Edit Csada MD
08.10.2014.
1

Globocan 2012.
 Lung cancer is the most frequent malignant disease
New cases:
Mortality:
1,82 million/year
1,59 million/year
(13%)
Most frequent cause of death amoung malignant diseases>colon+prostate+breast
Europe:~1000 death/day
Lung cancer fatality: breast cancer fatality:
Male/female: 2,4/1
159/1852 = 0,87
0,35
2

 Until 40 years :
 40-49 years:
 50-59 years:
 60-69 years:
 Above 70 years:
1% ↓
10% ↓
~30%
~30%
30% ↓
3

Smoking
Athmospheric pollution
Ionisation
Occupational factors asbestos, radon, etc
Other lung diseases tb, COPD, ILD
Genetic events
4

 400 chemical materials
 60 carcinogens
 Gas and particulate phase
 Nitrosamines, aromatic amines, benzopyrene, CO, CO2, aldehids, nicotin, free radicals
 Pack-year
5

 85-90% of lung cancer patients are smokers
 Damages of 10-15 gens have role in the development of lung cancer
 86% of smokers have damages of these gens
6

 Genetic damages
 Deletion
 Mutations
 Amplifications
Tumor suppressor gen injury (p53, RB1)
Inhibation of proliferation
Repair mechanism
Induction of apoptosis
Protooncogen abnormalities
Autocrine growth factors membran receptors transcription factors
7

AC SCLC SQCLC
Proliferáció/onkogen
EGFR/TK mutáció Amplifikáció(?) 30%
HER2ampl./mut.
KRAS mut.
<5%
5%
CMYC ampl.
Proliferáció/suppr.
Apoptosis
FHIT(vesztés)
20% p53 mut.
50%
Rb(vesztés, metil.) 20%
P16(vesztés, metil.) 50%(?)
80%
30% BCL2 fokozott
Kszpáz8(metil)
DAPK(vesztés) 50%
<5%
20%
20%
50%
20%
50%(?)
80%
30%
50%
LMYC
90%
90%
<10%
80%
80%
80%

SCLC (%) NSCLC (%)
3p deletion
3p14.2
Rb
P16 (promoter metilation)
P53 (mutation)
C-Myc
Ras (H,K,N)
HER2/neu
Bcl-2 expression
Procaspase-8 decrease
Telomerase
90
80
80-90
7
80
10-40
0
?
75-90
80
100
50-80
40
15-30
16
50-60
5-10
20-30
25
25-30
?
80
9

 Primary
 Smoking sessation
 Secundary
 Screening
 X-ray
 LDCT
10

Non small cell lung cancer
Squamous cell carcinoma (30%)
Well, or less differentiated, with or without keratinisation
Adenocancer (45%) acinar papillary bronchioloalveolar with mucus formation
Large cell carcinoma (10%↓) clear cell giant cell
11

12

Small cell lung cancer (15%)
Oat cell
Intermediate cell type
Combined type
Carcinoid tumor
Bronchial gland carcinomas
Adenoid cystic carcinoma
Mucoepidermoid carcinoma
13

14

2020. 04. 12.
Korányi Bulletin 2012
15

2020. 04. 12.
2013.03.

 TNM
 Histology
 Histological differentiation
 Invading vessels
 Necrosis
 Proliferation activity
 Prognostic proteins
17

Symptoms
Cough
Dyspnoe
Haemopthysis
Weight loss
Chest pain
Hoarsness
Frequency (%)
45 - 75 %
37 - 58 %
27
–
57 %
8
–
68 %
27
–
49 %
2
–
18 %
18

 Regional spread
 Superior vena caval sy
 Recurrent laryngeal nerve paralysis
(hoarsness)
 Phrenic nerve paralysis elevated hemidiaphragm
 Horner’s sy
 Pancoast’s sy
 Trachea obstruction
 Oesophagus obstruction
 Pleural effusion
 Lymphatic tumor spread
19

20

2020. 04. 12.
Sárosi Veronika anyaga
21

Pancoast tumor
2020. 04. 12.
Pálföldi Regina anyaga
22

Ectopic parathormon productin, hypercalcaemia
Ectopic production,
ACTH
Cushing-syndrom
Osteoarthropathy, digital clubbing
Eaton Lambert syndrom
Peripherial neuropathy, subacut cerebellar degeneration
Polymyositis, dermatomyositis
Thrombophlebitis migrans, DIC
Nephrosis syndrom
Inappropriate production
(SIADH)
ADH
Squamous cell cancer
+
+
+
-
+
-
-
+
+
Adenocancer
+++
+
-
-
+
++
-
+
+
Small cell cancer
Large cell cancer
+ -
+
+
+++
+
+
+
+
+
-
+
-
+
+
+
+
-
23

2020. 04. 12.
Sárosi Veronika anyaga
24

 Imaging technics
 Endoscopy
 Pathology
 Laboratory tests (?)
25

 Imaging technics
 Chest x-rays
 CT
 MRI
 Isotope scanning
 PET/CT
 Ultrasound
26

 Biopsy
 Brushing
 Transbronchial biopsy
 Transbronchial needle aspiration
(TBNA, EBUS)
 Washing
 BAL
27

 TTB, x-ray or CT supervision
 Percutan pleura biopsy
 Lymphnode aspiration biopsy
 Surgical biopsy
 Mediastinoscopy
 Parasternal mediastinotomy
(Stemmer)
 VATS
 Thoracotomy (10% ↓) 28

 T1a = Tumor ≤2 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus).
 T1b = Tumor >2 cm but ≤3 cm in greatest dimension
29

 T2a = Tumor >3 cm but ≤5 cm in greatest dimension, or tumor with any of the following features: involves main bronchus, ≥2 cm distal to the carina; invades visceral pleura (PL1 or
PL2); or is associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung.
 T2b = Tumor >5 cm but ≤7 cm or less in greatest dimension
30

 T3 = Tumor >7 cm or one that directly invades any of the following: parietal pleural (PL3) chest wall (including superior sulcus tumors), diaphragm, phrenic nerve, mediastinal pleura, or parietal pericardium or tumor in the main bronchus (<2 cm distal to the carina b but without involvement of the carina) or associated atelectasis or obstructive pneumonitis of the entire lung or separate tumor nodule(s) in the same lobe
31

 T4 = Tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina, or separate tumor nodule(s) in a different ipsilateral lobe.
32

 N0 = No regional lymph node metastasis.
 N1 = Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension.
 N2 = Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s).
 N3 = Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s).
33

 M0 = No distant metastasis.
 M1a = Separate tumor nodule(s) in a contralateral lobe tumor with pleural nodules or malignant pleural (or pericardial) effusion
 M1b = Distant metastasis (in extrathoracic organs).
34

 Liver:
 Bones:
CT, ultrasound, PET/CT scintigraphy, CT, PET/CT
 Adrenals: CT, ultrasound, PET/CT
 Brain: MRI, CT
36

 Poor performance status
 Karnofsky, WHO ECOG
 Weight loss, more than 10%
 Elevated LDH
 Elevated tumormarker (CEA, NSE, SCC)
 Old age
37

2
3
4
5
Grade
0
1
ECOG
Fully active, able to carry on all pre-disease performance without restriction
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
Dead
38

Karnofsky scale Description
100 Normal; no complaints; no evidence of disease
90
80
70
60
Able to carry out normal activity; minor signs or symptoms of disease
Normal activity with effort; some signs or symptoms of disease
Cares for self; unable to carry on normal activity or do active work
Requires occasional assistance, but is able to care for most of his/her needs
50 Requires considerable assistance and frequent medical care
40
30
20
10
0
Disabled; requires special care and assistance
Severely disabled; hospitalization is indicated although death not imminent
Very sick; hospitalization necessary, active supportive treatment necessary
Moribund; fatal processes progressing rapidly
Dead
39

 Surgery
 Radiotherapy
 Radiochemotherapy
 Chemotherapy
 Molecular target therapy
 Supportive treatment
40

 The type of surgical procedure depends on staging, the patient ’s performance status, cardiopulmonal function and comorbidities.
 The aim is radical resection
 Sublobar resection may have a role in very early diseases.
 Thoracotomy
 Video assisted thoracoscopy (VATS)
41

 Absolute contraindications:
 haematogen metastases in the lungs
 pleuritis carcinomatosa
 III.b stage disease
 multiplex distanti metastases
 Relative contraindications
42

 NSCLC IIIA stage
 Lobectomy, pulmonectomy, sleeve lobectomy, extensive resection – radical
 Segmentectomy, wedge resection – mostly non radical
 Early stage SCLC, as part of combined therapy
 Carina resection?
 Before surgery: lung function, Ecg, functional evaluation
43

 NSCLC: III.A, III.B stage
 SCLC: combined with chemotherapy
 Inoperable patient with resecable disease
 Resected N2 disease, in combined treatment
 Metastasis palliation
 Pancoast’s tu
 Brain metastasis (stereotactic, whole brain)
 PCI
 Brachytherapy
Radiochemotherapy!
44

 Sequential
ChT

RT
 Concomitant
(ChT

RT

ChT)
ChT/RT
 Timing
- Induction: ChT

ChT/RT
- Consolidation: ChT/RT

ChT
45

 Neoadjuvant treatment
 Before surgery IIIa stage
 Adjuvant treatment
 After surgery II-IIIa stage
 First-, second-, thirdline …..
 IIIb, IV stage
46

 Chemotherapy
 Cis-, carboplatin-gemcitabin
 Cis-, carboplatin-paclitaxel
 Cisplatin-docetaxel
 Cisplatin-vinorelbin
 Cisplatin-pemeterexed (non squamous c)
 Doublet+bevacizumab(adenoc)
 Adenoc.: EGFR mutácio pozitivitás
 Erlotinib, gefitinib, afatinib
47

 Chemotherapy
 Docetaxel monoterapy
 Pemetrexed monoterapy
 Adenoc.: EGFR mutation positivity/KRAS negativity
 gefinitib, erlotinib
48

Klasszikus kezelés
Elsővonalbeli kezelés
Platinaalapú kettős kombináció
(4 –6 ciklus)
Kezelési szünet
Másod- és többedvonalbeli kezelés
Diagn ózis CR/PR/SD PD PD
Új megközelítés
Bevacizumab
Pemetrexed ellotinib
Fenntartó kezelés
PDig eltelt idő megnyúlik
Diagn ózis CR/PR/SD PD PD

Surgery in SCLC
 I/A-I/B: resection
 Postoperative chemotherapy
 Adjuvant irradiation in positive node status
 Induction chemohterapy

Chemoterapy in SCLC
 Absoute indication
 Cisplatin/carboplatin-Vepesid
 ECO (epirubicin-cyclophoscphamid-vincristin)
 Topotecan (Hycamtin) (2. line)
 Progression:
 Within 3 months (resistant disease): new combination
 Over 3 months (senzitive disease): reinduction therapy with the original drugs

Radiotherapy in SCLC
 LD: radio-chemotherapy
 PCI: preventíve cerebral irradiation
 In LD and ED
 Remission after treatment
 Dose: 25-30 Gy
 Possible impairment of neurocognitive functions

 EGFR tirosin kinase inhibitors
 Erlotinib (Tarceva)
 Gefinitib (Iressa)
 afatinib
 Angiogenesis inhibitors (VEGF)
 Bevacizumab (Avastin)
 Alk-EML4 fusion gen inhibitor
 Crizotinib (Xalkori)
53

 Pain control
 WHO suggestion
 Adverse events control
 Thrombosis prophylaxis
 Malignant pleural fluid treatment
 Bone metastases treatment
 Endobronchial palliation
 Nutrition
54

Strong opioid ± non opioid ± adjuvant
III.
Weak opioid ± non opioid ± adjuvant
II.
Non opioid ± adjuvant
24 h
I.
24 h 24 h
55

 Pain control
 Adverse events control
 febrile neutopenia
 Anaemia (erythropoetin)
 Nausea, vomiting
 Thrombosis prophylaxis
 Malignant pleural fluid treatment
 pleurodesis
 Bone metastases treatment
 bisphosphonat
 Endobronchial palliation
 Nutrition
56

 I. stage: 55-80%
 II. stage: 30-50%
 III.a stage: 10-30%
 III.b stage: 4%
 IV. stage: 1%
 Five year survival: 15-17%
57

58
Thank you for your attention!