lung cancer - u-szeged.hu
TRANSCRIPT
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Lung cancer
high incidence- smoking
high mortality
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Lung Cancer in the US
• According to 2004 statistics, there were
173,770 new cases and
160,440 deaths yearly
• More deaths from lung cancer than prostate, breast and colorectal cancers combined
• Decreasing incidence and deaths in men; continued increase in women
0
200 000
400 000
600 000
800 000
1 000 000
1 200 000
1 400 000
1 600 000
1 800 000
1 3 5 10
New Cases
Deaths
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Lung Cancer Epidemiology
• Most frequent cause of cancer death
• In 2020 = 5th cause of death
• In 2010 (Canada) = 11200 deaths in men and 9400
deaths in women (27% of all cancer deaths)
• Overall survival at 5 years around 15%
• 90% of cases attributable to smoking and 50% of new
cases in former smokers
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Women & Lung Cancer
• 80,660 new cases were reported in 2004
- Account for 12 % of all new cases
• 68,510 deaths were reported in 2004
- An increase of 150% between 1974 and 1994
• Women are more prone to tobacco effects - 1.5 times
more likely to develop lung cancer than men with same
smoking habits
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Risk factors
• Smoking
• Radiation Exposure
• Environmental/ Occupational Exposure
– Asbestos
– Radon
– Passive smoke
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• Tobacco use is the leading cause of lung cancer
• 87% of lung cancers are related to smoking
• Risk related to:
– age of smoking onset
– amount smoked
– gender
– product smoked
– depth of inhalation
Smoking
Facts
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SCLC (%) NSCLC (%)
3p deletion 90 50-80
3p14.2 80 40
Rb 80-90 15-30
P16 (promoter metilation) 7 16
P53 (mutation) 90 50
C-Myc 10-40 5-10
Ras (H,K,N) 0 20-30
HER2/neu ? 25
Bcl-2 expressio 75-90 25-30
Prokaspase-8 decrease 80 ?
Telomerase 100 80
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Syndroms frequency (%)
Cough 45 - 75 %
Dyspnea 37 - 58 %
Haemoptoe 27 – 57 %
Weight loss 8 – 68 %
Chest pain 27 – 49 %
Hoarseness 2 – 18 %
Recurrent infections 33 – 65 %
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Symptoms secondary to regional metastases
– Esophageal compression -dysphagia
– Laryngeal nerve paralysis - hoarseness
– Symptomatic nerve paralysis - Horner’s syndrome
– Cervical/thoracic nerve invasion - Pancoast syndrome
– Lymphatic obstruction - pleural effusion
– Vascular obstruction - SVC syndrome
– Pericardial/cardiac extension - effusion, tamponade
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Pancoast sy
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Spread
• Lymph Nodes (hylar, mediastinal, supraclav.)
• Lung, Brain, Liver, Adrenal gland, Bones
• 40% of metastasis occurs in the Adrenal Gland
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Diagnostics
Imaging
CT- thorax- locoreg., liver, brain,
bone
PETCT- active tumor, inv.lymph.
nodes, distant metastasis
Clinical
examinationHNO exam.
laboratory, heart status
lung function
Bronchoscopy
biopsy
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Bronchoscopy biopsy, staging
• Biopsia
• Bronchial brush
• Transbronchial biopsy
• Perbronchial aspiration fine needle biopsy
(TBNA, EBUS)
• Bronchial lavage
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Sampling methods
• CT guided biopsy
• Percutan pleural biopsy
• Lymphnode. aspiration biopsy
• Surgical biopsy
– Mediastinoscopy
– Parasternal mediastinotomy
(Stemmer)
– VATS
– Thoracotomia (10%↓)
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Chest CT- biopsy
Chest MR
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Histopathology
• Histological type• TNM
• Grade
• Vascular invasion
• Necrosis
• Proliferation activity
• Mol. Factors: kRAS mutation, EGFR
SCLC
NSCLC
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Two Lung Cancer Cells, Classified
Non Small Cell Lung
Cancer (NSCLC)
• Adenocarcinoma
• Squamous Cell Carcinoma
• Large Cell Carcinoma
Small Cell Lung Cancer (SCLC)
• Oat Cell
• Intermediate
• Combined
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Small cell lung cancer SCLC (15%)
Oatcell
Polygonal
Lymphocyta like
Carcinoid
Bronchial gland carcinomaAdenocystic carcinoma
Mucoepidermoid carcinoma
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SCLC
• Limited StageDefined as tumor involvement of one lung, the mediastinum and ipsilateral and/or contralateral supraclavicular lymph nodes or disease that can be encompassed in a single radiotherapy port.
• Extensive StageDefined as tumor that has spread beyond one lung, mediastinum, and supraclavicular lymph nodes. Common distant sites of metastases are the adrenals, bone, liver, bone marrow, and brain.
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T 1
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T 2
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T 3
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T 3-4
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N 1-2-3
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M 1
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Lung cancer treatment difficulties
• Inoperability
• Locally advanced tumour
Distant metastasis (75-80%)
• Reduced performance status
• associated morbidity ( neuropathy,
thrombosis, pneumonia, pleural fluid)
• Serious co-morbidity
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Prognostic factors• Limited-extended disease, TNM
• performance status
• weight loss
• LDH, albumin
• Histology type (SCLC-NSCLC)
• Hgb,thrombocyte, leucocyte count,
• Biological markers: K-ras mutation, p53 delecion, 3p-chromosoma mutation, micin-antigensk, cell adhesions molekuls
(NCAM), neuroendokrin marker(NSE)
• RT therapy and responce• Cysplatin therapy and responce
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Complex therapy of lung cancer
RT
Surgery
CTX
specific targetted therapy
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Decision on therapy
Tumour specific factors (TNM, hist. G, R) treatment
(surgery, RT) , disease spec. progn. factors
Patient‘s performance and psycho-social status (age,
diseases, organ function, coping, compliance, family)
Consideration of the expectable results and probable
adverse events
Curative- palliative aim - Cost-benefit??
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Chemotherapy
• Cisplatin – Etoposide
• platines – Taxans
• platines – Gemcitabine
• Navelbine
• Topotecan, Irinotecan
Iressa, tarceva – tirosin kinase inhibitors
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Toxicity
Myelotoxicity: leuco-, thrombopenia, anaemia, total aplasia
GI (mucousa): stomatitis, diarrhoe, nausea, vomiting
Skin: anaphylaxia, allergy, alopecia
Cardiotoxicity
Nephrotoxicity
Liver toxicity
Neurotoxicity
Ototoxicity
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SCLC therapy
6 cycle chemotherapy
loco-regional radiotherapy
elective brain irradiation
If CR
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Combined curative therapy of NSCLC
postoperative radiotherapy
adjuvant chemotherapy depending
on histology results
SURGERY
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Combined curative therapy of NSCLC
2-3 cycle induction chemotherapy
concomitant chemo-radiotherapy
restaging
3 cycle chemotherapy depending on
histology results
SURGERY
restaging
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Definitive chemo-radiotherapy
sequential, altered, concomitant
2-3 cycle induction chemotherapy
concomitant chemo-radiotherapy
+ boost
restaging
3 cycle chemotherapy
restaging
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Palliative chemo-radiotherapy
sequential, altered, concomitant
2-3 cycle chemotherapy
concomitant chemo-radiotherapy
vs RT alone
restaging
3 cycle chemotherapy
restaging
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Treatment and Staging
NSCLC
Stage Description Treatment Options
Stage I a/b Tumor of any size is found only in the
lung
Surgery
Stage II a/b Tumor has spread to lymph nodes
associated with the lung
Surgery
Stage III a Tumor has spread to the lymph nodes in
the tracheal area, including chest wall and
diaphragm
Chemotherapy followed by
radiation or surgery
Stage III b Tumor has spread to the lymph nodes on
the opposite lung or in the neck
Combination of
chemotherapy and radiation
Stage IV Tumor has spread beyond the chest Chemotherapy and/or
palliative (maintenance) care
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Techniques of teletherapy
Conformal RT
Stereotaxy
Dinamic target volume shrinkage
IMRT
Image guided therapy
Breathing guided therapy
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Before Irradiation
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After 40 Gy
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IMRT
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Optimalisation of RT
increase of physical selectivity
Dose escalation(75, 84, 92,4Gy)
decrease of irrad
volume
Increase of accuracy
Tumour Normal Tisuues
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Hyperfraktionated, accelerated RT
shemes
• CHART 54 Gy 1,5 Gy /Fr 2x/ day
12 consequent days
• CHARTWELL
• HART
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Procedures of 3D radiotherapy
Collection of information, RT indication for RT within the complex tratment strategy
patient information
Presimulation: patient positioning, (immobilisation), markers, documentation
CT , treatment planning
Resimulation, set up, field verification, irradiation
Target volume shrinkage
supportive care
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Patient positioning,
immobilisation
Simulator
Treatment
planning
Computer
Beam
verification
Simulator/Lin. acc.
CT
MRI
PET
Diagnostics
Procedures of conformal RT
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Identical position -
immobilization
Planning CT, - MRI, PET/CT
Imaging for RT planning
Landmarks, mask,
photo documentation
training
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Before Irradiation After 40 Gy
PTV reduction after 40 Gy
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Jelátadók (ligandok)
RECEPTOROK
JELÁTVITEL
Tirozin kinázok
SEJTMAG
G2 M
G1S
-OH -OH-OH
SUGÁRZÁS
DNS károsodás/
repair
Sejtszaporodás, növekedés
megállítás
apoptozis
angiogenezisgátlás
Bio
lóg
iai
vál
asz
mó
do
sító
és
kem
ote
ráp
ia
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100 mg/m2 cisplatin
100 mg/m2 Etoposid
irradiation
NSCLC simultan chemo-radiotherapy
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6 mg/m2 cisplatin
irradiation
NSCLC simultan chemo-radiotherapy
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50mg/m2 Paclitaxel
irradiation
200 mg/m2 Carboplatin (AUC)
NSCLC simultan chemo-radiotherapy
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Gralla, Griesinger: JTO 2(6) Suppl.2, June 2007
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Palliative
brachytherapy
3x8 Gy
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Side effects of RT
General:nausea, fatigue, loss of appetite, decrease of
blood count
Acute local: dermatitis, oesophagitis- nutritional
difficulties weight loss, pneumonitis
Late sequales: lung fibrosis, heart impairment,
oesophago-bronchal fistule
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Therapeutic index
Tumour response
side effects
type, seriousity,
management, duration
impact on QL
CR, PR, MC, SD, PD
LC, TFS, TTP, OS
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Supportive treatment
Prevention – careful toxicity assessmentmore selective treatment
combination of effective anti-tumour treatment modalities
with different side effect profile
preventive messures: education on life style, roboration,
organ function improvement, skin care, protective agents (amifostine, dextrazoxane,)
psychotherapy (progressive muscle relaxation training, guided imagery,
autogenic training, meditation-leraxation, music, cognitive distraction, group
and individual therapy)
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Supportive treatment
Leukopenia- colony stimulating factors- Filgastrim, Lenogastrim
Thrombonepia – Oprelvekin thrombopoetic growth factor
Anaemia – erythropoetin(CAVE!)
Anti emetic agents
(Anticipatory) –antiemetics+ anxiolytic (lorazeam)
(Delayed) Combination of Dexamethasone and metoclopramide
Serotonine antagonists Ondansetrton, Granisetron, Tropisetron
Symptome (laboratory) oriented: analgetics, antidiarrheal-, antiinflammatory-,
anxiolytic agents, supplementation, dose reduction