Transcript
Lung cancer
high incidence- smoking
high mortality
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
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1 3 5 10
New Cases
Deaths
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
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
Risk factors
• Smoking
• Radiation Exposure
• Environmental/ Occupational Exposure
– Asbestos
– Radon
– Passive smoke
• 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
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
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 %
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
Spread
• Lymph Nodes (hylar, mediastinal, supraclav.)
• Lung, Brain, Liver, Adrenal gland, Bones
• 40% of metastasis occurs in the Adrenal Gland
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%↓)
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
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
Small cell lung cancer SCLC (15%)
Oatcell
Polygonal
Lymphocyta like
Carcinoid
Bronchial gland carcinomaAdenocystic carcinoma
Mucoepidermoid carcinoma
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
T 2
T 3
T 3-4
N 1-2-3
M 1
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
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
Complex therapy of lung cancer
RT
Surgery
CTX
specific targetted therapy
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??
Chemotherapy
• Cisplatin – Etoposide
• platines – Taxans
• platines – Gemcitabine
• Navelbine
• Topotecan, Irinotecan
Iressa, tarceva – tirosin kinase inhibitors
Toxicity
Myelotoxicity: leuco-, thrombopenia, anaemia, total aplasia
GI (mucousa): stomatitis, diarrhoe, nausea, vomiting
Skin: anaphylaxia, allergy, alopecia
Cardiotoxicity
Nephrotoxicity
Liver toxicity
Neurotoxicity
Ototoxicity
SCLC therapy
6 cycle chemotherapy
loco-regional radiotherapy
elective brain irradiation
If CR
Combined curative therapy of NSCLC
postoperative radiotherapy
adjuvant chemotherapy depending
on histology results
SURGERY
Combined curative therapy of NSCLC
2-3 cycle induction chemotherapy
concomitant chemo-radiotherapy
restaging
3 cycle chemotherapy depending on
histology results
SURGERY
restaging
Definitive chemo-radiotherapy
sequential, altered, concomitant
2-3 cycle induction chemotherapy
concomitant chemo-radiotherapy
+ boost
restaging
3 cycle chemotherapy
restaging
Palliative chemo-radiotherapy
sequential, altered, concomitant
2-3 cycle chemotherapy
concomitant chemo-radiotherapy
vs RT alone
restaging
3 cycle chemotherapy
restaging
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
Techniques of teletherapy
Conformal RT
Stereotaxy
Dinamic target volume shrinkage
IMRT
Image guided therapy
Breathing guided therapy
Before Irradiation
After 40 Gy
IMRT
Optimalisation of RT
increase of physical selectivity
Dose escalation(75, 84, 92,4Gy)
decrease of irrad
volume
Increase of accuracy
Tumour Normal Tisuues
Hyperfraktionated, accelerated RT
shemes
• CHART 54 Gy 1,5 Gy /Fr 2x/ day
12 consequent days
• CHARTWELL
• HART
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
Patient positioning,
immobilisation
Simulator
Treatment
planning
Computer
Beam
verification
Simulator/Lin. acc.
CT
MRI
PET
Diagnostics
Procedures of conformal RT
Identical position -
immobilization
Planning CT, - MRI, PET/CT
Imaging for RT planning
Landmarks, mask,
photo documentation
training
Before Irradiation After 40 Gy
PTV reduction after 40 Gy
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
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
100 mg/m2 cisplatin
100 mg/m2 Etoposid
irradiation
NSCLC simultan chemo-radiotherapy
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
6 mg/m2 cisplatin
irradiation
NSCLC simultan chemo-radiotherapy
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
50mg/m2 Paclitaxel
irradiation
200 mg/m2 Carboplatin (AUC)
NSCLC simultan chemo-radiotherapy
Gralla, Griesinger: JTO 2(6) Suppl.2, June 2007
Palliative
brachytherapy
3x8 Gy
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
Therapeutic index
Tumour response
side effects
type, seriousity,
management, duration
impact on QL
CR, PR, MC, SD, PD
LC, TFS, TTP, OS
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)
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
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