Rome, May 15-16, 2009

Enrico Cortesi, Martina Puglisi

Sapienza, Universit di Roma
0%
0%
100%
0%
0%
Which rate of patients with Malignant Pleural
Effusion (MPE) experiences reaccumulation of
fluid within 30 days after thoracentesis?
28 / 30
Cross-tab label

1. 30-40%
2. 80-90%
3. 95-100%
4. 10-20%
5. 0%

In which cases should pleurodesis be
considered as a valid therapeutic option?
1. Adeguate PS and patients life
expectancy (eg longer than 3
months)
2. Patients dyspnea improved after
therapeutic thoracentesis
3. The underlying tumor and
resulting Malignant Pleural
Effusion are not responsive to
chemotherapy or radiotherapy
4. All the answers above
5. None of the answers above

29 / 30
Cross-tab label
1
24%
2
17%
3
3%
4
52%
5
3%

The presence of Malignant Pleural Effusion is
required to stage a NSCLC as :
1. Stage III B
2. Stage III A
3. Stage IV
4. It is not arleady
established
5. Malignant Pleural Effusion
is not considered for
staging

29 / 30
Cross-tab label
0% 0%
97%
3%
0%
1 2 3 4 5

Malignant Pleural Effusion (M.P.E.)
An M.P.E. is defined by the presence
of cancer cells in the pleural space
Malignant Pleural Effusion (M.P.E.)
An M.P.E. is defined by the presence
of cancer cells in the pleural space
Underlying Primary Cancer
1.Lung tumors (including malignant pleural
mesothelioma) NSCLC: 14% at the time of
diagnosis, 50% with advanced disease
2. Breast cancer
3. Ovarian cancer, gastric cancer
4. Hodgkins and non-Hodgkins lymphoma
Malignant Pleural Effusion (M.P.E.)
An M.P.E. is defined by the presence
of cancer cells in the pleural space
Cancer cells reach the visceral pleura (through the pulmonary
vasculature)or the parietal pleura (through hematogenous spread)
Cancer cells in the pleural space
(tumor deposit along parietal pleura)
A. Obstruct lymphatic stromata (which drain intrapleural fluid)
B. Release chemockines ( increasing vascular permeability)
Malignant Pleural Effusion (M.P.E.)

Paramalignant Effusion
1. Mediastinal lymph node tumor infiltration
2. Bronchial obstruction/Atelectasis
3. Pulmonary embolism
4. Superior vena cava syndrome
5. Decreased oncotic pressure (cachexia)
6. Radiotherapy/Chemotherapy

Malignant Plural Effusion
And
Diagnosis
M.P.E. and Diagnosis
Cytologic or tissue biopsy confirmation is
required to establish a diagnosis of MPE
M.P.E. and Diagnosis
Cytologic or tissue biopsy confirmation is
required to establish a diagnosis of MPE
Diagnostic thoracentesis:
Diagnostic yield of PF cytology ranging from 62 to 90%
Positive results on cytology might not differentiate
between adk subtypes or between pleural adk and
mesothelioma
Additional PF studies could complement standard
cytology: Electrochetoluminescence for tumor markers,
genetic analysis

M.P.E. and Diagnosis
Cytologic or tissue biopsy confirmation is
required to establish a diagnosis of MPE
Diagnostic thoracentesis, if cytology not diagnostic:

M.P.E. and Diagnosis
Cytologic or tissue biopsy confirmation is
required to establish a diagnosis of MPE
Diagnostic thoracentesis, if cytology not diagnostic:

Pleural Biopsy:
Closed-needle pleural biopsy (sensitivity of 40-75%)
Ultrasonography or chest CT-guided percutaneous
pleural biopsy (higher sensitivities and specificities)

Medical thoracoscopy, or
Video Assisted Thoracoscopic Surgery (VATS)
M.P.E. and Diagnosis
Is diagnosis with cytology or histology
always requested (and useful) in our
clinical practice?
M.P.E. and Diagnosis
Does the presence of M.P.E. add
prognostic and therapeutic informations?
M.P.E. and Diagnosis
Non Small Cell Lung Cancer
Does the presence of M.P.E. add
prognostic and therapeutic informations?
M.P.E. and Diagnosis
Non Small Cell Lung Cancer
Poor PS
Known advanced cancer

DIAGNOSIS NOT NECESSARY
M.P.E. and Diagnosis
Non Small Cell Lung Cancer
Poor PS
Known advanced cancer

DIAGNOSIS NOT NECESSARY
Good PS
multimodality treatment

DIAGNOSIS IS CRITICAL
FOR TREATMENT
PLANNING
NSCLC with M.P.E: Prognosis
Patients with M.P.E. (without other metastatic disease) had a
median OS of 8 months
Versus 13 months of other cT4 M0
Versus 6 months of patients with distant metastases
Postmus, JTO 2007
NSCLC with M.P.E: Prognosis
Goldstraw, JTO 2007
TNM staging
Six Edition:

T4
(Stage III B)
TNM staging
Seventh Edition:

M1 a
(Stage IV)
NSCLC with M.P.E: Prognosis
Goldstraw, JTO 2007
TNM staging
Six Edition:

T4
(Stage III B)
TNM staging
Seventh Edition:

M1 a
(Stage IV)
If P.E. is cytologically negative.
and is evaluated as not related to
the tumor by clinical judgment,
patient should be classified as
T1, T2, T3, T4.
Malignant Pleural Effusion
And
Treatment
M.P.E. and Treatment
1) THERAPEUTIC THORACENTESIS



2) PLEURODESIS
M.P.E. and Treatment
Management of MPE is palliative...
1) THERAPEUTIC THORACENTESIS



2) PLEURODESIS
M.P.E. and Treatment
When to proceed with treatment of
Pleural Effusion?
M.P.E. and Treatment
When to proceed with treatment of
Pleural Effusion?
Patient is symptomatic
(for dyspnea or cough or chest pain), and
symptoms are considered to be caused from
pleural effusion.

Patient is not suitable for specific cancer
treatment (eg. chemotherapy), or Pleural
Effusion is resistant to specific cancer treatment.
M.P.E. and Treatment
Is patient symptomatic?
M.P.E. and Treatment
Is patient symptomatic? No intervention
No
M.P.E. and Treatment
Is patient symptomatic? No intervention
Yes
No
Therapeutic Thoracentesis
M.P.E. and Treatment
THERAPEUTIC THORACENTESIS
Symptoms can improve after thoracentesis
But 98% to 100% of patients experience
reaccumulation of fluid and recurrence of
symptoms within 30 days
M.P.E. and Treatment
THERAPEUTIC THORACENTESIS
Symptoms can improve after thoracentesis
But 98% to 100% of patients experience
reaccumulation of fluid and recurrence of
symptoms within 30 days
Repeated
THORACENTESES
PLEURODESIS
M.P.E. and Treatment
THERAPEUTIC THORACENTESIS
Symptoms can improve after thoracentesis
But 98% to 100% of patients experience
reaccumulation of fluid and recurrence of
symptoms within 30 days
Repeated
THORACENTESES
PLEURODESIS
M.P.E. and Treatment
PLEURODESIS
Selection of patients should be based on:.
Patients characteristics




Tumors characteristics
1
2
M.P.E. and Treatment
PLEURODESIS
Selection of patients should be based on:.
Patient characteristics




Tumor characteristics
1
2
Does the patients life
expectancy warrant
pleurodesis? *
(PS has the most value)
* 32% of p. do not survive 30 days after pleurodesis
M.P.E. and Treatment
PLEURODESIS
Selection of patients should be based on:.
Patient characteristics




Tumor characteristics
1
2
Does the patients life
expectancy warrant
pleurodesis? *
(PS has the most value)
* 32% of p. do not survive 30 days after pleurodesis
M.P.E. and Treatment
PLEURODESIS
Pleural Effusion is unlikely to respond to
pleurodesis if:

There is an airway obstruction from an
endobronchial tumor (the lung does not expand
to the chest wall after therapeutic thoracentesis)
Effusion is multiloculated
There are large tumor masses along pleural surfaces
M.P.E. and Treatment
PLEURODESIS
Chest-catheter Pleurodesis
Thoracoscopic Pleurodesis
TALC is considered a superior pleurodesis agent
when compared with other commonly used sclerosant
(as Bleomycin or tetracycline)
Cochrane Review, 2004
M.P.E. and Treatment
Is patient symptomatic? No intervention
Yes
No
Therapeutic Thoracentesis
M.P.E. and Treatment
Is patient symptomatic? No intervention
Yes
No
Therapeutic Thoracentesis
Improvement in symptoms?
M.P.E. and Treatment
Is patient symptomatic? No intervention
Yes
No
Therapeutic Thoracentesis
Improvement in symptoms?
No
M.P.E. and Treatment
Is patient symptomatic? No intervention
Yes
No
Therapeutic Thoracentesis
Improvement in symptoms?
No
Adequate Re-expansion?
Yes
M.P.E. and Treatment
Is patient symptomatic? No intervention
Yes
No
Therapeutic Thoracentesis
Improvement in symptoms?
No
Adequate Re-expansion?
Good PS?
Yes
Yes
M.P.E. and Treatment
Is patient symptomatic? No intervention
Yes
No
Therapeutic Thoracentesis
Improvement in symptoms?
No
Adequate Re-expansion?
Good PS?
Yes
Yes
Pleurodesis
Yes
M.P.E. and Treatment
Is patient symptomatic? No intervention
Yes
No
Therapeutic Thoracentesis
Improvement in symptoms?
No
Adequate Re-expansion?
Good PS?
Yes
Yes
Pleurodesis
No
Yes
M.P.E. and Treatment
Is patient symptomatic? No intervention
Yes
No
Therapeutic Thoracentesis
Improvement in symptoms?
No
Adequate Re-expansion?
Good PS?
Yes
Yes
Pleurodesis
No
No
Yes
M.P.E. and Treatment
Is patient symptomatic? No intervention
Yes
No
Therapeutic Thoracentesis
Improvement in symptoms?
No
Adequate Re-expansion?
Good PS?
Yes
Yes
Repeated Thoracentesis
Pleural Catheter
Pleurodesis
No
No
Yes
M.P.E. and Treatment
Repeated
THORACENTESES
Should be reserved for patients who:

(1) Appear unlikely to survive beyond 1 to 3 months
(2) Cannot tolerate other more interventional
procedures to control pleural fluid, such as pleurodesis.
(3) Have a PE that does not respond to pleurodesis



M.P.E. and Treatment
Repeated
THORACENTESES
Should be reserved for patients who:

(1) Appear unlikely to survive beyond 1 to 3 months
(2) Cannot tolerate other more interventional
procedures to control pleural fluid, such as pleurodesis.
(3) Have a PE that does not respond to pleurodesis


(4) Have cancers that commonly respond to therapy
with resolution of the associated effusions


...OR...
M.P.E. and Treatment
Is patient symptomatic? No intervention
Yes
No
Therapeutic Thoracentesis
Improvement in symptoms?
No
Adequate Re-expansion?
Good PS?
Yes
Yes
Repeated Thoracentesis
Pleural Catheter
Pleurodesis
No
No
Yes
M.P.E. and Treatment
Is patient symptomatic? No intervention
Yes
No
Therapeutic Thoracentesis
Is tumor likely
to respond to
chemotherapy?
Improvement in symptoms?
No
Adequate Re-expansion?
Good PS?
Yes
Yes
Repeated Thoracentesis
Pleural Catheter
Pleurodesis
No
No
Yes
SCLC
M.P.E. and Treatment
Is tumor likely
to respond to
chemotherapy
?

SCLC is an aggressive disease associated with early
loco-regional and distant metastases Extensive Stage (ED-
SCLC) is present at diagnosis in more than 60%70% of cases
[median OS of 9 months]

Highly sensitive to both chemotherapy and RT
Platinum/Etoposide regimens are usually associated with a rapid
objective response in 50% to 80% of patients with ED-SCLC

Patients who not respond to initial chemotherapy (Refractory
disease) have a worse prognosis, with an expected median survival
of 2-3 months
SCLC
M.P.E. and Treatment
Is tumor likely
to respond to
chemotherapy
?

SCLC is an aggressive disease associated with early
loco-regional and distant metastases Extensive Stage (ED-
SCLC) is present at diagnosis in more than 60%70% of cases
[median OS of 9 months]

Highly sensitive to both chemotherapy and RT
Platino/Etoposide regimens are usually associated with a rapid
objective response in 50% to 80% of patients with ED-SCLC

Patients who not respond to initial chemotherapy (Refractory
disease) have a worse prognosis, with an expected median survival
of 2-3 months
SCLC patients can occasionally be palliated with only 1 thoracentesis
M.P.E. and Treatment
SCLC
About 30% of SCLC patients present with Limited Stage disease
8090% of these respond to combination chemotherapy, with or
without thoracic radiation, and 40%70% achieve complete
remission.
[median OS of 1220 months, 5-year survival of 510%]

LD-SCLC with ipsilateral pleural effusion accounted for 9% of all
the patients with SCLC and 17% of all the patients with LD SCLC
M.P.E. and Treatment
SCLC
About 30% of SCLC patients present with Limited Stage disease
8090% of these respond to combination chemotherapy, with or
without thoracic radiation, and 40%70% achieve complete
remission.
[median OS of 1220 months, 5-year survival of 510%]

LD-SCLC with ipsilateral pleural effusion accounted for 9% of all
the patients with SCLC and 17% of all the patients with LD SCLC
Which
Treatment?
Which
Staging?
M.P.E. and Treatment
SCLC
LD-SCLC with pleural effusion... Which staging?
1989, IALSC classification
LIMITED STAGE:
disease confined to the
ipsilateral hemithorax, which
can be encompassed within a
tolerable radiation field
Loco-regional extension
Ipsilateral supraclavicular
nodes
LIMITED STAGE:
Ipsilateral and controlateral
hilar nodes
Ipsilateral and controlateral
mediastinal nodes
Ipsilateral and controlateral
supraclavicular nodes
Ipsilateral pleural effusion
regardless of the cytology

M.P.E. and Treatment
SCLC
1957, VALG classification
LD-SCLC with pleural effusion... Which staging?
Retrospective study
to compare the prognostic impact of the two staging systems
(VALG vs IASLC)
e.g. Pleural effusion
Micke,2002
M.P.E. and Treatment
SCLC
LD-SCLC with pleural effusion... Which staging?
LD-SCLC with pleural effusion... Which staging?
SCLC
The revised UICC/AJCC staging system:
The survival of patients with LD with
effusion is intermediate between
those of patients with LD without
effusion and patients with ED.
(p value 0.0001)


Result of cytologic examination of
PE (available for only 68 patients):
The survival of patients with LD
with effusion, whether cytologically
negative or positive, remained
intermediate Shepherd, 2007
M.P.E. and Treatment
M.P.E. and Treatment
SCLC
LD-SCLC with pleural effusion... Which treatment?

The indication for definitive TRT in patients
with LD-SCLC and ipsilateral pleural effusion
have not been thoroughly investigated

Definitive TRT is contraindicated in patients
with malignant pleural effusion
M.P.E. and Treatment
SCLC
LD-SCLC with pleural effusion... Which treatment?
M.P.E. and Treatment
SCLC
LD-SCLC with pleural effusion... Which treatment?
26 pz:
CT + TRT

8 pz:
Did not receive
TRT in spite of
the disappearance
of pleural effusion
after I-line CT
28 pz:
Did not receive
TRT, and pleural
effusion persisted
after I-line CT
3: TRT concurrently
with I course
10: TRT concurrently
with II or III or
IV course
13: TRT sequentially

Niho, J Thorac Oncol 2008
M.P.E. and Treatment
SCLC
62 LD-SCLC with ipsilateral pleural effusion
(citologically negative and positive)
Retrospective
study
Pleural effusion and Treatment
Niho, J Thorac Oncol 2008
SCLC

long-term survival was achieved by LD-SCLC patients who underwent definitive
TRT after their ipsilateral pleural effusion disappeared after induction CT.

62 LD-SCLC with ipsilateral pleural effusion
(citologically negative and positive)
Retrospective
study
M.P.E. and Treatment
Is patient symptomatic? No intervention
Yes
No
Therapeutic Thoracentesis
Is tumor likely
to respond to
chemotherapy?
Improvement in symptoms?
No
Adequate Re-expansion?
Good PS?
Yes
Yes
Repeated Thoracentesis
Pleural Catheter
Pleurodesis
No
No
Yes
0%
0%
0%
0%
0%
Which rate of patients with Malignant Pleural
Effusion (MPE) experiences reaccumulation of
fluid within 30 days after thoracentesis?
0 / 0
Cross-tab label

1. 30-40%
2. 80-90%
3. 95-100%
4. 10-20%
5. 0%

In which cases should pleurodesis be
considered as a valid therapeutic option?
1. Adeguate PS and patients life
expectancy (eg longer than 3
months)
2. Patients dyspnea improved after
therapeutic thoracentesis
3. The underlying tumor and
resulting Malignant Pleural
Effusion are not responsive to
chemotherapy or radiotherapy
4. All the answers above
5. None of the answers above

0 / 0
Cross-tab label
1
20%
2
20%
3
20%
4
20%
5
20%

The presence of Malignant Pleural Effusion is
required to stage a NSCLC as :
1. Stage III B
2. Stage III A
3. Stage IV
4. It is not arleady
established
5. Malignant Pleural Effusion
is not considered for
staging

0 / 0
Cross-tab label
20% 20% 20% 20% 20%
1 2 3 4 5