1. NON-SMALL CELL
LUNG CANCER
ALEXANDER DRILON MD
Fellow, Thoracic Oncology Service
Memorial Sloan Kettering Cancer Center
The following material is intended for MSKCC internal medicine housestaff teaching purposes only.
The slides are courtesy of Dr. Alexander Drillon and were updated for the LibGuide in 2011-2012.

2. Leading cause of cancer
death
• 85% of patients will die of disease
• 2x lung CA vs. breast CA deaths
(more than breast + colon)
• 70% late stage at diagnosis
• early stage: high recurrence rates

3. history

4. “Of all the cancers, tobacco-associated lung cancers are the
ones which most unequivocally reflect a conflict
between biological evolution and the social ratchet of
pleasurable behavior and commercial gain.”
Mel Greaves
Cancer, The Evolutionary Legacy

5. 20th Century Epidemic
• 20 year latency period
• Cigarettes manufactured
1910
• Increased incidence in
men in 1930s
• Incidence in women
increased only in 1960s
after WW2

8. Doll and Hill: British Doctors Study
causal relationship established in the 1950s  1964 Surgeon General’s Warning

9. etiology

10. Smoking accounts for 90%
of all lung cancers
• ten years to reduce risk
by 75%

11. Relative Risk of Developing Lung Cancer
35
30
25
20
15
10
5
0
Smoking + Smoking Passive Smoke Asbestos Radon
Asbestos

12. lung CA
screening

14. 31K patients
484 patients diagnosed with CA
85% with Stage I lung CA
Stage I survival was 88% at 10 years
vs. Historical standard of 70% at
5 years

15. lead time
length
time

16. overdiagnosis bias

17. • POPULATION:
• age 55 to 74
• heavy smoker or former smoker (quit within last
15 years)
• no prior cancer within past 5 years
• 53K patients randomized to CXR vs. low
dose helical CT scan  annual imaging x 3

18. 20%
reduction in
lung cancer
mortality
7%
reduction
in all cause
mortality

19. • 3% of scans led to diagnosis of
lung CA, NNS 288
• high false-positive screening
rate in both arms (96% with CT
and 95% with CXR)

21. NSCLC
histology

22. Adenocarcinoma
Most common histology (40%)
• Least associated with smoking, but
majority who get it have been exposed
to cigarette smoke (70%)
• More common in women
Location
• peripheral, scar tissue
Presentation
• frequently metastatic disease
• hypertrophic
osteoarthropathy, Trosseau’s
• BAC: multiple pulmonary nodules

23. Squamous Cell
• Second most common(30%)
• most common histology until 1987
• 90% associated with cigarette smoking
• P63 characteristic IHC marker
• Presentation
• centrally located mass
• PTHrP: hypercalcemia

24. Large Cell
• Least common subtype (11%)
• associated with gynecomastia
• advances in histopathologic technique: reclassification of
undifferentiated large cell tumors to adenoCA or SCC

25. staging
NSCLC

26. Stage I Stage II
1-5 cm 5-7 cm
1-7 cm

27. Stage IIIa Stage IIIb

28. Stage IV

29. International System for Staging
Percent Surviving at 5 Years
Stage Clinical Stage Pathologic Stage
IA 50 73
IB 43 58
IIA 36 46
IIB 25 36
IIIA 19 24
IIIB 7 9
IV 2 13

30. workup

32. Clinical Staging
• PET/CT chest and upper abdomen, bone scan
• MRI Brain: brain metastases incidence 10-15%

33. Mediastinal
Evaluation
nodes larger than 1 cm
on CT regardless of
FDG uptake

34. Mediastinoscopy

35. Endoscopic Biopsy

36. Transbronchial Biopsy

37. NSCLC
management
surgery

38. NSCLC Management: Stage I and II
Stage Ia SURGERY
Ib
SURGERY CHEMO
Stage IIa
IIb

39. Surgical Approach
Wedge Resection
FVC < 1.5 L

40. Surgical Approach
Lobectomy
FVC at least 1.5 L

41. Surgical Approach
Pneumonectomy
FVC at least 2L

42. Preoperative Evaluation
Stereotactic Body RT
>60 Gy (Timmerman JCO ‘07)

43. NSCLC
management
adjuvant chemo
surgery

44. NSCLC Management: Stage I and II
Stage Ia SURGERY
Ib
SURGERY CHEMO
Stage IIa
IIb

45. RCTs: Adjuvant Chemo
IALT • Cisplatin + Etop/Vinor/Vinblas/Vindes
Le Chevalier • PORT allowed
2003 • Increased DFS, median OS, OS at 5yr by 4%
NCIC • Cisplatin + Vinorelbine
Winston • Median OS from 73  94 months (21 mos)
NEJM 2005 • Increased OS at 5yr by 15%
France • Cisplatin + Vinorelbine
Douilliard • Median OS from 43  65 months (12 mos)
Lancet Onc 2006

46. Meta-Analyses: Adjuvant Chemo
Hotta • Cisplatin-based chemo, Uracil-Tegafur
JCO • N= 5,716
2004 • Increased OS, HR 0.87
• Cisplatin-based chemo
• N=4,500
LACE • Stage IB HR 0.92, Stage II HR 0.83, Stage III HR 0.83
Pignon
JCO 2008

47. Adjuvant Chemotherapy
4 Cycles of Therapy
• Cisplatin + Vinorelbine
SURGERY CHEMO • Cisplatin + Docetaxel
• Cisplatin + Gemcitabine
• Cisplatin + Pemetrexed

48. NSCLC
management
multi
modality
therapy

49. NSCLC Management
sequence of treatments is variable
Stage IIIa CHEMO SURGERY RT
IIIb CHEMORADIATION

50. Stage IIIb
inoperable

51. NSCLC Management
Stage Ia SURGERY
Ib
SURGERY CHEMO
Stage IIa
IIb
Stage IIIa* CHEMO SURGERY RT
IIIb CHEMORADIATION
Stage IV CHEMO

52. NSCLC
management
chemo
therapy

53. Median Overall Survival in Months
14
12
10
8
6
4
2
0

54. Systemic Therapy: Cisplatin Doublet
• Lilenbaum Semin Onc 99
2 drugs >
• Lilenbaum ASCO 02
1 drug • Sederholm Semin Onc 02
• Crimo JCO 99
2 drugs <
• Soguet Ann Onc 02
3 drugs • Greco Cancer 02
• Belani Semin Onc 01
Cisplatin > • Rosell Ann Onc 02
• Ardizonni Meta JNCI 07
Carboplatin • Hotta Meta JCO 04

55. Systemic Therapy: Histology Matters
• PEMETREXED: non-squamous histology
• GEMCITABINE: squamous histology
• PACLITAXEL, VINORELBINE: any histology

56. Systemic Therapy: Maintenance
platinum-
based
therapy Pemetrexed
• Increased PFS, Median OS 10.6  13.4 mos (2.8 mo)
Ciuleneau Lancet 2009
platinum-
based
therapy Erlotinib
• Increased PFS, Median OS 11  12 mos (2 mo)
Cappuzzo Saturn Trial

57. NSCLC
management
targeted
therapy

58. Antiangiogenic Therapy

59. • BEVACIZUMAB
till progression
of disease
• Median OS 10.3
 12.3 mos

60. Epidermal Growth Factor Receptor

63. Increased OS by 13%
HR 0.871
Cetuximab 400mg

64. erlotinib
gefitinib
tyrosine kinase inhibitors

67. http://www.egfr-mutation.com/EGFR-lung-cancer/

68. POPULATION: IIIB or IV adenoCA, never or light smokers, Asian, untreated
RESPONSE RATE (Clinical): gefitinib (43%) vs. chemo (32%)
RESPONSE RATE (EGFR Mutant): gefitinib (71%) vs. chemo (47%)

69. QUALITY OF LIFE: better in gefitinib arm NO DIFF MED OS (about 17 mos)

70. RR 73% vs. 33% PFS 10.8 vs. 5.4 mos p < 0.001

72. PFS 14.6
months
conserved LREA
motif
small in-frame
deletions residues
747-750
point missense
mutation mutation
PFS 9.7
months

73. TKI Sensitivity

74. TKI Resistance

77. EML4-ALK Inhibition

81. crizotinib

85. Lung cancer is NOT one disease.
TISSUE IS THE ISSUE

86. MOLECULAR TREATMENT DELAY
TESTING
and
oncology
oncology result treatment
referral
clinic visit received started
Diagnosis
Adenocarcinoma
oncology oncology MOLECULAR result treatment
biopsy Adenosquamous referral clinic visit TESTING received started
carcinoma
NSCLC-NOS
WEEK 0 1 2 3 4 5

87. LUNG CANCERS
Carcinoid
Large Cell
Large Cell Neuroendocrine
5%

88. thank
you