Download hgjgkdjf

DR. KOMALDEEP
JUNIOR RESIDENT
PULMONARY MED
TBHP
Causes and Risk factors
of Lung Cancer
diagnosis
Definition of Clinical
Stage
 The extent of disease that can be determined from
 history and physical examination,
 biopsy procedure,
 imaging studies,
 endoscopy, and
 exploration prior to initial treatment.
Importance : Why do we
need Clinical Staging?
 To aid the clinician in the planning of treatment.
 To give some indication of prognosis.
 To assist in evaluation of the results of treatment.
 To facilitate the exchange of information between treatment centres.
 To contribute to the continuing investigation of human cancer.
CLINICAL STAGING
Pre-treatment
PATHOLOGICAL
Post-treatment
• based on findings gathered by the
doctor by non-invasive or
minimally invasive techniques like
• Based on the examination of the
tissue samples obtained from the
primary tumor, nodes or metastasis
physical exam, radiological exam,
endoscopic ultrasound,
bronchoscopy, mediastinoscopy and
thoracoscopy.
• used to plan the initial therapy
• may be modified by additional
information found during
pathological examination
• Helpful in planning additional
treatment and follow-up
CLASSIFICATION
DATA SOURCE
Clinical (pretreatment)
(cTNM)
symptoms, physical examination, imaging,
endoscopy; biopsy; surgical exploration without
resection etc
Pathologic
(pTNM)
surgical resection and pathology
Post therapy
(ycTNM or ypTNM)
after systemic or radiation before
surgery or as primary therapy denoted with a yc
(clinical)
or yp (pathologic)
Retreatment
(rTNM)
at time of retreatment for recurrence
or progression
Autopsy
(aTNM)
as determined at autopsy
Staging and grading
stage
grade
 Cancer stage refers to the size and/or
extent (reach) of the original (primary)
 Tumor grade is the description of a
tumor based on how abnormal the
tumor and whether or not cancer cells
have spread in the body.
tumor cells and the tumor tissue look
under a microscope. It is an indicator
of how quickly a tumor is likely to
grow and spread.
 Dr. Pierre Denoix, a surgical oncologist
(Institut Gustave-Roussy in Paris) analyzed a
series of papers published between 1943 and
1952.
 Published by the International Union Against
Cancer (UICC) in 1968
 The second “international” recommendation
came in 1974 with the support of the American
Joint Committee on Cancer (AJCC).

6th
edition in 1997; 5,319 cases;USA, published
in 2002.
 7the edition; 100,869 patients; 46 sources in 19
countries-, 81,015 were eligible for inclusion.
 7th edition took effect on january 1st , 2010.
1
1977
1978–1983
2
1983
1984–1988
3
1988
1989–1992
4
1992
1993–1997
5
1997
1998–2002
6
2002
2003–2009
7
20o9
2010-
History of staging of
sclc
According to veterans administration lung study group: 2 stages of SCLC.
 Limited stage disease LD SCLC: Confined to the hemithorax of origin, the
mediastinum, or the supraclavicular nodes.
 Extensive stage disease ED-SCLC: Any disease not meeting limited stage criteria
and with Distant metastasis
The international association for the study of lung cancer (IASLC) revised the VALG
classification in accordance with the TNM system.
 LD definition is consistent with stages I to IIIb
 ED is limited to patients with distant metastasis.
TNM Staging system for
Lung Cancer
 T= Tumor : size or contiguous extension of the
primary tumor
 N= Node : the absence, or presence and extent of
cancer in the regional draining lymph nodes.
 M= Metastasis : the absence or presence of distant
spread or metastases involvement in organs and
tissues
“We’re all in the same game; just different levels,
Dealing with the same hell; just different devils.”
Descriptor
Definition
subgroups
T0
No evidence of primary tumour
T1
Tumour <3cm, in the greatest dimension surrounded by lung or
visceral pleura, not proximal than the lobar bronchus
Tumour </= 2cm in greatest dimension
Tumour >2cm but </=3cm in the greatest dimension
T1a
T1b
T2
Tumor >3cm but <7cm or
Tumor with any of the following features:
Involves main bronchus >2cm distal to carina
Invades visceral pleura
Associated with atelectasis or obstructive pneumonitis that extends to
the hilar region but does not involve the entire lung.
T2a : >3 but <5cm
T2b: >5 but <7cm
T2a
T2b
T3
Tumour >7cm or directly invading chest wall, diaphragm, phrenic
nerve, mediastinal pleura or patietal pericardium
Tumour in the main bronchus <2cm distal to carina
Atelectasis/obstructive pneumonitis of the entire lung
Separate tumour nodules in the same lobe
T1 tumor
 Tumor <3cm diameter
 Surrounded by lung or visceral pleura
 Without invasion of more proximal than
lobar bronchus.
 T1a: <2cm
 T1b: >2cm but <3cm
T2 Tumor
 Tumor >3cm but <7cm or
 Tumor with any of the following features:
 Involves main bronchus >2cm distal to carina
 Invades visceral pleura
 Associated with atelectasis or obstructive
pneumonitis that extends to the hilar region
but does not involve the entire lung.
 T2a : >3 but <5cm
 T2b: >5 but <7cm
T3 tumor
 Tumour >7cm with :
 directly invading chest wall, diaphragm, phrenic
nerve, mediastinal pleura or patietal pericardium
 Tumour in the main bronchus <2cm distal to
carina without involvement of carina.
 Atelectasis/obstructive pneumonitis of the entire
lung
 Separate tumour nodules in the same lobe
T4 tumor
Tumour of any size with invasion of :
 Heart, great vessels, trachea, recurrent laryngeal
nerve, esophagus, vertebral body
 Or carina
 Or separate tumour nodules in a different
ipsilateral lobe
Regional lymph nodes (N)
descriptor
definition
N0
No regional lymph node metastasis
N1
Metastasis in ipsilateral peribronchial and/or perihilar lymph
nodes and intrapulmonary nodes, including involvement by
direct extension
N2
Metastasis in ipsilateral mediastinal and/or subcarinal lymph
nodes
N3
Metastasis in contralateral mediastinal, contralateral hilar,
ipsilateral or contralateral scalene or supraclavicular lymph
nodes
N0 & n1
 Metastasis in ipsilateral peribronchial and/or
perihilar lymph nodes and intrapulmonary
nodes, including involvement by direct
extension
 N1 means at least stage IIa
n2
 Metastasis in ipsilateral mediastinal
and/or subcarinal lymph nodes
 N2 means at least stage IIIa
n3
 Metastasis in contralateral mediastinal,
contralateral hilar, ipsilateral or contralateral
scalene or supraclavicular lymph nodes
 N3 means at least stage IIIb
 N3-nodes are clearly unresectable.
Distant metastasis
descriptor
definition
M0
No distant metastasis
M1a
Separate tumour nodules in
a contralateral lobe or
tumour with pleural
nodules or malignant
pleural effusion
M1a contr nod
Distant metastasis in
extrathoracic organs
M1b
M1b
subgroups
M1a pl dissem
m1
 M1a : Separate tumour nodules in a contralateral
lobe
Or
 Tumour with pleural nodules or malignant
pleural effusion.
 M1b: Distant metastasis in extrathoracic organs
Special situations
descriptor
definition
subgroups
Tx, Nx, Mx
T, N or M status cannot be
assessed
Tis
Focus of in situ cancer
Tis
T1
Superficial spreading of
tumour of any size but
confined to the wall of the
trachea or main stem
bronchus
T1ss
GENERAL RULES:
 All cases should be confirmed microscopically.
 Two classifications are described for each site: Clinical classification AND
Pathological classification
 After assigning T, N and M and/or pT, pN and pM categories, these may be grouped
into stages.
 The TNM classification and stage grouping, once established, must remain
unchanged in the medical records.
 If there is doubt concerning the correct T, N or M category to which a particular case
should be allotted, then the lower (i.e., less advanced) category should be chosen.
 In the case of multiple simultaneous tumours in one organ, the tumour with the
highest T category should be classified and the multiplicity or the number of
tumours should be indicated in parentheses.
TNM Groupings
 A tumour with four degrees of T, three degrees of N, and two degrees of M will have
24 TNM categories
 T, N, and M are grouped into so-called anatomic stage/prognostic groups ,
commonly referred to as stage groups.
 Groups are classified by Roman numerals from I to IV with increasing severity of
disease.
 Stage I generally denotes cancers that are smaller or less deeply invasive with
negative nodes
 Stage II and III define cases with increasing tumor or nodal extent
 Stage IV identifies those who present with distant metastases (M1) at diagnosis.
 In addition, the term Stage 0 is used to denote carcinoma in situ with no metastatic
potential. Stage 0 is almost always determined by pathologic examination.
stage grouping :
"shorthand notation"
Stage I Non-Small Cell
Lung Cancer
 Cancer is found only in the lung
 Surgical removal recommended
 Radiation therapy and/or chemotherapy may also
be used
 “If you don’t look at the lymph nodes, everyone has stage 1
dIsease”
Stage II Non-Small Cell
Lung Cancer
 The cancer has spread to lymph nodes in the lung
 Treatment is surgery to remove the tumor and
nearby lymph nodes
 Chemotherapy recommended; radiation therapy
sometimes given after chemotherapy
Stage III Non-Small Cell
Lung Cancer
 The cancer has spread to the lymph nodes located in
the center of the chest, outside the lung
 Stage IIIA cancer has spread to lymph nodes in the
chest, on the same side where the cancer originated
 Stage IIIB cancer has spread to lymph nodes on the
opposite side of the chest, under the collarbone, or the
pleura (lining of the chest cavity)
 Surgery or radiation therapy with chemotherapy
recommended for stage IIIA
 Chemotherapy and sometimes radiation therapy
recommended for stage IIIB
Stage IV Non-Small Cell
Lung Cancer
 The cancer has spread to different lobes of
the lung or to other organs, such as the
brain, bones, and liver
 Stage IV non-small cell lung cancer is
treated with chemotherapy
Limitations of new
classification
 No data at all being included from Africa, South America or the Indian
subcontinent.
 Russia, China, and Indonesia are not represented or only poorly represented.
 The database used for the 7th edition predates the widespread and routine use of
PET which has had an enormous impact on clinical staging algorithms.
 Lympahngitis carcinomatosis is believed to be associated with worse prognosis in
lung cancer patients. However, there is no evidence to support this. The new TNM
classification does not specifically take account of lymphangitis.
OTHER CLASSIFICATION
Ann Arbour  lymphomas
Duke’s classification  colon cancer
Breslow scale and Clark’s level  melanoma
MEDIASTINAL STAGING
 Determining the involvement of the mediastinal lymph nodes.
 Mediastinal lymph nodes status and the presence or absence of direct tumor
mediastinal invasion will determine the eligibility of the patient to treatment
with intention to cure (surgical treatment) or a palliative care intending to
prolong life and better quality of life.
A Brief History
 Naruke et al proposed the 1st lymph node map in the 1960s
 The Next 30 years: Mountain system proposed in 1973(2,155
patients) : The Mountain Era
 Revised in 1997(5,319 patients)
 The IASLC Staging System: Performed by the International
Association for the Study of Lung Cancer
IASLC lymph node map 2009
Supraclavicular nodes 1
Superior Mediastinal Nodes 2-4
 2r 2l right and left upper paratracheal
 3a 3p : prevascular and prevertebral
 4r 4l: right and left lower paratracheal
Aortic Nodes 5-6
 5: subaortic
 6: paraaortic
Inferior Mediastinal Nodes 7-9
 7: subcarinal
 8: paraesophageal
 9: pulmonary ligament
Hilar, Lobar and (sub)segmental Nodes 10-14
 10: hilar
 11: interlobar
 12: lobar
 13: segmental
 14: subsegmental
American Thoracic
Society mapping scheme.
Supraclavicular zone (1)
Superior Mediastinal Nodes (2-4)
 2. Upper Paratracheal
 3A. Pre-vascular
 3P. Pre-vertebral
 4. Lower Paratracheal
Aortic Nodes (5-6)
 5. Subaortic
 6. Para-aortic
Inferior Mediastinal Nodes (7-9)
 7. Subcarinal.
 8. Paraesophageal (below carina).
 9. Pulmonary Ligament
Hilar, Interlobar, Lobar, Segmental and Subsegmental Nodes (10-14)
Non- invasive
invasive
Chest radiography
Mediastinoscopy : GOLD STANDARD
Computed tomography
Video Assisted Thoracic Surgery
PET scan
Anterior Mediastinotomy (Chamberlain procedure;
MRI
Endobronchial Ultrasound with Fine Needle
Aspiration (EBUS-FNA)
Endoscopic Ultrasound with Fine Needle
Aspiration(EUS-FNA)
Transbronchial Fine Needle Aspiration (TBNA-FNA)
CHEST RADIOGRAPHY
 In certain situations, the plain film may be sufficient to detect spread
to the mediastinum.
 For example, the presence of bulky lymphadenopathy in the superior
or contralateral mediastinal areas may be considered adequate
evidence of metastatic disease.
 Can detect pleural effusions that obliterate costophrenic recesses and
lung nodules larger than 7 mm.
 Every patient suspected of having lung neoplasm must have a
posterior-anterior and lateral chest radiograph
 Still, most patients should undergo CT scan of the chest unless they
are so debilitated that no further evaluation or treatment is planned.
COMPUTED TOMOGRAPHY OF
THE CHEST
 The lung lesion itself is more specifically evaluated by CT
scan, characteristics of the primary mass (i.e., smooth
bordered, spiculated, calcified, etc.), the limits of the lesion are
better assessed and the rest of lung parenchyma may be
screened for additional lesions.
 Routine chest CT may also evaluate the presence of distant
metastasis to the liver, adrenals or bones, which are some of
the commonest sites of metastatic disease.
 The bony structures of the thoracic cavity can also be
evaluated by chest CT.
POSITRON EMISSION
TOMOGRAPHY
 This imaging modality is based on the biologic activity of
neoplastic cells.
 PET is better used in conjunction to CT (PET-CT) in which
single machine incorporates CT and PET during the same
scan.
LIMITATIONS :
 Brain metastasis
 Inflammation: TB, fungal etc.
 Slow growing neoplasms: BAC,
carcinoid tumour
 Size smaller than 7mm
MRI
 There are very few circumstances in which
magnetic resonance imaging (MRI) is a useful
tool in staging lung cancer.
 Helps in evaluating limits and possible
invasion in soft tissue, bone and vascular
structures but, with new generations of
multislice CT scans that are capable to perform
three-dimensional angiotomography, MRI has
diminished one of its main indications, which is
to evaluate vascular and neural invasion in
superior sulcus tumor.
 Its main use is to image the brain when
suspecting of metastasis at this organ.
THE SEARCH FOR METASTATIC
DISEASE
 To detect metastatic disease at common metastatic sites, such as the adrenal glands,
liver, brain, and skeletal system, thereby sparing the patient fruitless surgical
intervention.
 Computed tomography of the chest, CT or MRI with contrast of the brain, and 99mTc
nuclear imaging of the skeletal system, whole-body PET scans for extrathoracic
staging.
 False-positive scans- Adrenal adenomas (present in 2% to 9% of the general
population), hepatic cysts, degenerative joint disease, old fractures, and a variety of
nonmetastatic space-occupying brain lesions are present in the general population.
 False-negative scans—that is, metastases are present but not picked up by current
scanning techniques
Invasive Mediastinal
Staging of Lung Cancer
 After distant metastasis has been ruled out, the mediastinal staging is the most
important aspect to focus in these patients.
 The main purpose of the IMS is to differentiate:
a) patients that will benefit from straight surgical resection
b) patients that will benefit from neoadjuvant therapy, followed by surgical resection;
c) patients who will not benefit from surgical resection, and should receive only chemo
and/or radiotherapy.
 In general, patients with lung cancer may be divided in four categories, according to
tomographic characteristics of the primary tumor and the mediastinum, regarding to
size, location and extension of the disease
(proposed by Dr. Frank Detterbeck and adopted by the American College of Chest
Physicians Guidelines for Diagnosis and Management of Lung Cancer)
Group A: extensive mediastinal infiltration by the primary tumor.
Group B: enlarged paratracheal lymph nodes.
Group C: central tumor with normal-sized mediastinal lymph nodes.
Group D: peripheral small tumor with normal-sized mediastinal lymph nodes .
Mediastinoscopy
 The procedure is done through a transverse
cervical incision, with pretracheal dissection
until the mediastinum and introduction of the
mediastinoscope.
 It is possible to perform biopsies of the
following lymph nodes:
 Pretracheal(1), Right and left high and low
paratracheal (3,2R, 2L, 4R, 4L),Subcarinal(7)
 The procedure may also be done with the
videomediastinoscope, allowing a
magnification of the operative field.
 Mediastinoscopy is the gold standard
method to the invasive mediastinal staging,
with which the other methods should be
compared.
Video assisted thoracic
surgery
 Better staging regarding the T descriptor, given we




have the wide approach to the pleural cavity, making
possible a better evaluation of pleural effusion,
pleural metastatic disease, chest wall, diaphragm and
vascular structures invasion.
At the right side, paratracheal lymph nodes are
relatively easily accessed, but left paratracheal lymph
nodes are extremely difficult to be accessed by this
method, due to the great vessel’s anatomy.
VATS not a substitution but is a complementary
procedure to the mediastinoscopy, especially when
there is a left upper lobe tumor with enlarged lymph
node station 5 and 6.
Allows simultaneous resection of the tumour.
Limitation: unilateral approach.
Anterior mediastinotomy
(chamberlain procedure)
 A horizontal incision is done through second left intercostal
space, and the aortic arch and left pulmonary artery are
identified by palpation.
 Regarding to lung cancer staging, anterior mediastinotomy is
used exclusively in selected patients with left upper lobe (LUL)
tumor, aiming to evaluate lymph nodes at the aortopulmonary
window (station 5) and preaortic (station 6).
 When there is cancer spread only to these stations, usually
patients have a better prognosis and, if patients are fit, there are
two possible treatements: 1) neoadjuvant therapy aiming to
posterior pulmonary resection intending to cure; 2)surgical
resection followed by adjuvant chemotherapy.
Endobronchial ultrasound
with fine needle
aspiration
 Accessible lymph nodes by this method are pretracheal (1),
high and down right and left paratracheal (2R, 2L, 4R. 4L),
and subcarinal(7).
 It may be used in substitution to mediastinoscopy, but, if
the results are negative with the EBUS, the
mediastinoscopy should be performed.
 There are many false negatives with EBUS, thus, if a high
index of suspicion exists, a mediastinoscopy should be
performed when EBUS was negative.
 Doppler feature allows for identification of vessels and
landmarks for nodal stations.
Endoscopic ultrasound with
fine needleaspiration
(EUSFNA)
 EUS is performed using an ultrasound transducer
coupled with the flexible esophagoscope.
 This device guides the needle through the esophageal
wall and allows the approach of lymph nodes in
pulmonary ligament(9), paraesophageal(8),
subcarinal(7) and aortopulmonary window(5).
 Additionally, EUS may be able to detect metastatic
disease in sites as left adrenal gland, celiac lymph nodes
and liver and also direct invasion to some mediastinal
structures (T4).
 The ideal procedure is when both (EUS & EBUS)
methods are performed at the same session, with the
patient under general anesthesia or sedation.
Transbronchial
needle aspiration
(TBNA)
 TBNA utilizes a standard flexible bronchoscope
and a needle, known as Wang Needle through the
scope.
 Its main indication is to evaluate enlarged
subcarinal lymph nodes (station 7).
 Negativity of this test should prompt the
mediastinal evaluation by other method, such as
mediastinoscopy.
 Operator dependent.
 TBNA is safe and performed in an outpatient
basis.
Thoracocentesis
 Aspiration and cytological examination of pleural fluid in
patients presenting with suspected malignant pleural effusion
provides a diagnostic yield of approximately 60%;
the addition of needle pleural biopsy may raise the possibility
of detecting cancer to 75%.
 The presence of neoplastic cells in the fluid excludes surgical treatment.
 Will be of help only if there is pleural involvement by the tumor.
 When there is no diagnosis of pleural fluid after thoracocentesis and the effusion is
recurrent, one should perform a videothoracoscopy, which have a sensibility of 95% in
detecting pleural metastasis (by pleural biopsy and fluid analysis), and also has the
advantage of allowing to perform the pleurodesis at the same surgical procedure.
TTNA
 Transthoracic needle aspiration, usually under CT
or fluoroscopic guidance, is an expedient and
relatively safe way to diagnose the primary tumor
mass and establish a diagnosis of lung cancer.
 As a general rule, if a lesion is less than 3 cm in
size and lateral to the mid-clavicular line,
bronchoscopy would not be the diagnostic
procedure of choice. Transthoracic needle
aspiration should be considered under such
circumstances if tissue diagnosis is necessary.
Special Situations
1.Left upper lobe tumors
 Patients with left upper lobe (LUL) tumors deserve a special mention,
because the lymphatic system drains preferentially to lymph nodes in the
aortopulmonary window (station 5) and preaortic location (station 6).
 These nodes are rarely involved by tumors originating from other
pulmonary lobes.
 The approach to station 5 and 6 must be done by anterior
mediastinoscopy or videothoracoscopy, and choosing between these two
methods must be individualized according to each patient
2.Pancoast
tumor
 A Pancoast tumor is a tumor of the superior pulmonary sulcus
characterized by pain due to invasion of the brachial plexus,
Horner's syndrome and destruction of bone due to chest wall invasion.
 Pancoast tumors are staged at least as T3, because there is almost
always chest wall invasion.
 When there is ingrowth into a vertebral body or vital mediastinal
structures, the tumor is staged as T4.
 Ipsilateral supraclavicular nodes (N3) (peritumoral lymph nodes)
are potentially resectable with en bloc resection, while mediastinal
nodes (N2) are not.
 After histological diagnosis, if noninvasive staging points to the
possibility of a pulmonary resection, the mediastinum must
obligatory be invasive staged.
3.Invasive
re-staging after
neoadjuvant treatment
 If previous IMS was positive, it is obligatory to repeat it, more commonly with the
mediastinoscopy;
 If previous IMS was negative and the new CT and PET-CT show neither
enlargement nor augmentation in the SUV when compared to the CT and PET-CT
performed before the neoadjuvant therapy, it is not necessary to repeat the IMS;
 If previous IMS was negative, but the new CT and PETCT reveal mediastinal node
enlargement and/or augmentation in SUV comparing to the CT and PET-CT
performed before the neoadjuvant therapy, the IMS must be performed again,
usually by mediastinoscopy.
 Finally, after neoadjuvant therapy, if N2 or N3 disease is detected in this second
IMS, the patient will not benefit from surgical resection; if there is no N2 or N3
disease, the patient should have a pulmonary resection.
Conclusion : Staging
matters!!!
 Lung cancer staging must have a simple and logical sequence.
 The only possible method to cure this neoplasm is by surgical resection, therefore a
correct staging should be offered to every patient facing this disease.
 The most important point when evaluating a patient suspected of having lung
cancer, refers to the oncological status of mediastinal lymph nodes, and its
evaluation, by means of radiological examinations or invasive procedures, is the
critical part for every patient.
 Every patient should start the investigation with a chest radiograph and chest CT
with intravenous contrast.
 The clinician must be wary of abnormal scans that may falsely suggest metastatic
disease to the mediastinum and distant sites
Conclusion : Staging
matters!!!
 After this initial evaluation, the mediastinal evaluation should be complemented
based on the size of mediastinal lymph nodes, the location and size of the lung
lesion. Recently, PET-CT has been added to the investigation of every patient
who is a potential candidate for pulmonary surgical resection.
 Tissue confirmation by whatever means necessary is the rule rather than the
exception prior to deciding on correct stage and the most appropriate treatment.
 A detailed preoperative workup is essential to choose the most appropriate
therapeutic plan to each patient, with best results regarding to possible cure,
improvement of quality of life, rational use of medical resources and less
morbidity and mortality.