figure 15-6(a)

Respiratory System Organization

Alveolar
Organization

Figure 15-7(c)

Cancer incidence and mortality

BACKGROUND
FIGURE 1 Ten Leading Cancer Types for Estimated New
Cancer Cases and Deaths, by Sex, United States, 2009

Lung Cancer Chain of Changes

Normal

Dysplasia

Hyperplasia

Metaplasia

Carcinoma in situ

Carcinoma

STAGE I

Primary tumor in the lung

No lymph nodes involved.

STAGE II

Primary tumor in the lung and lymph nodes

within the lobe or hilum.

STAGE III

Locally advanced disease.

Mediastinal LN.
Primary tumor invades local structures (spine, etc).

STAGE IV
Cancer spread to the other lung or outside the
chest.
Pleural effusion.

Lung Cancer: Outcome

Overall 5 YS: 15 %
Early recognized disease: 5 YS 49 %
Stage
I
II
IIIa
IIIb
IV

5-Year Survival
60-80%
40-50%
25-30%
5-10%
<1%

Diagnostic Techiques
Trans Thoracic Biopsy (Under CT)
Bronchoscopy
Mediastinoscopy
Surgery

BRONCHOSCOPY

CHEST RADIOGRAPH

Other Biomarkers
Sputum for Cytology
Circulating Tumor Cells
Circulating Blood Markers/Profiles
Proteins
mRNAs
DNA

Auto-Antibodies
Imagine (CT/CT-PET/Cxray)

A lung-cancer cell imaged with the

Cell-CT and visualized in three
different modes

Left: 2D image imitating the view through a microscope. Note the two nuclei and the spotty chromatin.
Center: The same cell in 3D in nuclear surface view.
Right: A slice is taken through the center of the nucleus, exposing tubular extensions of the nuclear envelope--invisible in 2D.
The nucleoli are labeled in red. Scale bars = 3 m

Dr. Nir Peled (MD, PhD) Tel Aviv Univesity

NLST (N=53,000); Annual LDCT X 3

Lung Cancer Case Survival

Table 11.5.3d

True and False Positive Screens by

Screening Round and Trial Arm
CT

Total positives

With lung cancer

Without lung
cancer

CXR

Round
1
N (%)

Round
2
N (%)

Roun
d3
N (%)

Roun
d1
N (%)

Roun
d2
N (%)

Roun
d3
N (%)

7,193
(100)

6,902
(100)

4,054
(100)

2,387
(100)

1,482
(100)

1,175
(100)

270 (4)
6,923
(96)

168 (2)
6,734
(98)

211
(5)
3,843
(95)

136
(6)
2,251
(94)

65 (4)
1,417
(96)

78 (7)
1,097
(93)

96% of the positive LDCTs were false

positive.

Which statement proves that

cancer screening saves lives?
More cancers are detected in screened
populations then in unscreened populations.
Screen-detected cancers have better 5-year
survival rates then cancers detected because of
symptoms.
Mortality rates are lower among screened
persons then unscreened in RCT

From: Do Physicians Understand Cancer Screening Statistics? A National Survey of Primary Care Physicians
in the United States
Ann Intern Med. 2012;156(5):340-349. doi:10.7326/0003-4819-156-5-201203060-00005

Figure 3. Physicians' understanding of which screening statistics provide evidence that screening saves lives.

Date of download:
8/17/2012

Copyright The American College of Physicians.

All rights reserved.

Wegwarth O et al. Ann Intern Med 2012;156:340-349

2012 by American College of Physicians

CT Screen Study Participant (DM)

7/22/99
3 X 3 mm RUL nodule

7/10/00
increased
6 X 6 mm

7/18/01
increased
11 X 6 mm
IA NSCLC

CT Screen Study Participant

2/15/00
3 X 3 mm RUL nodule
new from 9/21/99
F/U 6 mos
Courtesy D Midthun

8/15/00
perhaps slightly larger
than on 2/15/00
F/U 3 mos

11/17/00
further increased in size
1.3 X 0.7 X 0.5 mm

SCREENING METHODOLOGY

symptoms

detection
undetectable

a
s
s
e
s
s
R m
i e

Guidelines for CT Management of Small

Pulmonary Nodules
Statement from the Fleischner Society
size (mm)

low risk
patient

high risk
patient

<4
> 4-6
> 6-8
>8

no f/u

CT 12 m*

12 m*

6-12 m & 18-24 m*

6-12 m & 18-24 m*

3-6m, 9-12 m, 24m*

3, 9 & 24m*,
dynamic CT, PET bx

# new CT nodule in person 35 years of age or older

* CT f/u; stop if no change at end of f/u exams listed
MacMahon et al. Radiology 2005;237:395-400

LDCT Randomized Trials

DANTE
DLCT
ITALUNG

NLST
* Ongoing,
99% complete

NELSON *
15,822

Garg
Depiscan

LSS

53,454

Cumulative Numbers of Lung Cancers and of Deaths from

Lung Cancer.

The National Lung Screening Trial Research Team. N

Engl J Med 2011. DOI: 10.1056/NEJMoa1102873

What we dont know

Who should undergo CT screening?
Does everyone included in NLST benefit?
(NLST 10 yr risk varies from 2%-20%; average
~10%)

For entire cohort:

20% in Lung Ca deaths
Are risk models accurate enough to base an
extrapolation on?
Average 10 yr risk: ~10%
2%

55 y.o, quit
15 yrs ago

74 y.o, still
smokes 3 ppd

20%

What about other risk factors

family history, previously curatively treated
Less(i.e.
(or no?)
Greaterlung
cancer, etc.)?
Benefit?
Benefit?

The Proposed Protocol

High Risk for
Lung Cancer

SPN on LDCT

Normal LDCT

Annual FollowUp
Tissue Diagnoses

Non Invasive
Approach

Low Probability for Ca.

High Probability for Ca.

Non-Invasive
Follow-up

Tissue Diagnoses

SPN study
Age (years)
Active Smokers
Never Smokers
PY (Total)
Nodule Existence
Nodule Size (cm)
Histology

Stage

Benign Nodules
(N=29)
61.5 6.4
10 (35%)
3 (10%)
44.3 33.3
21 (72%)
1.861.1
Non-Cancerous
13
Dysplasia/Hyperplasia
9
Infectious/Inflammation
5
Carcinoid
2

Malignant Nodules
(N=53)
64.9 7.2
19 (36%)
8 (15%)
40.5 27.0
53/53 (100%)
2.71.7
NSCLC:
47
Adenocarcinoma
30
Squamous
13
Large Cell
2
Poorly Diff.
2
SCLC
6
NSCLC:
Stage I / II
Stage III / IV
SCLC:
Limited / Ext

23 / 4
10 / 10
3 / 3

P-value
(<0.05)
NS
NS
NS
NS
NS

Discrimination between Benign* and Malignant Nodules

Malignant/ Benign
SCLC/NSCLC

Sensitivity

Specificity

Accuracy

PPV

NPV

76.2-87.9

83.3-88.2

78.8-88.0

88.9-93.5

66.7-78.9

75

96.56

93.93

96.6

75.0

Peled N et al. Journal Thoracic Oncology, 2012

Lab members

Nir Peled, MD PhD, FCCP

PI

Maya Ilouze, PhD

Post-Doc

Meital Elimelech, MSc

Clinical coordinator

Ronen Shavit, MD student Yossi Tzur, MD student Ori Liran, MD student

Chetz Project
Chetz Project
Chetz Project

Inbar Nardi-Agmon,
MD student

Tali Fienberg, MSc

PhD student

Tami Rashal, MD

Sheba Medical Center, Tel-Aviv University

nirp@post.tau.ac.il ;
Marina Pekar,
MD student

Tina Wexler, MD student

Chetz Project

+972 3 5307028

Contact Information
Nir Peled, MD PhD FCCP
Head, Thoracic Cancer Research and Detection
Center.
Sheba Medical Center, Tel-Aviv University
nirp@post.tau.ac.il
+972-3 5307028

Dr. Nir Peled (MD, PhD) Tel Aviv Univesity