Lung cancer - u-szeged.hu

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

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

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

10

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

13

Bronchoscopy biopsy, staging

• Biopsia

• Bronchial brush

• Transbronchial biopsy

• Perbronchial aspiration fine needle biopsy

(TBNA, EBUS)

• Bronchial lavage

14

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

16

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.

20

21

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


+ boost

restaging


restaging

Palliative chemo-radiotherapy

sequential, altered, concomitant

2-3 cycle chemotherapy


vs RT alone

restaging


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


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)


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

Lung cancer - u-szeged.hu

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