This document provides an overview of the management of non-small cell lung cancer (NSCLC). It discusses the anatomy of the lung and lymph node mapping. The clinical features, diagnostic workup including imaging and staging are covered. The various treatment approaches for early, locally advanced and metastatic NSCLC including surgery, radiation therapy, chemotherapy and targeted therapy are summarized. Techniques for radiation therapy planning and delivery such as 3D conformal radiation therapy, stereotactic body radiation therapy, proton beam therapy and brachytherapy are also outlined.

1. MANAGEMENT OF
NON SMALL CELL
LUNG CANCER
Dr. Ankita Pandey
JR 2
1

2. Anatomy of lung
2

3. Anatomy of lung
 Bronchopulmonary segment is the functional
unit of the lung and is defined by the
segmental bronchi
 Each bronchopulmonary segment consists of
1. Bronchus
2. Artery
3. Vein
4. lymphatics
3

4.  Lymphatics from each bronchopulmonary segment
drains into mediastinum
 Rich lymphatic network within thorax leads to
complex variability in drainage pattern
The international association for the study of lung
cancer developed lymph node map that provide
precise anatomic definitions for all lymph node
stations.
4

5. IASLC lymph node map
5

6. Clinical features
In NSCLC, half of the patients presents
with localised or locally advanced disease
while half presents with advanced stage
In SCLC, 20-30% cases presents with
localised or locally advanced disease while
70-80% presents with advanced stage
6

7. 1. Cough
2. Dyspnea
3. Hemoptysis
4. Chest pain
5. Hoarsness of voice
6. SVC syndrome- SCLC
7. Pancoast syndrome- NSCLC
8. Bone pain
9. Headache, visual disturbances
7

8. Sites of distant mets
 Lymph node mets – most common
 Liver
 Adrenals
 Bones
 Brain
 Kidney
 Pancreas
 Contralateral lung
 Pleura
8

9. Paraneoplastic syndromes
 It is a disease or symptom that is the
consequence of cancer cells in the body but is
not attributable to the local presence of tumor.
 Treating the tumor usually resolves the
syndrome
Caused by-
1. Humoral factors secreted by
tumor
2. Immune response against tumor
9

10. 1. Cushing syndrome
2. SIADH
3. Hypercalcemia
4. Lambert eaton myasthenic syndrome
5. Hypertrophic osteoarthropathy
10

11. Diagnostic staging and workup
 History and physical examination
 PFT
 Assess the overall health status
11

12. Investigations
 CT Scan thorax and upper abdomen
 PET CT
 Percutaneous fine needle aspiration
 Bronchoscopy
 Endoscopic ultrasound
 Thoracocentesis
 Mediastinoscopy
It should be considered in
patients with suspected lung
cancer even if chest x ray is
normal
Liver mets and adrenal
mets
12

13. Staging
13

14. 14

15. Variants of NSCLC
 Adenocarcinoma (50%)
 Squamous cell carcinoma (35%)
 Large cell carcinoma (15%)
15
Histology is important
determinant in selection of
systemic therapy for
advanced NSCLC

16. Treatment algorithm
16

17. Management of stage I and II
NSCLC
 PRE OPERATIVE ASSESSMENT
1. Predicted postop FEV1 >60%
2. DLCO >60%
17

18. Management of stage I and II
NSCLC
 Standard care for stage I and II lung cancer is
surgical resection
Lobectomy with mediastinal LN dissection
 Standard of care for medically inoperable
early stage NSCLC is – SBRT
18

19. Types of surgeries
19

20.  What is the role of limited resection?
Limited resection is either wedge resection or
segmentectomy
 Trial by lung cancer study group- included T1-
2N0 NSCLC.
 Study confirmed lobectomy as standard of care
for early stage lung cancer
20
Limited resection Lobectomy
Risk of recurrence= 17% Risk of recurrence= 6%

21. What are the survival results after
surgery ?
 According to the recent IASLC lung cancer
staging project, following surgical resection for
lung cancer, the 5-year survival is -
 73% for stage IA
 58% for stage IB
 46% for stage IIA
 36% for stage IIB
21

22.  What is the role of mediastinal lymph node
dissection?
American college of surgeons oncology group
trial randomised N0 or N1 patients to
mediastinal LN sampling or dissection and
found no significant difference in DFS, LRR
and distant recurrence
Controversia
l
22

23.  Advantage of mediastinal LN dissection-
Complete mediastinal lymphadenectomy
provides surgical staging by removing all
lymph nodes.
This can help to identify patients who may
require postoperative adjuvant radiation
therapy
23

24. Indications of post op RT
 Positive surgical margin
 Pathologically N+ disease
24

25. Inoperable early stage NSCLC
Inoperable incurable
It simply means patient is medically not fit for
surgery due to old age/ cardiopulmonary
dysfunction/ chronic illness
25

26. Inoperable early stage NSCLC
 Radiotherapy with or without chemotherapy
remains the primary alternative to surgery for
inoperable NSCLC patients.
 higher radiation doses, greater than 70Gy,
enhanced local tumor control or survival.
 high doses increase the probability of normal
tissue toxicity
 Hence , it has poorer outcome compared to
surgery
26

27. Radiotherapy techniques
 2D conventional planning
 3D CRT/IMRT
 SBRT
 Brachytherapy
 Proton beam therapy
Respiratory
motion
management
27

28. Management of Stage III
NSCLC
 Stage IIIA= considered operable
 Stage IIIb= inoperable
28

29.  Primary surgery followed by
chemotherapy has been the
standard.
 Induction radiation therapy
or induction chemotherapy
followed by surgical
resection have been used to
downstage disease and are
considered options in
selected cases of non-bulky,
single-station N2 disease.
 Concurrent
chemotherapy and
radiation therapy
have been
considered the
standard treatment
Operable stage III Inoperable stage III
29

30. Role of Preoperative CCRT
 Results from phase III studies in patients with
stage IIIA non-small-cell lung cancer with
ipsilateral mediastinal nodal metastases (N2)
have shown the feasibility of resection after
concurrent chemotherapy and radiotherapy with
promising rates of survival
30

31. Role of preop chemotherapy
 There are multiple trials in which patients
undergoing surgical resection were
randomized to induction chemotherapy vs
surgery alone
31

32. Role of adjuvant chemotherapy in
stage IIIa NSCLC
 administration of adjuvant cisplatin-based
chemotherapy has become the standard of care
for patients with resected stage II and IIIA
disease
Lung Adjuvant Cisplatin Evaluation Meta-
analysis
32

33. Postoperative Radiation
Therapy
 Postoperative radiation therapy improves local
control and disease-free survival duration for
patients with pathologic N2 disease (Lung
Cancer Study Group 1986).
 a secondary analysis of the Adjuvant
Navelbine International Trialist Association
(ANITA) randomized study showed that PORT
improved overall survival in patients with N2
disease
33

34. Postoperative Radiation
Therapy34

35. Treatment of stage IIIB NSCLC
and inoperable stage IIIA NSCLC35
 Definitive radiotherapy
 Dose- 60-75Gy to gross disease
50Gy to microscopic disease
 RTOG 7301 trial- 60Gy as standard
 RTOG 8311 trial- 69.6Gy/1.2Gy per#/ twice daily
as standard regimen
 Hyperfractionation shows better result

36. Chemoradiotherapy
 A meta-analysis of six trials consisting of 1205
patients revealed that there was an absolute
benefit of 5.9% at 3 years in patients receiving
concomitant chemoradiation.
 improved locoregional progression, but did not
have an effect on distant progression.
 Severe acute esophagitis significantly increased
from 4% to 18%
36

37. Concurrent chemoRT regimens
 Cisplatin and etoposide
 Cisplatin and vinblastine
 Cisplatin and pemetrexed
 Carboplatin and pemetrexed
 Carboplatin and paclitaxel
37

38. Sequential vs concurrent
chemoRT38

39. Stage IV NSCLC
 Stage IV disease is incurable and treatment is
palliative.
 Treatment consists of palliative chemotherapy,
palliative radiation therapy, medications,
supportive care, and hospice care
39

40. Palliative RT
Mets Total dose Dose per fraction
Brain mets 30Gy 3Gy
Bone mets 20-30Gy 3-4Gy
Obstructive ds 30-45Gy 3Gy
40

41. Palliative chemotherapy
 Cisplatin
 Carboplatin
 Paclitaxel
 Docetaxel
 Venorelbine
 Gemcitabine
 Etoposide
 Bevacizumab
41

42. Targeted therapy
 Indicated in patients who have failed
platinum/taxane based chemotherapies
 Anti- EGFR agents-
1. Cetuximab
2. Panitumumab
3. Geftinib
4. Erlotinib
 VEGF monoclonal antibodies- bevacizumab
 ALK + patients - crizotinib
42

43. Radiotherapy techniques43

44. RT planning
 Lung tumor radiotherapy planning is complex
due to motion management.
 Respiratory motion management techniques
include-
1. Breath hold technique
2. Abdominal compression technique
3. Respiratory gating
4. Tumor tracking
5. ABC
44

45. Abdominal compression technique
 For forced shallow breathing
 A plate compresses the abdominal wall few
centimeters below the xiphoid
 This plate is fixed to the arch
 Arch is attached to the body frame
45

46. ABC ( active breathing
coordinator)
 Allows to pause a patient's breathing at a
precisely indicated tidal volume and coordinate
dose delivery
 Consist of Spirometer and balloon valve
 Breath-hold: 15-20 sec
 Self Gated technique
 Patients press switch when breath hold is
achieved
46

47. Respiratory gating
47

48. Real time tumor tracking
 Monitor tumor motion and synchronize the
radiation beam with tumor motion
 Real-time tracking using (i) dynamic MLC (ii)
Robotic couch
 Interrupt and restart the treatment when target
motion differs from the simulated pattern
48

49. CT simulation
Motion artifacts in free breathing
CT scans
Scan speed slower
than tumor motion
speed
Image of
tumor is
blurred
Scan speed faster
than tumor motion
speed
Tumor image
represents
arbitary phase
of respiration
Scan speed
similar to tumor
motion speed
Tumor
image is
distorted
49

50. 4D CT
 4D CT provide multiple datasets for assessing
target motion during breathing
 Longer than conventional CT
 More dose
 Provides upto 10 different phases or sets of
CT images
50

51. 51

52. 4D CT
 PTV margin is reduced
 Less dose to normal tissue
 Dose escalation is possible
 Better tumor control
52

53. 2D radiotherapy planning
53

54. 54

55. 55

56. 3D planning
 GTV
 Macroscopic ds identified on imaging
 Lung window- for delineation of primary tumor
 Mediastinal window- for mediastinal
extensions
 LN >1cm is considered diseased
56

57. The Role of the PET Scan on
Target Delineation
 It distinguishes tumor from collapsed lung or
mediastinal structures.
 It detects mediastinal nodal involvement more
accurately, allowing an estimate of the ITV,
because the PET images are usually acquired
over an extended period (normally approximately
30 minutes).
 It decreases interobserver and intraobserver
variations in target delineation.
57

58. CTV
 Volumetric expansion of GTV to encompass
microscopic disease
6mm for squamous cell cancer
8mm for adenocarcinoma
9mm for others
 CTV of primary should not extend into chest wall or
mediastinum
 3mm margin around LN <2cm. Larger margins
required for LN >2cm
 In PORT, CTV includes the bronchial stump and high
risk draining LN stations
58

59. Internal Target Volume (ITV)
 tumour volume obtained using a 4DCT scan.
This is defined as tumour contoured using
either the
(i)maximum intensity projection scan,
(ii) maximum inspiratory and expiratory scans or
(iii) as contoured on all 10 phases of a 4DCT
scan.
59

60. PTV
 Volumetric expansion of CTV
 Decreased by immbilization, motion
management and IGRT techniques
60

61. SBRT
 SBRT also known as SABR uses short
courses of ablative , highly conformal and
dose intensive RT delivered to limited size
targets.
 Current standard of care for early stage non
operative NSCLC is SBRT
61

62. Patient selection criteria for
SBRT
1. Medically inoperable
2. Good PS
3. Able to lie on couch
4. Stage T1-3, N0
5. Not adjacent to great vessels/ esophagus/
heart
62

63. Types of lung lesion according to
location
a. Peripheral
lesionLesion located >2cm
from primary bronchi
or trachea
Lesion located within
2cm of primary bronchi
or trachea
Lesion abutting
central airways
63

64. Difference between fractionated
EBRT and SBRT64

65. SBRT dose
65

66. SBRT dose
 The dosing schemes used should achieve a
BED of >100 Gy, and dose fractionation
should be based on whether the tumor is
peripherally or centrally located.
 minimize normal tissue toxicities by using
multiple beams (>6, but typically 9–12)
66

67.  Two important principles of SBRT must be
obeyed:
(1) An ablative dose (BED>100 Gy) prescribed
to PTV is required to achieve >90% local
control and
(2) image-guided tumor volume delineation
and onboard image-guided radiation therapy
(IGRT) are required to account for daily
target/normal tissue motion so that the target
is not missed and to avoid normal tissue injury
67

68. 68

69. Proton beam therapy
 proton therapy delivers its therapeutic dose to
a certain depth (as defined by the Bragg peak)
without any exit dose
 Advantage- tumor dose escalation is possible
without causing normal tissue toxicity
69

70. 70

71. Brachytherapy
 Interstitial brachytherapy
 Endoluminal brachytherapy
71

72. Indications of endobronchial
brachytherapy
 Palliation of endobronchial disease recurring
after external beam radiotherapy
 Palliation of endobronchial disease from
metastatic disease
 Boost treatment after initial course of definitive
EBRT for primary cancer with endobronchial
component
72

73. Technique of endobronchial
brachytherapy
 100-cm-long 6-French catheter placed under
bronchoscopic guidance
 Catheter placed distal to area of obstruction with
visualization using dummy wires threaded through
catheter
 Localization films taken for treatment planning
(determination of length to be treated and initial
dwell positions)
 Dose prescription point 1 cm from source center
and 1–2 cm linear margin on the target
 Prescribed dose of 5 Gy in 3–4 fractions or 7 Gy
in 3 fractions with 1-week intervals between
treatments
73

74. Side effects of radiation
therapy
74

75. Acute Sequelae of therapy
 Esophagitis
 Skin reactions
 cough
75

76. Late sequelae
 Pneumonitis
 Pulmonary fibrosis
 Esophageal strictures
 Cardiomyopathy
 Spinal cord myelopathy
 Brachial plexopathy
76

77. Take home message
 Non–small cell lung cancers (NSCLC) account for over 85% of all cases;
the rates of small cell lung cancers (SCLC) fall with the reduction in
smoking rates.
 The most common presenting symptoms include dyspnea, cough, and
weight loss.
 Lobectomy is the standard treatment for early-stage NSCLC, although
stereotactic body radiation therapy is a good option for medically inoperable
patients.
 The optimal management of locally advanced NSCLC is controversial.
Treatment includes either definitive chemoradiation therapy or surgical
resection and lymph node dissection, with either induction or adjuvant
chemotherapy.
 Postoperative radiotherapy is indicated for positive-margin disease and
perhaps for patients with pathologic N2 disease.
 After surgical resection for stages IIA–IIIA NSCLC, adjuvant therapy with
platinum- based chemotherapy is now the standard of care.
77

78. Thank you
78