LUNG CANCER

1. LUNG CANCER- TREATMENT RECENT ADVANCES
& RESULTS
Presenter- Dr.Jyotindra singh
NIMS,HYDERABAD
Non Small Cell Lung Cancer

2. Introduction
• Most common malignancy in males
around the world.
• Leading cause of cancer related
mortality.
• Lung cancer recently surpassed
heart disease as the leading cause
of smoking-related mortality!
• In India accounts for the
commonest cancer in 3 leading
cancer registries – Bhopal, Delhi &
Mumbai.

3. Incidence & Prevalence
Incidence per 100,000
3.8
India
12.1
26.6
China
67.5
13.3
Japan
44.6
12.9
22
120
100
22
80
51.2
60
33.5
40
55.7
Males
Females
Male
Female
2002
2000
1998
1996
1994
1992
1990
0
1988
80
1986
60
1984
40
1982
20
1980
0
20
1978
USA
1976
UK
1974
Sweden

4. Classification &
Pathology

5. Pathology
Primary Lung Cancer
Small Cell type (20% – 30%)
Non Small cell type (70% - 80%)
Bronchial surface epithelial type
Squamous cell (30 - 50%)
Goblet cell type
Adenocarcinoma (20 - 40%)
Clara cell type
Large Cell (10 – 15%)
Type II alveolar cell type
Adenosquamous
Bronchial gland type
Carcinomas with sarcomatous elements
Neuroendocrine
Others

6. Squamous cell carcinoma
Incidence of SCC appears to be
decreasing relative to adenocarcinoma.
• Arise centrally –(two third) within
the main, lobar, segmental or
subsegmental bronchi.
• Grow slow,metastasize late
• Extends both intrabronchially &
peribrionchially.
• Because there is exfoliation of the
malignant cells from the bronchial
surface, squamous cell carcinoma
can be detected by cytologic
examination at its earliest stage.
• Peripherally located-undergo central
necrosis with resultant cavitation

7. Adeno Ca.
SCC

8. Squamous cell carcinoma
• Better prognosis than
adenocarcinoma
• The more necrosis – the
worse the prognosis
• Well differentiated SCC –
more locoregional spread
• Poorly differentiated SCC
– early metastases to
distant sites
• Alveolar filling of
peripheral SCC – more
favorable prognosis
CAVITATTION DUE TO TUMOUR NECROSIS

9. Adenocarcinoma
•
•
•
•
•
•
Adenocarcinoma
Usually arise in the smaller
peripheral airways (as distinct
from the cartilage bearing
bronchi).
Detected earlier by radiology.
Most common in non-smokers
and women.
Rising incidence associated with
different pattern of tobacco
consumption.
More frequently associated with
pleural effusions and distant
metastases.
Premalignant leison is known as
atypical alveolar hyperplasia.

10. Adenocarcinoma
On routine medical examination, the chest film of
a 64-year-old man shows bilateral primary lung
tumours in the upper lobes; the lesion on the left
side is partly obscured by the clavicle. (b) CT scan
clearly defines the irregularly shaped primary
lesions (arrows). Synchronous primary lung cancers
occur in about 3-5% of patients and can be of
different histologic subgroups.

11. PROGNOSTIC FEATURES
•
Scar carcinoma- poor
•
Central fibrosis<5mmexcellent,>15mm – worst
•
Ground glass opacity <3 mm on
HRCT –Better prognosis.
•
Incidence of lymph node
involvement is less or even
absent when greater percentage
of ground glass appearance.
•
•
RET MET
Central tumours- higher incidence
of LN metastasis.
ROS1
EGFR
KRAS
No known
genotype
BAC (variant)- higher incidence of
LN involvement .
ALK
•
Neuroendocrine
differentiation,WDFA –poor
prognosis.
BRAF
HER2
PIK3CA
,

12. Risk Factors
• Smoking
• Genetic predisposition
– Genetic trait : Li Fraumeni syndrome
(P53 mutation)
– Gene polymorphisms:
• DNA repair genes : XRCC1
• COX 2
• Interleukin 6
• Occupational & Environmental
exposure
– Asbestos exposure: Occupational or
residential (silicate type fibers)
– Foundry workers and welders: Ni,
Co, Cd
– Uranium mine workers: Inhaled
Radon
– Air pollution:
• Diesel exhaust
• Metal fumes
• Air sulfate and PAH content
• Dietary influence
– Folate & B12 deficiency
– Inadequate antioxidant consumption
A cigarette is a euphemism for a
cleverly crafted product that
delivers just the right amount of
nicotine to keep its user addicted
for life before killing the person.''
World Health Organization
director-general Gro Harlem
Brundtland

13. Symptoms
Cough
Central growth
Hemoptysis
Dyspnea / Wheeze
Pneumonitis
Symptoms
Pain
Cough
Peripheral growth
Dyspnea
Hoarseness
Lung abscess
Dysphagia
Diaphragmatic palsy
Regional Spread
Horner’s Syndrome
SVC syndrome
Pancoast syndrome

14. Signs
• Signs directly caused by tumor
invasion or compression:
–
–
–
–
–
Limitation of chest movement
Rib tenderness
Vocal cord palsy
Horner’s syndrome
Engorged veins in the chest
wall and face
• Signs due to metastasis
– Bony tenderness
– Adrenal insufficiency
– Organomegaly
SIADH
Cushing’s Syndrome
Carcinoid Syndrome
Gynecomastia
Cerebellar degeneration
Eaton Lambert syndrome
Autonomic neuropathy
Optic neuritis
Pure red cell aplasia
DIC
Anemia, thrombocytopenia
• Paraneoplastic syndromes:
Acanthosis nigricans
– Cancer cachexia (MC)
– Hypercalcemia
– HPOA & clubbing
Hyperkeratosis
Hypertrichosis
VIP induced diarrhea
Hyperamylesmia

15. Investigations
• Investigations to confirm the disease
–
–
–
–
Sputum cytology (sensitivity 65% - 75%)
Transthoracic FNAC (sensitivity 87% - 91%)
Bronchoscopic biopsy (70% - 80%)
TT-FNAC associated with
• Pneumothorax (27%)
• Hemoptysis (5%)
• Local bleeding (11%)
• Investigations to assess the stage
–
–
–
–
Imaging
Bronchoscopy
Mediastinoscopy
VATS
• Investigations to assess fitness for treatment
– Hemogram
– Renal and liver function tests
– Pulmonary function tests

16. Imaging
• Plain X rays
– A tumor visible in a chest X ray has usually completed 75% of
it’s natural history.
– Guides local radiotherapy
• CT scans:
– Accurate assessment of primary disease.
– Best for detection of mediastinal and chest wall invasion.
• Nodal size < 1 cm : 8% chance of occult nodal metastasis
• Nodal size > 2 cm : 70% chance of occult or overt metastasis
– Assessment of abdominal disease esp. of adrenal involvement.
• PET CT has a greater degree of sensitivity for detection of
nodal disease that would be missed by size based criteria
alone.

17. Mediastinal Nodes
EBUS
CT
PET
Sensitivity
92%
76%
80%
Specificity
100%
55%
70%
Accuracy
98%
61%
73%
.

18. Bronchoscopy
Most valuable invasive investigation as it allows:
– Confirmation of diagnosis:
•
•
•
•
Biopsy and brushings 80% accurate
Low false positive rates 0.8%
Transbronchial forceps biopsy positive in 70%
Visualization of tumor done in 60% - 75%
– Staging of the tumor:
• Extent of bronchial and carinal involvement.
– Symptom alleviation:
• Stenting
• Bleeding control
• Importance in brachytherapy
– Response assessment
– Detection of preinvasive malignancy (screening):
• Autoflurosecence bronchoscopy.

19. Staging & Prognosis

20. Staging
• T1:
– 3 cm or less,
completely covered by
pleura, does not involve
main bronchus

21. Staging
• T2:
– > 3cm size.
– Visceral pleura
involved.
– Main bronchus invasion
but > 2cm from carina.
– Atelectasis / obstructive
pneumonitis that
extends to the hilar
region but does not
involve the entire lung.

22. Staging
• T3:
–
–
–
–
–
Chest wall
Diaphragm
Mediastinal pleura
Pericardium
Main bronchus <2cm to
carina
– Complete atelectasis /
obstructive pneumonitis
of entire lung

23. Staging
• T4:
–
–
–
–
–
–
Carina
Vertebrae
Great Vessel
Esophagus
Heart
Separate tumour
nodule in same lobe
– MALIGNANT pleural /
pericardial effusion

24. Staging
• N0:
– No regional LN metastases
• N1:
– LN mets in ipsilateral
peribronchial and/or
intrapulmonary (Levels
10, 11, 12, 13, 14)
• N2:
– Ipsilateral mediastinal or
subcarinal
• N3:
– Contralateral mediastinal
/hilar
– Ipsilateral or contralateral
supraclavicular/ scalene
nodes

25. Staging: AJCC 2002
5 yr overall survival
Stage
TNM
80%
T
N
M
IA
T1
N0
M0
IB
T2
N0
M0
60%
IIA
T1
N1
M0
50%
IIB
T2
N1
M0
T3
N0
M0
T3
N1
M0
30%
T1-T3
N2
M0
20%
T4
N0-N2
M0
IIIA
IIIB
T1-T4
IV
N3
N0-N3
M1
67%
55%
55%
45%
40%
22.50%
10%
7.50%
M0
T1-T4
70%
2.50%
0%
IA
IB IIA IIB IIIA IIIB IV

26. Chart illustrates the descriptors from the 7th edition of the TNM staging system for lung
cancer.
2010;30:1163-1181

27. Staging Controversies
• Tumor size cutoff of 3 cm.
– Several authors have demonstrated the prognostic value of size
> 5 cm and recommend it be incorporated in T3 disease.
• T3N0M0 is lumped into stage IIB
– Prognosis of patients with chest wall disease significantly better
than other T3 category tumors even after complete resection.
– Even those T3 patients who have rib destruction have a
significantly poorer prognosis as compared to those with soft
tissue involvement.
• Normal lymphatic drainage of the lung doesn't obey
the midline!
– Right sided lymphatics extend to the left border of the trachea
across the midline.
– Survival of patients with level 3 and 7 nodal involvement is
markedly poorer.

28. Adverse Prognostic Factors
•
•
•
•
•
•
•
•
Age > 65
Performance status > 2
Advanced stage
Presence of mediastinal lymphadenopathy
Tumor hypercalcemia
Surgical procedure : Limited resection
Positive resection margins
Biological markers:
–
–
–
–
COX 2
p 53
EGFR
erbB2

29. Small cell lung carcinoma
• 15 – 25 % of all lung cancers
• Almost exclusively in smokers
• Distinguished from NSCLC by:
– Rapid doubling time
– High growth fraction
– Early development of widespread metastasis
• Typically arise centrally
• Most common presentation is a large
hilar mass with bulky mediastinal
LAN
• Commonly spread to
liver, adrenals, bone and brain.
• produces paraneoplastic Syndrome.
• Tumour markers-3 main groups:
Neural, Epithelial, Neuroendocrine.

30. VALG STAGING SYSTEM
•
Very-limited disease: confined to one
hemithorax without mediastinal lymph
node involvement.
•
Limited disease: confined to one
hemithorax including the contralateral
lymph nodes (all within radiation field).
•
Extensive disease: beyond these
bounderies.
•
•
•
Very-limited disease~
Limited disease
Extensive disease
5 years
18-24 months
10 months
•
SCLC without treatment
< 3 months

31. PROGNOSTIC FACTORS
•
The host factors of poor
performance status and weight
loss
•
Stage (limited versus extensive).
•
In extensive disease, the number
of organ sites involved is
inversely related to prognosis
•
Metastatic involvement of the
central nervous system, the
marrow, or the liver is
unfavorable compared to other
sites
•
In most trials, women fare better
than men, although the reasons
for this are not known.
•
The presence of paraneoplastic
syndromes is generally
unfavorable

32. LIMITED STAGE
•
Combination of chemo & radiation
•
combination chemotherapy is the
backbone of treatment
•
thoracic radiotherapy significantly
improves long term survival
•
Early thoracic radiotherapy gives better
results than late radiotherapy.
•
Cisplatin and etoposide are most easily
combined within concurrent chemoradiation
protocols (Turrisi et al )
•
BID radiotherapy gives better local control and
better long term survival than QD (5y survival
%: 26% Turrisi et al, NEJM 99 )
•
PCI significantly improves survival by 4-5 % at
5 years when given to complete responders
(Auperin et al )

33. SCLC LD Standard of treatment
Cisplatin 80 mg/m2 d1
Etoposide 120 mg/m2 d1-3
Q3wk x 4
Thoracic Radiotherapy 45 Gy 1.5
Gy/fraction bid 3 wk
Turrisi et al. NEJM 1999

34. EXTENSIVE STAGE DISEASE
• Primary treatment is chemo
•
Cisplatin or Carboplatin plus
Etoposide
– Median survival approx. 11
months
– 5 year survival approx 0%
•
Second line therapy> 95 % relapse
after first-line treatment
•
Topotecan for chemo sensitive
relapse dosease
•
Role of PCI
•
No improvement achieved by
– Novel agents (taxanes, topo 1
inhibitors)
– Biologicals
Topotecan
(n=71)
BSC
(n=70)
HR
(95%CI)
P-value
MS
(weeks)
26
14
0.64
P = 0.0104
6 mo
survival
49%
26%

36. Surgery

37. Surgical Aspects in Lung Cancer
Management
• How fit is the patient ?
• What is the stage,
histology, and exact size
and location ?
• Diagnostic
• Is the patient for
• Treatment
– Diagnosis
– Treatment
– Palliation
–
–
–
–
Bronchoscopy
VATS
Mediasteinoscopy
Mediasteinotomy
– Wedge
– Lobectomy
– Combined wedge
and lobectomy
– Pneumonectomy
• Palliation
– Effusions

38. Surgery : PFT based algorithm
Surgery Type
Lobectomy /Lesser
Pneumonectomy
FEV1 > 1.5 L
FEV1> 60%
DLCO > 60%
FEV1 > 2 L
FEV1> 60%
DLCO > 60%
•V/Q scan
•Calculated Post operative FEV1 & DLCO
Operate
> 40%
< 40%
Exercise study
V02 max < 15 ml/kg/min
Operate
Average risk
V02 max > 15 ml/kg/min
Medically inoperable

39. NSCLC: Stage at Diagnosis
•
Stage I and II
– Surgery as primary treatment
•
Stage III
– Multimodality Therapy
•
III A
– Neoadjuvant therapy
(chemo/radiation) followed by
surgery & additional therapy
III B
– Combination chemotherapy
& radiation therapy.
•
Stage IV
– Palliative chemotherapy and/or
radiation ,best supportive care
Ettinger et al. Oncology. 1996;10:81-111.
Stage I
10%
Stage IV
40%
Stage IIIB
15%
Stage II
20%
Stage IIIA
15%

40. Surgery : Types
• Radical operation:
– Pneumonectomy.
• Lung Conservation:
–
–
–
–
Lobectomy.
Sleeve resection.
Wedge resection.
Segmentectomy.
• Mediastinal lymph node
dissection:
– Provides complete nodal
staging.
– Identifies patients who require
adjuvant radiotherapy.
– Improves survival.
– Improves local control.

41. THORACOTOMY
Posterolateral
Anterolateral
Lateral
Mini
Muscle sparing

42. SEGMNENTECTOMY WEDGE RESECTION
•
Small peripheral tumour confined to
an anatomic segment.
•
Non anatomic and definitive
therapy only in poor risk patients.
•
Patient has limited pulmonary
reserve.
•
CRITERIA FOR WEDGE RESECTION
A tumor < 3cm in diameter
Location in outer third of lung
Absence of endobronchial
extension.
Clear margins by frozen section
negative mediatinal & hilar node
sampling.
•
Low grade tumour under
investigation.
•
•
•
•
Lingulectomy( encompassing 2
segments)- peripheral NSCLC.
•
•
•
LCSG report Ginsberg- limited
resection for T1N0 NSCLC- local
recurrence 3 fold higher than for
lobectomy although ultimate
survival not significantly different,
•
CALBG ( cancer & leukemia
Group B ) - Trial of lobectomy vs
sublobar resection.
•
ACOSOG – Trial sublobar resection
vs sublobar resection + implanted
radiation seeds.

43. Segmentectomy vs wedge rxn
• Segmentectomy
– Better deep margin (El Sharif et al Ann Surg Onc 2007)
– Better nodal evaluation/clearance
• Wedge resection
– Adequate for peripheral (subpleural), small
(1 cm) lesions when margin is wide
(diameter of lesion or more)
– If lesion straddles segmental boundary (i.e.
between lingula and upper division)

44. LOBECTOMY
•
Resection of a lung cancer confined to
parenchyma of a single lobe.
•
Removal of tumour + peripheral
(pleural ) & central lymphatic drainage
pathways
•
Leaves sufficient lung volume to fill the
pleural void.
•
Ginsberg reported operative mortality –
2% vs 4 % for pneumonectomy.
BILOBECTOMY
• Involves resection of right
upper and middle lobe or of
the right middle & lower lobe• when a tumour located in
anterior segement of RUL
•
Tumour in RML has spread
across the minor fissure or
approximates an incomplete
fissure.
• When tumour in RML is centralproximity of the origins of
superior segmental and middle
lobe bronchi
• Interlobar vascular vascular or
nodal involvement.

45. VATS Lobectomy
Absolute containdiactions
• Inability to achieve complete resection
–T3 or T4 tumors
–N2 or N3 disease
• Inability to obtain single lung ventilation
• Large Tumor > 5 cm (too large to remove
through utility incision)
Relative
• Conditions that compromise the safety of
dissection
-- Pre-op chemotherapy / radiation therapy or
both
-- Presence of hilar lympnadenopathy
complicating dissection
-- Presence of extensive adhesions
•
Invasion of extra-pulmonary structure

46. Fewer complications
•
•
1281 Propensity matched patients
(945 VATS, 857 thoracotomy)
Fewer overall complications
(35.7% vs. 26.2% p <.0001)
– Decreased arrhythmias
– Fewer pulmonary complications
– Fewer Blood transfusions
•
•
Shorter Hospital Stay (4 vs. 5
days)
Equal operative mortality (1%)
Hoksch1
Less pain
Walker2
Better quality of life
Sugiura3
Better PFTs
Nakata4
Less pneumonia
Whitson5
Earlier recovery
Demmy6
Easier for octogenarians
McVay7

47. SLEEVE LOBECTOMY
• Resection of lobe along with a
circumferential segment of
mainstem bronchus.
• Indicated for endobronchial
tumours at the origins of right
or upper lobe bronchi.
•
Tumour should be limited to
the lung.
• Pts. With negative mediastinal
node has the best survival.
• Anastomotic complications
Granulations
Stenosis
Bronchovascular fistula

48. Pneumonectomy
•
The indications are central tumors
that involve the main bronchus
•
Large parenchymal cancers that
violate the fissures or invade the
interlobar vessels, or hilar lymph node
involvement.
•
•
•
Pneumonectomy in the latter situation
should be reserved for cases in which
higher stations are benign and a
complete resection is possible.
The operative mortality for
pneumonectomy is about twice that of
lobectomy.
Patients with N2 disease or
centrally locally invasive tumours
are treated by induction therapydue to extent of their disease
they need pneumonectomy
Extended Pneumonectomy
•
Intrapericardial pneumonectomy
•
Supra aortic pneumonectomy
•
Carinal pneumonectomy

49. CHEST WALL INFILTRATION
•
Tumors invading the chest wall are
often resectable.
•
The involved ribs should be
transected several centimeters beyond
the margin of gross involvement.
•
In most cases, one rib and intercostal
tissue above and below the tumor
should also be included in the
resection.
•
For posterior defects, support by the
remaining chest wall muscles and
scapula is usually sufficient.
•
Anterior and lateral defects more
often require reconstruction.
•
For isolated chest wall invasion with
N0 or N1 positive nodes, there is no
known role for neoadjuvant therapy.
•
There is controversy regarding the
necessity of chest wall resection when
invasion is confined to the parietal
pleura.

50. DIAPHRAGM
•
When invasion occurs, that portion of the
diaphragm should be resected with a wide
margin of normal tissue without regard to
the extent of the defect.
•
If the defect is small and can be closed
primarily without tension- Prosthetic
material/muscle flap
•
When a large area of diaphragm has been
resected or when the phrenic nerve has
been resected- diaphragmatic
reconstruction.
•
When the defect is peripheral, it may be
possible to reinsert the remaining cut
edge at a higher level on the chest wall

51. PERICARDIUM
•
Total resection of the pericardium on the
left can be performed without
reconstruction.
•
Partial defects should be closed to
prevent herniation and strangulation of
the left ventricle.
•
On the right side, all pericardial defects,
regardless of size, require repair.
•
Large defects can be closed with the
pericardial fat pad, a pleural flap, or
nonautologous material such as
bovine pericardium or
polytetrafluoroethylene (PTFE).
•
A small opening be left in the repair or
that the prosthetic material be
fenestrated to prevent cardiac
tamponade.

52. VERTEBRA
•
Vertebral body invasion is considered T4
disease and thus unresectable.
•
DeMeester and colleagues described a
technique of partial vertebral resection
for tumors fixed to the paravertebral
fascia.
•
They use a through the transverse
process, costotransverse foramen, and
superficial vertebral body
.
En bloc pulmonary resection and
complete vertebrectomy with
reconstruction by a combined anterior
and posterior approach.
Used when - tumor extent is
completely delineated, nodenegative, totally resectable, and,
after careful evaluation with MRI,
does not involve the spinal canal.

53. Pancoast tumor
•
―Pancoast Tumor‖ is a
neoplasm located at the apical
pleuropulmonary groove
adjacent to the subclavian
vessels.
•
Symptoms arise as a result of
neoplastic involvement of the
brachial plexus, nerve roots,
sympathetic chain, ribs, and
chest wall.
•
Ptosis of the left eyelid, miosis
of the pupil and decreased
sweating of the left face, arm
and upper chest (Horner's
syndrome)
•
chest film- large tumour of the
right upper lobe that has
destroyed the adjacent rib.
•
CT scan reveals rib and soft
tissue involvement as well as
destruction of an adjacent
vertebral body.

54. Preliminary Supraclavicular
Exploration
• Dissection of:
–
–
–
–
–
Posterolateral (Shaw - Paulson)
Anterior cervicothoracic (Dartevelle)
Hemi-clamshell (Burt)
Anteroposterior “hook” (Niwa)
VATS - Posterior
Supraclavicular nodes
S.C. artery
Brachial plexus
Scalene muscles
Phrenic nerve
• Adverse prognostic factors:
– Horner’s syndrome
– N2, N3 disease
– Incomplete resection
• 9% 5yr survival

55. Lymph node dissection
• Lobe specific
mediastinal nodal
dissection in NSCLC:
– Right Side:
• Upper lobe (1,2,3,4,7)
• Middle lobe (1,2,3,4,7)
• Lower lobe (1,2,3,4,7,8,9)
– Left Side:
• Upper lobe (4,5,6,7)
• Lower lobe (4,5,67,8,9)

56. Technique of Mediastinal Lymph Node
Dissection
• Right Paratracheal – clear
all tissue from SVC to
trachea and from upper
lobe bronchus to the
subclavian artery
• Left Aorto-Pulmonary
Window –clear all tissue
from phrenic nerve to the
descending aorta and from
the left upper lobe
bronchus to the subclavian
artery
• Subcarinal- clear out all
tissue bordered by the
right and left bronchi and
pericardium
Video Assisted Mediastinoscopic Lymphadenectomy (VAMLA)

57. Complete Resection
• Free resection margins proved
microscopically
• At least a lobe specific mediastinal
nodal dissection with complete hilar and
intrapulmonary nodal dissection.
• At least 6 nodes should have been
removed with 3 from mediastinal nodes.
• No extracapsular extension in the
nodes.
• Highest mediastinal node removed should
be microscopically free.
Ramon et al Lung Cancer (2005) 49, 25—33

58. Criteria for inoperability
• Tumor based criteria:
–
–
–
–
–
–
–
Cytologically positive effusions.
Vertebral body invasion.
Invasion or in casement of great vessels.
Extensive involvement of Carina or trachea.
Recurrent laryngeal nerve paralysis.
Extensive mediastinal lymph node metastasis.
Extensive N2 or any N3 disease.

59. Patterns of failure
• In stage I tumors:
– Local recurrence rate = 7%
– Distant failure rate = 20%
– Second primary cancer = 34%
Martini et al, J Thor Cardiov Surg 1995; 109: 95 – 110.
• In stage II / III tumors:
–
–
–
–
Intrathoracic failure rate: 31%
5 yr survival in clinical N2 negative nodes: 27%
5 yr survival in clinical N2 positive nodes : 8%
Tumors measuring 1-2 cm have a mediastinal nodal metastasis rate
of 17% as compared to those measuring 2 to 3 cm, when the rate
is 37%
• Patients who fail after surgery, present with extrathoracic
disease 70% of the time, local recurrence in 20% and local
and distant metastasis in 10%.
• 2nd primary lung cancers are known to occur at a rate of 1%
per year in survivors.

60. Role of Radiotherapy
• Plays an important role in the management of
approx 85% of patients with non small cell lung
cancers.
• RT can be applied in the following settings:
– With curative intent
– With Palliative intent
• RT is the most common treatment modality in
majority of patients in India as:
– Majority of the patients present with hilar or mediastinal
disease.
– Disease bulk prevents the use of surgical techniques.
– Associated comorbidities and poor lung function make
patients not suitable for surgery.
– Advanced age and poor socioeconomic status make RT an
attractive treatment option.

61. RT: Advanced Disease
• Aim:
– To achieve local
control due to high
probability of death due
to progression of
systemic disease.
• Indications:
– T3 disease
– N1 or small N2 disease
– No evidence of distant
metastasis
– Weight loss < 12% of
body weight
– < 50% of normal
working time spend in
bed.
• Aim:
– To achieve relief of
symptoms only when
disease is too advanced
for local control
• Indications:
– T4 disease
– Extensive N2 or N3
disease
– Distant metastasis
– Weight loss > 12% of
body weight
– > 50% of normal
working time spend in
bed.

62. Advanced techniques
• Recent innovations
– 3 DCRT
– IMRT
– IGRT
• Respiratory gating:
– Tumors in lung may move by as much as 5-10 mm
during normal quiet breathing.
– The PTV may be effectively doubled if this is taken into
account
– Two techniques of respiratory gating are:
• Breathhold techniques:
– Active : Using valves and spirometers
– Passive: Voluntary breath holding
• Synchronized gating technique : Uses free breathing with
synchronized beam delivery.

63. IMRT

64. Role of Postoperative Radiotherapy
• Indications:
– Advanced disease:
•
•
•
•
Margin positive (< 0.5 cm)
Microscopic or macroscopic residual disease
Hilar or mediastinal node positivity
Mediastinal or chest wall invasion.
• Dose : 30 – 40 Gy in 10-20 # over 2 weeks.
• Why is data regarding PORT inadequate?
– Unlike surgical series none of the studies have taken into
account the extent and site of nodal involvement which
have been found to be important prognostic variables.
– Many studies reported used inadequate doses .

65. Brachytherapy
• As far back as 1922, Yankauer placed capsules of
radium through a rigid bronchoscope into the
region of bronchogenic carcinoma.
• Brochoscopic afterloading flexible applicator based
technique first reported by Mendiondo et al.
• Role:
– As a palliative measure
• Indications:
– Patients with clinically significant endobronchial
component who are not suitable for other forms of
therapy.
– Life expectancy > 3 months.
– Ability to tolerate a bronchoscopy.
– Absence of bleeding diathesis.

66. Intraoperative Brachytherapy
●
Mostly used for
Stage IIIA disease
-
●
close or positive
margins
Improved local
control

67. Cedars Brachytherapy
• 3 radiation catheters
• Minimally invasive
surgery
• Radiation beads are
placed down the
catheters
• Then the beads are
removed
• Very targeted – lung
motion is not an issue
Catheters for
radiation
beads

68. Chemotherapy
&
Targeted therapy

69. Chemotherapy
• Based upon the premise that 70% - 80%
patients will have micrometastasis during
presentation.
• Situations where CCT can be used:
 Neoadjuvant CCT as an induction regimen
 Adjuvant chemotherapy with or without
radiation*
 Palliative chemotherapy in systemic disease.
• No advantage of consolidation
chemotherapy has been established.

70. CCT regimens
• Standard chemotherapy
regimens:
– CAP regimen (q 3 weekly x 6
cycles)
• Cyclophosphamide
• Adriamycin
• Cisplatin
– CVP regimen
• 3 drug regimens have better
response rates but survival
benefit is absent.
• In a study by Schiller et al using
4 different platinum based CCT
regimens* failed to reveal any
benefit of a particular
combination.
22%
Gemcitabine
25%
Paclitaxel
29%
Vinorelbine
30%
Irinotecan
25%
Mitomycin C
27%
Vinbasltine
23%
Ifosfamide
21%
Cisplatin
0%
10%
20%
30%
40%

71. y
Advanced Non-Small-Cell Lung Cancer: 2013 GUIDELINES
First-line Therapy: 2013
Column A
Cisplatin
Carboplatin
Column B
Vinorelbine
Gemcitabine
Paclitaxel
Docetaxel
Pemetrexed
Nab-paclitaxel
Irinotecan
Column C
Bevacizumab
Cetuximab?
Column D
Erlotinib
Crizotinib
Option 1: choose 1 from column A and 1 from column B
Option 2: choose 2 from column B
Option 3: option 1 + column C (for certain patients)
Option 4: choose 1 from column D (for selected patients)
National Comprehensive Cancer Network clinical practice guidelines in oncology: Non-small-cell lung cancer
(v2.2013). www.nccn.org

72. Contenders for Second Line and Beyond
• Non-small cell lung
cancer
–pemetrexed
–gefitinib
• Small cell lung cancer
–topotecan

73. Targeted therapy
• EGFR Inhibitors
– Gefitinib (Iressa)
– Erlotinib (Tarceva)
• EGFR Monoclonal antibodies
– Cetuximab (Erbitux)
• VEGF Monoclonal antibodies
– Bevacizumab (Avastin)
• Many ongoing trials but what has emerged from already
concluded ones is:
 Iressa does not prolong survival & no benefit from adding to
chemo also (IDEAL phase II trials, INTACT & ISEL phase III trials)
 Erbitux may not show any benefit in combination with chemo
 Avastin may show improved response in combination with chemo
but there is increased Grade III hemoptysis in squamous cell
carcinomas (10%).
 Median time to progression increased by a mere 3 months.

74. Gefitinib: Mechanism of Action
EGF/TGFα
R R
Extracellular
Membrane
Intracellular
Proliferation
Growth factors
Chemotherapy/
radiotherapy sensitivity
EGFR-TKI

K K

EGFR-TKI
Signalling
Cell survival
(anti-apoptosis)
DNA
Angiogenesis
Metastasis
R, epidermal growth factor receptor

75. Stereotactic Radiation for Lung Cancer (SBRT)
•
•
•
•
•
•
•
•
• Relatively new treatment
concept
• Established in early 1990s at
Karolinska Institute,
Stockholm, Sweden
• Few fractions/high doses/steep
gradients
• Goal is tumor ablation
indicated
– Medical inoperability
• Improved therapeutic ratio over
fractionated RT courses

76. Stereotactic Body Radiotherapy VS Standard radiotheraypy
Standard radiotherapy – 6 weeks
5 year survival rates 10 – 30%
SBRT – 1 to 5 days
Local control rates 90%
3 year survival rates 56 – 60%
RTOG 0236

77. Results- Tumor Response After RFA
•
•
RFA is the use of high-frequency
electrical current to heat a
specific volume of tissue to
temperatures high enough to
cause destruction of undesired
malignant cells.
• Lifting of the deflated lower lobe
off of the diaphragm and
sometimes with takedown of the
inferior pulmonary ligament in
cases where the tumor is located
in the lower lobe, is beneficial
during ablation to protect the
1
diaphram.
3 months post-RFA

78. CALGB 14053
• Randomized trial of ―sublobar resection‖ vs.
Lobectomy
• Clinical stage IA(T1a) with PFTs adequate
for lobectomy
• Lobectomy
– VATS or Thoracotomy
• Sublobar Resection
– Wedge resection or segmentectomy
– VATS or Thoracotomy

79. Lung Cancer Surgery: future
Wu C-Y, et. al. Ann. Thorac. Surg. 2013 Feb;95(2):405–11.
Gonzalez-Rivas D, et al. Multimedia Manual of Cardiothoracic Surgery. 2012 Mar

80. Conclusions
• Minimally Invasive Lobectomy is the new
standard for early stage lung cancer
surgery
–
–
–
–
Equivalent oncologic results
Decreased morbidity
Faster recovery
Improved completion of adjuvant therapy
• Thoracoscopic (VATS) Lobectomy is well
established
• The roles of sublobar resection and Robotic
surgery require further investigation

81. Wayne McLaren as the Marlboro man (1976)
Dying from Lung Cancer (1992)
Seminar on NSCLC, Department of
Radiotherapy, PGIMER. Moderator :
Dr. R. Kapoor
81

82. Death is a natural event

83. THANK YOU

84. Surgical Resection of the Lung
Standard of Care For Peripheral Nodules
1940’s
1960’s
1990’s
Pneumonectomy
Lobectomy
?Segmentectomy/Wedge (and
adjuvant local/systemic Rx)

85. Randomized Trial of Lobectomy Versus
Limited Resection for
T1 N0 Non-Small Cell Lung Cancer
(125 Lobectomy , 122 Limited Resection)
RJ Ginsberg, LV Rubinstein and Lung
Cancer Study Group
Ann Thorac Surg 1995;60:615-23

86. Lobectomy vs Limited Resection
120
100
80
60
40
20
0
Lobectomy
Limited Resection
10
8
12
0
96
84
72
60
48
36
logrank p=0.088 (one-tailed)
24
0
12
% Survival
Time to death (from any cause) by treatment
Ginsberg and Rubinstein
Ann Thorac Surg

87. Wedge Resection Versus
Lobectomy for Stage I (T1 N0
M0) Non-Small Lung Cancer
Landreneau, et.al.,
J Thorac Cardiovasc Surg
1997;113:691-700

88. Wedge vs Lobectomy for Stage I
NSCLC
120
% Survival
100
80
Wedge
Lobectomy
60
40
p=0.889
20
0
0
10
20
30
40
50
60
Landreneau, et.al.,
J Thorac Cardiovasc Surg 1997;113:691-700

89. Wedge vs Lobectomy for
Stage I NSCLC
Open
WR
VATS
WR
Vs.
Lobe
0
0
Vs.
3.3
0.20*
Postop Stay
(days)
7.7
6.5
Vs.
10.1
0.0002*
Local Recur (%)
17
15
Vs.
5
0.08*
Local/Systemic
Recurrence (%)
24
23
vs.
17
0.43*
Op Mortality (%)
P<
*- all WR (n=95) vs. Lobe (n=124) Statistical Methods: Life Table Analyses
Obtained by Log Rank and Wilcoxson Tests
Landreneau, et.al.,
J Thorac Cardiovasc Surg
1997;113:691-700

90. Comparison Between Sublobar
Resection and 125Iodine Brachytherapy
After Sublobar Resection in High-Risk
Patients with Stage I Non–Small-Cell
Lung Cancer
R. Santos, A. Colonias, D. Parda, M. Trombetta, RH Maley,
R. Macherey, S. Bartley, T. Santucci, RJ Keenan,
RJ Landreneau
Surgery 2003, Oct;134(4): 691-7

91. Results
Sublobar
Resection
(n=102)
Sublobar
Resection
With Brachy
(n=96)
Local Recurrence
19 (18.6%)
1 (1%) p=.0001
Hospital Mortality
0 (0%)
3 (3%) p=ns
Hospital Stay
7 days
8 days p=ns
93, 73, 68, 60%
96, 82, 70, 67%
p=ns
29 (28.4)
22 (23%) p=ns
65%
53% p=ns
Survival %
1, 2, 3 and 4 year
Systemic
Recurrence
Pre-op FEV 1%
predicted
The FEV 1 did not change postoperatively in the sublobar
resection with brachytherapy group in the interval of follow-

92. Lobectomy vs Sublobar
Resection
“Effect of Tumor Size on Prognosis in Patients
with Non-Small Cell Lung Cancer: The Role of
Segmentectomy as a Type of Lesser
Resection”
Okada M, Nishio W, Sakamoto T, Uchino K, Yuki T,
Nakagawa A, Tsubota N.
“J Thorac Cardiovasc Surg. 2005 Jan;129(1):87-93”
An evaluation of surgical resection in 1272 NSCLC
patients

93. Lobectomy vs Sublobar
Resection
5 Year Cancer Specific Survival “Stage I”
TUMOR SIZE
Segmental
Resection
Lobectomy
Wedge
Resection
20 mm or less
96.7
92.4
85.7
20-30 mm
84.6
87.4
39.4
More than 30
mm
62.9
81.3
0
“Okada, M, et al J Thorac Cardiovasc Surg. 2005
Jan;129(1):87-93”