1

Advances in Internal MedicineAdvances in Internal MedicineLUNG CANCERLUNG CANCER

What’s old, what’s new, and what to What’s old, what’s new, and what to expectexpect

Thierry M. Jahan, M.D.,Thierry M. Jahan, M.D.,Thoracic Oncology ProgramThoracic Oncology Program

UCSF Helen Diller Family Comprehensive UCSF Helen Diller Family Comprehensive Cancer CenterCancer Center

Objectives

• Recognize the changing epidemiology of lung cancer

• Understand the treatment options for early and advanced disease

• Recognize the role of targeted agents and their toxicities

• Recognize the heterogeneity of lung cancer and tumor biology based individualized treatments

• EPIDEMIOLOGY

Jemal, CA Cancer J Clin 2008; 58: 71

Cancer Incidence Deaths

Colon 108,070 49,960

Breast 184,450 40,930

Prostate 186,320 28,660

Total 478,840 119,550

NSCLC Epidemiology

LungLung 215,020215,020 161,840161,840

Statistics for 2008

2

Prototypical U.S. Lung Cancer patient 1950’s-60’s

• 60-70 Year Old Males

• Long Smoking History

• Large Squamous Cell Tumors

• Cowboy Image• Started in 1950s

The Changing Face of Lung Cancer in the U.S.

Annual Age-adjusted Cancer Death Rates, US 1930-2002

Men Women

1987

Etiology Smoking and lung cancer incidence

3

Etiology:Environmental causes

� Smoking:� Tars, tobacco, aromatic amines, Polycyclic aromatic

hydrocarbons

� Environmental:� Second hand smoke, radon

� Occupational:– Asbestos, uranium, beryllium, vinyl chloride, nickel chromates,

coal products, mustard gas, chloromethyl ethers, gasoline , diesel exhaust

Smoking cessation and mortality in women

Nurses Health Study• 104,519 subjects• Lung CA OR Current smokers 21.87(17.85-26.80)

– Past smokers 4.93 (4.00-6.08)

Kenfield, JAMA 2008; 299: 2037

Effect of smoking cessationLung cancer mortality: 21%↓ first 5 yrs

87% ↓ 20-30yrs93% ↓ ≥ 30 yrs

All cause mortality: Level of non-smoker 20yrs

Lung cancer in never smokers

• Women are more likely than men to have non-smoking related cancer

• Incidence rates/100,000:• Women 15-20 Men 4-13.7

• Higher frequency of adenocarcinoma

Wakelee et al, J Clin Oncol, 2007; 25: 472

Gender differences and risk of lung cancer (LC) with smoking

• OR LC in smokers : women 1.2-1.7 times higher than men when adjusted for tobacco dose exposure

• RR for LC in smokers: women 27.9 and men 9.6

Zang, JNCI 1996;88:183

Risch, Am J Epi, 1993;138:281

Schoenberg, Am J Epi 1989;130:688

4

Gender differences in biology

�CYP and GSTM 1 (glutahtione S-transferases) :2 enzyme systems for the metabolism of PAH and intermediate products of tobacco smoke.

�CYP1A1 *2A and *2B assoc with inc risk of LC (OR 4.7 CI 1.2-19)�GSTTI null phenotype OR 1.2 (CI1.0-1.6)

F –OR 3.0 (1.09-8.4) M – OR 1.4 (.5-4.0)

�Higher levels of DNA adducts

Taioli, Int J Epi 2003;32:60

Tang, Carcinogensis, 1998;19:1949

Gender differences in biology

• Hormones and lung cancer• Estrogen receptors are present in lung tumors• Estradiol promotes growth of lung tumors in

preclinical models• Conflicting reports on the influence of hormones

on development of LC in case control and cohort studies

• HRT adversely affects treatment outcomes (MS 79 vs 39 mo p=0.02)

Dubey , Lancet Oncol, 2006, 7:416Ganti, JCO 2005,24:59

SCREENING

National Cancer Institute: SEER Cancer Statistics Review, 1975National Cancer Institute: SEER Cancer Statistics Review, 1975--2001.2001.

Stage IV36%

Unstaged8%

Stage III37%

Stage Stage I/III/II

16%16%

Lung Cancer Stage Distribution at Time of Diagnosis

5

Screening

• IELCAP (Early Lung Cancer Action Program)

• 31,567 H/O tobacco use, second hand , occupational exposure, radon.

• Baseline and annual CT screening• 5500 Positive results requiring further w/u• 535 required biopsy• Lung cancer detected in 484 (1.6%) of which 85%

stage I.

NEJM 2006, 357, 17

Screening

• NLST (National lung screening trial)• Randomized comparison of CT and CXR

• 50,000 enrolled and closed to accrual• Enpoint: survival• Results expected ~ 2009

TREATMENT

Principles of Cancer Therapy

• Diagnosis

• Stage

• Medical condition (performance status, co-morbid diseases)

6

Performance statusKarnofsky Scale Zubrod Scale

Normal, no evidence of disease 100 Able to perform normal activity with only minor 90 symptoms

Normal activity 0

Normal activity with effort, some symptoms 80Able to care for self but unable to do 70normal activities

Symptomatic and ambulatory 1

Cares for self

Requires occasional assistance, cares for 60most needs Requires considerable assistance 50

Ambulatory >50% of time 2

Occasional assistance

Disabled, requires special assistance 40

Severely disabled 30

Ambulatory ≤50% of the time 3

Nursing care needed

Very sick, requires active supportive 20treatment Moribund 10

Bedridden 4

Treatment of NSCLC

• Practically 3 groups:

Local : stage I, II, some IIIA → surgery

adjuvant chemotherapy

Regional: some IIIA, IIIB, → RT ± chemo

Metastatic: Systemic Rx (cytotoxics and targeted agents)

• Early NSCLC

Evolution In Approach To SurgeryOpen or Closed: Does Size Matter?

Thoracotomy Thoracoscopy

7

Surgery

• Advances in surgery:• Videoscopic Assisted Thoracoscopic

Surgery• Speciality training• Shorter hospital stay• Earlier recovery

NSCLC: 5-year Survival by Stage

Stage TMN 5-yr Survival Rates

IA T1NOMO ~70%

IB T2NOMO ~60%

IIA T1N1MO 55%

IIBT2N1MO

T3N0MO~40%

IIIAT1-3N2MO

T3N1M0~25%

IIIB Any T4,N3, MO <5%

IV Any M1 1%

Adapted from Mountain and Dressler. Chest. 1997;111:1718-1723.

Systemic therapy for a local disease ???

• Adjuvant chemotherapy

• Neoadjuvant chemotherapy

�Elimination of micrometastases

�Reduction of recurrence

�Improvement of survival

Adjuvant Chemotherapy

Negative

Trials

Study Stage Chemo 5yrS %

E3590 II and IIIA TRT VS

TRT/CDDP+E

42

38

ALPI I-IIIA Obs

Vs MVP

44

48

Positive

Trials

IALT IB-IIIB CDDP based

Obs

44.5

40.4

NCIC BR10 IB-IIB CDDP + Vin

Obs

69

54

ANITA IB-IIIA Cis/Vin 52

42

JLCRG IA/IB

IB

UFT Vs obs 88 vs 85

85 vs 73

CALGB IB Carboplatin+ P

Obs

59

57(4yrS)

8

5yr OS �15%

MST 73 mo vs 94 mo

Winton ASCO 2004, N Engl J Med 2005; 352:2589-2597 Overall survival - ITT population

Months

Su

rviv

al D

istr

ibu

tion

Fu

nct

ion

1.00

0.75

0.50

0.25

00 20 40 60 80 100 120

OBS.. NVB + CDDP

Median months 43.8 65.8

5yr S 52% 42%

P-value 0.013

Hazard Ratio 0.79 [0.66 -0.95]

Obs

NVB + CDDP

ANITA Trial

Douillard, ASCO, 2005.7

Adjuvant chemotherapy in the elderly

•• OS for >65 was better with chemo vs obs OS for >65 was better with chemo vs obs

HR 0.61 (CI 0.38HR 0.61 (CI 0.38--0.98) p0.98) p--0.040.04• OS lesser for patients >75 compared to those aged 66-74

HR 1.95 (CI 1.11-3.41, p-0.02)

Pepe et al , ASCO 2006, 24: Abstract # 7009

Early Lung cancerWhat’s new?

Good Performance Status

Should be offered to >65 yrs

Those over the age of 75 require further study

� VATS procedures can reduce surgical morbidity

�Adjuvant chemotherapy is the Standard of Care for resected NSCLC

9

• Advanced disease

Progress in the Treatment of Advanced NSCLC:

Baby steps

Median survival

One year survival

Two year survival

Supportive care 4-6 months 10% -

“Older” chemotherapy 6 months 20% ?

“Newer” chemotherapy

8 - 12 months

30% -50%

10%

164,000

56,000

30,00041,000

$1,811

$4,982

$11,233

$14,756

0

20,000

40,000

60,000

80,000

100,000

120,000

140,000

160,000

180,000

Lung Colorecta l Prostate Breast

Sources: American Cancer Society, Cancer Facts and Figures 2005NCI Factsheet, Cancer Research Funding, 2005

Ann

ual U

.S. D

eath

s, 2

005

$0

$2,000

$4,000

$6,000

$8,000

$10,000

$12,000

$14,000

$16,000

National Research Priorities for Lung Cancer"It's the Same Old Song"

NC

I Research D

ollars Per S

ite, 2005

10

• Treatment of advanced diseaseCytotoxic chemotherapyTargeted agents

NonNon--small Cell Lung Cancer Collaborative Group. small Cell Lung Cancer Collaborative Group. BMJ.BMJ. 1995;311:8991995;311:899--909.909.

NSCLC - Chemotherapy

Supportive care plus Supportive care plus cisplatincisplatin--based regimensbased regimens

Supportive careSupportive care

PercentagePercentageSurvivalSurvival

6060

100100

Time From Randomization (months)Time From Randomization (months)66 1212 1818 2424

0000

2020

7070

3030

9090

5050

8080

4040

1010

•• P P =.09, in favor of chemotherapy=.09, in favor of chemotherapy•• HR 0.73HR 0.73

Platinum Chemotherapy Versus Supportive Care in NSCLC

First line chemotherapy for NSCLC

Schiller et al. NEJM 2002;346:92

MS 7.9mo 1yrS 33%

0 5 10 15 20 25 30

Months

0.0

0.2

0.4

0.6

0.8

1.0

Survival by Treatment GroupAll Randomized Cases

Cis/PaclitaxelCis/GemcitabineCis/DocetaxelCarbo/Paclitaxel

0 5 10 15 20 25 30

Months

0.0

0.2

0.4

0.6

0.8

1.0

Survival by Treatment GroupAll Randomized Cases

Cis/PaclitaxelCis/GemcitabineCis/DocetaxelCarbo/Paclitaxel

65 yr old male with lung cancer and good PS progresses after 4 cycles of carboplatin

and paclitaxel. What would you recommend?

2 mo r e

c y cl e s

o f sa m

e c .. .

D i ff e r e

n t si n g l

e a ge n t

c y .. .

S i ng l e

a g en t t

a r ge t e

d t .. .

R ef e r

t o ho s p

i c e

0%

17%

65%

17%

1. 2 more cycles of same chemo just in case more is better

2. Different single agent cytotoxic chemotherapy

3. Single agent targeted therapy4. Refer to hospice

11

Response(%)Median survival (months)

1-year-survival (%)

Docetaxel 75 mg/m2 (n=55)Best supportive care (n=49)

0 3 6 9 12 15 18 21

Cumulative probability

0.0

0.2

0.4

0.6

0.8

1.0

Doc 67.5 37

BSC

4.612

p=0.03

Survival time (months)

Relapsed disease

�QOL with Docetaxel

Shepherd, J Clin Oncol 2000, 18:2095

Second Line TherapyPemetrexed vs. Docetaxel

Pemetrexed (n=283) Docetaxel (n=288)

Sur

viva

l Dis

trib

utio

n F

unct

ion

Months

0.00

0.25

0.50

0.75

1.00

0.0 2.5 5.0 7.5 10.0 12.5 15.0 17.5 20.0 22.5

MST 8.3 mos1-yr OS: 29.7%

HR 0.99

95% CI of HR (0.82, 1.20)

MST 7.9 mos1-yr OS: 29.7%

Hanna JCO, 2004,22:1589

Single agents used in second line therapy

JCO 2004,

18:3722

Single agents used in second line therapy

12

• Treatment of advanced diseaseCytotoxic chemotherapyTargeted therapy

“Normalizing” Tumor Vasculature withAnti-angiogenic Therapy

R.K. Jain. Nat Med 7:987, 2001R.K. Jain. Nat Med 7:987, 2001

“Pruning” of abnormal immature vessels with chemo. Results in better delivery of therapeutics

Ultimately results in blood supply unable to support tumor growth

Bevacizumab Blocks Angiogenesis

Recombinant humanized monoclonal antibody to VEGF-A

13

E4599. Ph III RCT :Bevacizumab and CP vs CP in non-squamous NSCLC

RANDOMIZE

Paclitaxel 200 mg/m 2 IV + Carboplatin AUC 6 IV q 3 wk

X6 cycles

Paclitaxel 200 mg/m2 IV + Carboplatin AUC 6 IV q 3 wk

X6 cyclesBevacizumab 15mg/kg q3 wk til PD

Stratification by:

• Stage (IIIB or IV)

• Geographic regionSandler. NEJM 2006; 355: 2542

IIIB and IV non-squamous

No brain mets

No hemoptysis

No prior chemotherapy

Sandler, ASCO annual meeting, 2005,LBA4

Bevacizumab related toxicity

PC PCB

Gr 4/5 Neutropenia

Hypertension

16.4%

0.7

24%

6%

Gr ¾ Thromboembolism

3% 3.8%*

Hemorrhage 1% 4%

Rx related deaths 2 9 (5 due to hemoptysis)

* p=NS

Epidermal Growth Factor Receptor (EGFR)

Baselga. Eur J Cancer 2001;37 Suppl 4:S16-S22.

14

Tyrosine Kinase Inhibitors

Gefitinib EGFR NSCLCErlotinib EGFR NSCLCImatinib PDGF/C-kit/Bcr-Abl CML,GISTSunitinib VEGF, PDGF, CKIT, RET RCC, GISTCI1033 Pan ERBB (irreversible)GW572016 EGFR/ErbB-2EKB 569 EGFRPTK 787 VEGF, PDGFAMG 706 VEGF PDGF CKIT RET

TGFαTGFα

TKI TKI

Erlotinib (Tarceva)- Phase III BR 21

ECOG PS 1,2,3Prior 1-2 regimens

Erlotinib 150 mg/d Placebo 150 mg/d

Stratification

PS : 0/1 vs 2/3

Prior chemo: 1 vs 2

Prior response to chemo: CR vs PR vs SDShepherd et al, NEJM, 2005, 353:123

Shepherd et al. ASCO 2004 # 7022

Radiographic responses to erlotinib can be dramatic and sustained

15

Significant Clinical predictors to response

Overall response %

P value

Gender Male

Female

6

14

0.006

Histology Adenoca

Other

14

4

<0.001

Ethnic group Asian

Other

19

7.5

0.02

Smoking status Current or ever

Never

12

23

<0.001

Toxicities of EGFR -TKIs

• Acneiform rash 60%• Diarrhea 50%• Transaminitis• Anorexia• Wt loss• Interstitial lung

disease <2%

Rx: moisturizing lotionssun screentopical steroids, clindamycin, Doxycycline

Sur

viva

l dis

trib

utio

n fu

nctio

n

Months

Grade 2/3 (n=17)

Grade 1 (n=26)

No rash (n=14)

Median survival (95% CI)

No rash 1.5 (1–2.2) Grade 1 8.5 (4.8–14.8) p<0.0001*

Grade 2/3 19.6 (10.8–22.1+) p<0.0001*

0 5 10 15 20 25 30

1.00

0.75

0.50

0.25

0.00

*vs no rash

Pérez-Soler R, et al. Lung Cancer 2003;41(Suppl. 2): S246 (Abs. P-611)

Erlotinib

Survival by rash

• SPECIAL POPULATIONS• The elderly

16

Age in Lung CancerRelationship to Prognosis ?????

• MSKCC (JCO 4:1604, 1986)

• ECOG (JCO 4:702, 1986)

• ECOG (JCO 23:175,2005)

– prognosis not related to age– Elderly experience more toxicities

• SWOG (JCO 1991;9:1618)

– Elderly – favorable survival

Randomized Trial of Vinorelbine vs. BSC in the Elderly

The ELVIS Trial

R

A

N

D

O

M

I

Z

E

N

MS

1 yr Survival

QOL

Better

Vinorelbine 80 28 wks 32%

BSC 81 21 wks. 14%

Gridelli, Oncologist 2001;6(S1) 4-7

Chemo-naive

>70 yrs

Treatment in advanced disease

• Conclusions• Multiple cytotoxic chemotherapy available• Options also include targeted agents • Treatment is associated with prolongation

of survival and improved symptoms• Treatment choice is dependent on

performance status, co-morbidities

Treatment in advanced disease

• Conclusions• Be aware of toxicities of targeted agents• Age is not a discriminator in treatment

decisions . Elderly “fit” should be offered anti-cancer treatments.

17

Individualized therapy - Genomic predictors?

Potential Biomarkers for Lung Cancer Treatment

• Platinum – ERCC1• Taxanes – BRCA1• Gemcitabine – RRM1• Pemetrexed – TS expression• Gene expression• EGFR – EGFR mutation, FISH• VEGF - ??

Excision Repair Cross Complementing-1 Enzyme

(ERCC1)

• Involved in DNA repair after damage from cisplatin

• High levels of DNA repair enzyme are linked to cisplatin resistance

4781121161194224355991120163202

0%

20%

40%

60%

80%

100%

0 1 2 3 4 5YearsNo at riskChemotherapy

Control

Control

Chemotherapy

Ove

rall

Sur

viva

l

Adjusted HR=0.65, 95%CI [0.50Adjusted HR=0.65, 95%CI [0.50--0.86], p = 0.0020.86], p = 0.002

Effect of adjuvant chemotherapy on survival in Effect of adjuvant chemotherapy on survival in patients with patients with ERCC1 negative tumorsERCC1 negative tumors

Effect of adjuvant chemotherapy on survival in Effect of adjuvant chemotherapy on survival in patients with patients with ERCC1 negative tumorsERCC1 negative tumors

Soria, ASCO 2006, Abstr # 7010IALT study

18

Adjusted HR=1.14, 95%CI [0.84Adjusted HR=1.14, 95%CI [0.84--1.55], P = 0.401.55], P = 0.40

346285121147165336996127149170

0%

20%

40%

60%

80%

100%

0 1 2 3 4 5YearsNo at risk

ChemotherapyControl

Ove

rall

Sur

viva

lControl

Chemotherapy

Effect of adjuvant chemotherapy on survival in Effect of adjuvant chemotherapy on survival in patients with patients with ERCC1 positive tumorsERCC1 positive tumors

Effect of adjuvant chemotherapy on survival in Effect of adjuvant chemotherapy on survival in patients with patients with ERCC1 positive tumorsERCC1 positive tumors

Soria, ASCO 2006, Abstr # 7010IALT study

Lung cancer - What have we learned?

• Early disease: Adjuvant chemotherapy improves survival

• Advanced disease: Systemic therapy improves survival and QOL

Lung cancer - What have we learned?

• Recognize the unique toxicity profile oftargeted agents

• Biomarkers will provide the platform for

personalized treatment

• Have I missed anything?

19

• Back up slides

Lung Metagene Prognosis

A. Potti, ASCO, 2006, Abstr # 7026

Future Plan

Incorporate LMP into prospective clinical trials of

adjuvant chemotherapy

Biomarker Selection for EGFR Inhibitors:

GGCGGGCCAAACTGCTGGGTGCG

EGFR protein expression by immunohistochemistry

EGFR gene copy number by FISH

EGFR Mutational status

Structure of the EGFR-ATP Binding Site

Red: deletionsLight blue: missense mutationsDark blue: gefitinib

From: Lynch TJ et al. N Engl J Med. 2004;350:2129-2139.

Exons 18, 19, 20 and 21- Tyrosine kinase domain

In frame deletions and missense mutations

20

EGFR mutation and response

RR % OS

EGFR WT

EGFR MT

10

46 p=0.005

No significant difference

Bell, JCO 2005,23:8081

FISH predicts benefit of EGFR-TKIs

Log-rank: p=0.008HR=0.44 (0.23, 0.82)

Log-rank: p=0.59HR=0.85 (0.48, 1.51)

ISEL FISH + BR21 FISH +

Cox: p=0.07HR=0.61 (0.36, 1.04)

BR21 FISH -

0.0

0.2

0.4

0.6

0.8

1.0

0 4 8 12 16

Gefitinib Placebo

Proportionsurviving

Time (months)

ISEL FISH -

Cox: p=0.42 HR=1.16 (0.81, 1.64)

Time (months)

0.0

0.2

0.4

0.6

0.8

1.0

0 6 12 18 3024

Erlotinib Placebo

0.0

0.2

0.4

0.6

0.8

1.0

0 4 8 12 16

Gefitinib Placebo

Proportionsurviving

Time (months) Time (months)

0.0

0.2

0.4

0.6

0.8

1.0

0 6 12 18 3024

Erlotinib Placebo

Biomarkers

• Conclusions

• EGFR biomarkers: Gene copy number predicts response and survival to EGFR-TKIs.

Mutation predicts response but not improved survival

• Ongoing and planned biomarker trials will evaluate biomarker based treatment approach

Lung cancer - What have we learnt?

• Early disease: Adjuvant chemotherapy improves survival

• Locally advanced disease: Combined chemoradiation improves survival

• Advanced disease: Systemic therapy improves survival and QOL

• Biomarkers will provide the platform for personalized treatment

21

• Thank youN=83Unresectable

stage IIIB NSCLC

Gandara et al. 2006, Clin Lung Ca; 8;116..

Docetaxel(75-100 mg/m2)

q3wfor 3 cycles

Concurrent Chemoradiotherapy → Consolidation Docetaxel in Unresectable

Stage IIIB NSCLC: SWOG 9504

Cisplatin(50 mg/m2 on days 1, 8, 29, 36) +

Etoposide(50 mg/m2 on days 1-5, 29-33) +

Radiotherapy(61 Gy chest [1.8-2.0 Gy/d])

starting on day 1

MS 26mo 5yrS 29%

• Is maintenance therapy required after consolidation docetaxel?

Gefitinib maintenance in inoperable IIIA/ IIIB NSCLC

SWOG 0023

Cisplatin50 mg/2 d 1,8,29,36

Etoposide50mg/m2 d1-5, 29-33

XRT 1.8- 2 Gy/d 61 Gy

DOCETAXEL75 mg/m2x 3 cycles

1o Endpoint: Overall Survival; 20 Endpoint: PFS, toxicity and correlative

PLACEBO

GEFITINIB500 mg/day250 mg/day

RANDOMIZE

Kelly et al. ASCO, 2007, Abstr# 7513.

22

Abstract # 7513Abstract # 7513Overall Survival Overall Survival

0%

20%

40%

60%

80%

100%

0 12 24 36 48 60Months After RANDOMIZATION

Gefitinb

Placebo

N

118

125

Events

71

54

Median

in Months

23

35

P = .01

1 YROS

2 YR OS

73% 46%

59%81%

Median FU time:27 months

Causes of Death by Treatment Arm

Parameter

Gefitinib

%

Placebo

%

Alive 47 71

Dead 71 54

Cancer 61 43

Toxicity 2 0

Other Causes 1 3

Unknown 7 8

N=83Unresectable stage IIIB NSCLC

Gandara et al. 2006, Clin Lung Ca; 8;116..

Docetaxel(75-100 mg/m2)

q3wfor 3 cycles

Is even consolidation docetaxel required?

Cisplatin(50 mg/m2 on days 1, 8, 29, 36) +

Etoposide(50 mg/m2 on days 1-5, 29-33) +

Radiotherapy(61 Gy chest [1.8-2.0 Gy/d])

starting on day 1

MS 26mo 5yrS 29%

Unresectable stage IIIA/B

NSCLC

Hanna et al, Proc ASCO 2007, Abstr# 7512

Docetaxel(75-100 mg/m2)

q3wfor 3 cycles

Concurrent chemo/RT with or without consolidation docetaxel

Cisplatin(50 mg/m2 on days 1, 8, 29, 36)

Etoposide(50 mg/m2 on days 1-5, 29-33)

Radiotherapy(59.4 Gy chest) starting on day 1

Observation

N=73

N=74

1° Endpoint: Overall Survival

23

Months since registration

0 10 20 30 40 50 60

Per

cent

of p

atie

nts

surv

ivin

g

0%

25%

50%

75%

100%

ObservationDocetaxel Consolidation

Abstract # 7512Overall Survival

Observation: 3yr S 27.6%Docetaxel: 3yr S 27.2%

P-value: 0.940

Unresectable stage III NSCLC

• Concurrent chemoradiotherapy• Is superior to sequential chemo-radiotherapy• Should be offered to eligible candidates.

• Consolidation or maintenance therapy• Does not improve OS

• Associated with increased toxicity

• Should not be routinely used

Goldstraw P et al. J Thorac Oncol. 2007;2:706-714.

Staging – Proposed changes

6th Edition T/M and Descriptor

Proposed T/M

T1 (≤ 2 cm) T1a

T1 (2 – 3 cm) T1b

T2 (≤ 5 cm) T2a

T2 (5 – 7 cm) T2b

T2 (> 7 cm) T3

T3 invasion T3

T4 (same lobe nodules) T3

T4 (extension) T4

M1 (ipsilateral lung) T4

T4 (pleural dissemination) M1a

M1 (contralateral lung) M1a

M1 (distant) M1b