Transcript Lung cancer

General Thoracic Surgery
Cardio-Thoracic Department
Papworth Hospital
University of Cambridge Hospital Trust
Cambridge, UK
Phase III Lecture Programme
Oncology
lung cancer
Marcello Migliore
History
In 1910 Alton Oschner, esteemed surgeon, recalled that as a student at
Washington University he was asked to witness an autopsy of a patient
with lung cancer, having been told lung cancer was so rare that he may
never see another case.
He saw the next case 17 years later.
Within the next 6 months 8 more cases were seen at that hospital
and this began what he called an epidemic.
IA
IIA
IB
IIB
IIIA
Epidemiology
• 1950 Doll and Hill in the British Medical
Journal confirmed suspicions that lung
cancer was associated with cigarette
smoking
Epidemiology
• In 1930 in the USA, lung cancer rates were
less than 5 per 100,000
• In 1998 the death rate per 100,000
population for men reached 77.2 in Belgium
and 75.5 in Scotland.
Epidemiology
What is going on in the developing countries
• In 1994 the rate of lung cancer was similar
to that of the USA in 1930
• In 1999 the rate of lung cancer was 14.1 per
100,000 in developing countries and 71.4 in
developed countries
Lung cancer
Only 25% of patients will undergo surgery
with the hope of curing the disease
Most
75% will not have surgery
Lung cancer
TNM
p TNM
c
TNM
T factor
T1
< 3 cm
T2
> 3 cm, invading visceral pleura, > 2 cm from carina
T3
T4
spread to the chest wall, < 2 cm from carina
spread to the heart, two nodules in the same lobe, +
pleural fluid for malignant cell
T factor
T2 :
> 3 cm, or invading visceral pleura, > 2 cm from carina
T factor
T3 spread to the chest wall, < 2 cm from carina
T4 spread to the heart, two nodules in the same lobe, + pleural fluid for malignant cell
TNM
N factor
N0
Absence of nodal metastasis (MTS)
N1
MTS peribronchial and ilar nodes - same side
N2
N3
MTS mediastinal (same side) and sub carinal nodes
MTS mediastinal and ilar contro lateral, supraclavear and
scalene
Lung cancer
Why it is important to know the status of nodal diseases
Ann Thorac Surg 2002;73:1545-51
cTNM
N
T2
N3
N2
VIDEO - MEDIASTINOSCOPY
Washington University School of Medicine
review of 2137 mediastinoscopies
Morbidity and mortality rates was 0.6% and 0.2% respectively
Sensitivity of 85.2% in the accurate staging of N2 and N3 disease
when used preoperatively in patients with lung cancer.
TNM
M factor
Distant MTS
Or two nodules in different lobes
Lung cancer - STAGE and T N M
STAGE
Tumor
Nodes
Metastasis
IA
IB
T1
T2
N0
N0
M0
M0
IIA
IIB
T1
T2
T3
N1
N1
N0
M0
M0
M0
III A
T3
T1-3
N1
M0
N2
M0
IIIB
T1-4
T4
N3
N0-3
M0
M0
IV
T1-4
N0-3
M1
Mountain 1997,AJCC,UICC
Lung cancer
Pathological and clinical characteristics
1. Squamous
a. Obctructive pneumonitis
b. Lung or lobar collapse
d. 1/3 are in the periphery of the lung
e. 20% are escavated
2. Adenocarcinoma
a. 2/3 are in the periphery
b. < 3 cm
c. Bronchioloalveolar type have diffuse pattern
25-40%
30-50%
3. A great cell (undifferenciated)
1. 60% are in the periphery
2. 2/3 > 4 cm
10-20 %
4. Small cell
1. 80% abnormal lung ilum
2. 2/5 parecnchimal changes
15-25 %
Lung cancer
Clinical presentation
1. Broncho-pulmonary
2. Extrapulmonary but intrathoracic
3. Extrapulmonary metastatic
4. Extra pulmonary non metastatic ( i.e. paraneoplastic)
Lung cancer
Bronchopulmonary Symptoms
Cough (tosse) (most common 75%)
Hemoptysis (33%)
Pain (dolore) (50% poor prognostic sign)
Anorexia and weight loss (poor prognostic sign)
Shortness of breath
Hoarseness (1-8%)
Lung cancer
Clinical Signs
•“clubbing” is the most common
•Pleural effusion
•Pulmonary hypertrophic osteopathy (2-12% of all
patients with lung cancer)
Extra pulmonary non metastatic ( i.e. paraneoplastic)
1) syndromes similar to myasthenia gravis
2) polimyositis
b. Cushing Syndrome - small cell
c. SIADH – small cell
d. Hypercalcemia – squamous cell
e. Gynecomastia – small cell
f. Gonadotropin – indifferenciated great cell
Lung cancer
Diagnosis
Invasive
Not invasive
.......................In every new lung nodule it is
necessary to achieve a final pathologic diagnosis to
exclude the presence of cancer
EVIDENCE BASED MEDICINE
Lung cancer – diagnosis
Chest x ray
Generally radiographic alterations are present 7 months
before symptoms reveal the tumor
It shows nodules > 1 cm
The most common finding is the coin lesion
It failed to demonstrate a reducing in lung cancer mortality
CHEST X RAY
Lung cancer - diagnosis
CT of the chest
a. The best method to evaluate mediastinal adenopathy and renal
glands
b. Invasion of thoracic wall is not always correctly diagnosed
c. Paraesophageal nodes and inferior pulmonary vein are not
visible
d. Nodes < 1 cm have 7% possibility to be malignant
e. Nodes > 1 cm have 55-65% possibility to be malignant
Lung cancer
Diagnosis
CT of the chest
Three studies revealed that using Spiral CT
as a screening method it was possible to
discover 84-93 % of lung cancer in the initial
stage (IA) with a low percentage of false
positive (20%).
Lung cancer
Diagnosis
Magnetic Resonance (MR)
It is better to evaluate the vascular
invasion
MR – Brain metastasis
PET (Positron Emission Tomography)
Higher specificity has the PET con FDG (F18 fluoro
deossiglucosio) (sensibility 95% - specificity 85%) but it
is useful in nodules greater than 6 mm.
It reduces the need to send the patient for an
invasive method such as mediastinoscopy.
CT thorax PET
PET scan N3
Lung cancer
Diagnosis
Sputum cytology
Sensitive in 20- 70%, but it is correlated with the position of
the tumour
Squamous carcinoma is more common to be positive than
small cell or adenocarcinoma.
When cytology is positive a final diagnosis in 85% is
possible
Lung cancer
Diagnosis
Invasive diagnosis
RIGID
FLEXIBLE
BRONCOSCOPY
Haemoptsis
Intraluminal mass
Biopsy
Lung cancer and pleural effusion
Thoracocentesis
Lung cancer - diagnosis
CT GUIDED BIOPSY
Percutaneous o transbronchial
In peripheric lesion is accurate in 85-95%
CT- FNA: 85-95%
sensitive
Complications ?
Lung cancer – invasive diagnosis
VATS
Thoracotomy
Lung cancer
TREATMENT
SURGERY
Lung cancer – preoperative tests
Lung function is mandatory if the patient needs an operation
High surgical risk
1. FEV1 < 40%
2. Predicted postoperative FEV1 < 30%
4. DLCO < 40%
5. PCO2 > 45 mmHg
The goal of surgical treatment in
oncology is twofold
• to achieve long term survival with a good
quality of life
• to avoid recurrence
Surgical treatment of lung cancer
Indications
• cTNM
• Lung Function Tests
• Intra-operative
Lung cancer - Surgical treatment
•
•
•
•
•
•
•
Wedge
Segmentectomy
Lobectomy
Pneumonectomy
Sleeve Resection
Limphadenectomy
Lung transplantation (Bronchioloalveolar ca.)
VATS - ?
Surgical Treatment
Stage I o II
Lobectomy
+ Nodal dissection
VATS Lobectomy
Age and lung resection
Surgical Treatment
Stage IIIA
Neoadjuvant Therapy:
Responder (down
staging)
Surgical treatment
Not responder
chemo therapy
23.9 %!!!
mortality
Bronchiolo – alveolar carcinoma
Stadio IV
T4N0M1
Bilateral Lung TX
Lung cancer
TREATMENT
CHEMO
RADIO
OTHER (stent, laser, photodynamic therapy)
Chemotherapy
Advanced NSCLC
• Over the last 10 years new agents have
provided a better median survival of 7-10
months with 35-40% alive at 1 year.
Chemotherapy
Small Cell Lung Cancer
•
•
•
•
The most frustrating cancer to treat
1970 mean survival was 5 months
Nowadays 18-20 months (limited disease)
Nowdays 6-9 months (extensive disease)
Radiotherapy
• As a curative modality, radiotherapy has been
disappointing.
• The combination of chemo and radiotherapy has
provided better median and long term survival
than radiotherapy alone
• Radiotherapy has proven most successful in
palliating lung cancer symptoms in up to 80% of
instances.
Other
(stent, laser, photodymanic therapy, cryosurgey)
• The main indication is in patients with the occlusion
of the main bronchus or lobar bronchi
• Also indicated in patients in early-stage disease who
are not candidates for surgical procedures. It may also
be used to reduce symptoms in late-stage disease.
NEW APPROACHES
• Mutation in Epidermal Growth Factor Receptor
(EGFR). Aberrant signalling from the EGFR is
known in lung cancer.
• Two oral inhibitors of EGF, geftinib and erlotinib,
inhibit the EGFR and both have demonstrated
antitumor activity.
• Responses to these agent are few. Mainly nonsmokers, women, BAC.
NEW APPROACHES
Immunotherapy. Immunotherapy uses drugs that boost the
patient's immune system to fight cancer.
Gene Therapy. Research is underway to determine if methods
can be developed to attack genetic mutations that are causing cancer.
Angiogenesis Inhibitors. Under investigation are agents that
inhibit the formation of new blood vessels (called angiogenesis). The
spread of new blood vessels is controlled by compounds called growth
factors, such as vascular endothelial cell growth factor (VEGF).
Angiogenesis inhibitors are agents that literally turn off the growth
factors themselves or their receptors.
SUMMARY – in general
•
One hundred year ago lung cancer was rare
•
Only 25 % of patients with lung cancer will have the chance to have the
cancer removed, and therefore the hope of a cure. The majority will
undergo oncologic treatment.
•
Chest x ray modification is present 7 months before the first symptoms.
Chest x ray reveals only nodules > 1 cm.
•
Modern diagnostic tools are “latecomers” and their main role is to
evaluate the possibility of surgical treatment.
•
All the non invasive diagnostic tests do not determine the histology.
(evidence based medicine).
SUMMARY – surgical treatment
• Patients in stage I and II can undergo
surgery after the evaluation of the
respiratory condition
• Patients in stage IIIA are potentially
resectable,
but
they
first
need
neoadjuvant therapy
SUMMARY – surgical treatment
• VATS is probably the best treatment for patients in
stage I
• To avoid or discuss in detail with the patient if R
pneumonectomy is indicated following neoadjuvant
treatment for the high mortality risks
• In case of advanced BAC Lung Transplantation is
an option.
SUMMARY – non surgical treatment
• Chemotherapy is the only option for SCLC
• Radiotherapy is successful in palliating lung
cancer symptoms
• The combination of chemo and radiotherapy has
provided better median and long term survival.
To achieve the best long term survival it is
necessary to reduce the time interval
between
The first clinical symptoms and the final
diagnosis and treatment
2008
Anatomical lung resection is the most appropriate
treatment to achieve better long term survival
adding the hope of curing the cancer in patients at
the initial stage with good lung function
The future
The future in the treatment
of lung cancer
• early diagnosis
•Surgery associated with
other therapies