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8/11/2019 B_Enrico Cortesi_Management of malignant pleural effusions-1.ppt
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Rome, May 15-16, 2009
Enrico Cortesi, Martina PuglisiSapienza, Universit di Roma
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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%
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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 thoracentesis3. The underlying tumor and
resulting Malignant Pleural
Effusion are not responsive to
chemotherapy or radiotherapy4. 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%
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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 Effusionis not considered for
staging
29 / 30 Cross-tab label
0% 0%
97%
3% 0%
1 2 3 4 5
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Malignant Pleural Effusion (M.P.E.)
An M.P.E. is defined by the presenceof cancer cellsin the pleural space
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Malignant Pleural Effusion (M.P.E.)
An M.P.E. is defined by the presenceof cancer cellsin the pleural space
Underlying Primary Cancer1.Lung tumors (including malignant pleural
mesothelioma) NSCLC:14% at the time of
diagnosis, 50% with advanced disease2.Breast cancer
3.Ovarian cancer, gastric cancer
4. Hodgkins and non-Hodgkins lymphoma
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Malignant Pleural Effusion (M.P.E.)
An M.P.E. is defined by the presenceof cancer cellsin the pleural space
Cancer cells reach thevisceral pleura(throughthe pulmonary
vasculature)or theparietal 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)
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Malignant Pleural Effusion (M.P.E.)
Paramalignant Effusion
1.Mediastinal lymph node tumor infiltration2. Bronchial obstruction/Atelectasis
3. Pulmonary embolism
4.Superior vena cava syndrome
5. Decreased oncotic pressure (cachexia)
6. Radiotherapy/Chemotherapy
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Malignant Plural EffusionAndDiagnosis
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M.P.E. and Diagnosis
Cytologicor tissue biopsyconfirmation isrequired to establish a diagnosis of MPE
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M.P.E. and Diagnosis
Cytologicor tissue biopsyconfirmation isrequired to establish a diagnosis of MPE
Diagnostic thoracentesis:Diagnostic yield ofPF cytologyranging 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 standardcytology: Electrochetoluminescence fortumor markers,
genetic analysis
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M.P.E. and Diagnosis
Cytologicor tissue biopsyconfirmation isrequired to establish a diagnosis of MPE
Diagnostic thoracentesis, if cytology not diagnostic:
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M.P.E. and Diagnosis
Cytologicor tissue biopsyconfirmation isrequired 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, orVideo Assisted Thoracoscopic Surgery (VATS)
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M.P.E. and Diagnosis
Is diagnosis with cytologyor histology
always requested (and useful) in our
clinical practice?
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M.P.E. and Diagnosis
Does the presence of M.P.E. addprognosticand therapeuticinformations?
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M.P.E. and Diagnosis
Non Small Cell Lung Cancer
Does the presence of M.P.E. addprognosticand therapeuticinformations?
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M.P.E. and Diagnosis
Non Small Cell Lung Cancer
Poor PSKnown advanced cancer
DIAGNOSIS NOT NECESSARY
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M.P.E. and Diagnosis
Non Small Cell Lung Cancer
Poor PSKnown advanced cancer
DIAGNOSIS NOT NECESSARY
Good PSmultimodality treatment
DIAGNOSIS IS CRITICAL
FOR TREATMENTPLANNING
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NSCLC with M.P.E:PrognosisPatients with M.P.E. (without other metastatic disease) had a
median OS of 8 months Versus 13 monthsof other cT4 M0Versus 6 monthsof patients with distant metastases
Postmus, JTO 2007
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NSCLC with M.P.E:Prognosis
Goldstraw, JTO 2007
TNM stagingSix Edition:
T4(Stage III B)
TNM stagingSeventh Edition:
M1 a(Stage IV)
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NSCLC with M.P.E:Prognosis
Goldstraw, JTO 2007
TNM stagingSix Edition:
T4(Stage III B)
TNM stagingSeventh Edition:
M1 a(Stage IV)If P.E. is cytologically negative.
and is evaluated as not related tothe tumor by clinical judgment,patient should be classified as
T1, T2, T3, T4.
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Malignant Pleural EffusionAndTreatment
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M.P.E. and Treatment
1)THERAPEUTIC THORACENTESIS
2)PLEURODESIS
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M.P.E. and Treatment
Management of MPE is palliative...
1)THERAPEUTIC THORACENTESIS
2)PLEURODESIS
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M.P.E. and Treatment
When to proceed with treatment ofPleural Effusion?
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M.P.E. and Treatment
When to proceed with treatment ofPleural Effusion?
Patient is symptomatic
(for dyspnea or cough or chest pain), andsymptoms are considered to be caused frompleural effusion.
Patient is not suitable forspecific cancertreatment (eg. chemotherapy), or PleuralEffusion is resistant to specific cancer treatment.
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M.P.E. and Treatment
Is patient symptomatic?
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M.P.E. and Treatment
Is patient symptomatic? No interventionNo
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M.P.E. and Treatment
Is patient symptomatic? No intervention
Yes
No
Therapeutic Thoracentesis
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M.P.E. and Treatment
THERAPEUTIC THORACENTESIS
Symptoms can improve after thoracentesis
But 98% to 100%of patients experience
reaccumulation of fluidand recurrence of
symptomswithin 30 days
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M.P.E. and Treatment
THERAPEUTIC THORACENTESIS
Symptoms can improve after thoracentesis
But 98% to 100%of patients experience
reaccumulation of fluidand recurrence of
symptomswithin 30 days
RepeatedTHORACENTESES
PLEURODESIS
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M.P.E. and Treatment
THERAPEUTIC THORACENTESIS
Symptoms can improve after thoracentesis
But 98% to 100%of patients experience
reaccumulation of fluidand recurrence of
symptomswithin 30 days
RepeatedTHORACENTESES
PLEURODESIS
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M.P.E. and Treatment
PLEURODESIS
Selection of patients should be based on:.
Patients characteristics
Tumors characteristics
1
2
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M.P.E. and Treatment
PLEURODESIS
Selection of patients should be based on:.
Patient characteristics
Tumor characteristics
1
2
Does the patients lifeexpectancy warrantpleurodesis? *
(PShas the most value)
*
32% of p. do not survive 30 days after pleurodesis
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M.P.E. and Treatment
PLEURODESIS
Selection of patients should be based on:.
Patient characteristics
Tumor characteristics
1
2
Does the patients lifeexpectancy warrantpleurodesis? *
(PShas the most value)
*
32% of p. do not survive 30 days after pleurodesis
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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
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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
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M.P.E. and Treatment
Is patient symptomatic? No intervention
Yes
No
Therapeutic Thoracentesis
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M.P.E. and Treatment
Is patient symptomatic? No intervention
Yes
No
Therapeutic Thoracentesis
Improvement in symptoms?
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M.P.E. and Treatment
Is patient symptomatic? No intervention
Yes
No
Therapeutic Thoracentesis
Improvement in symptoms?No
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M.P.E. and Treatment
Is patient symptomatic? No intervention
Yes
No
Therapeutic Thoracentesis
Improvement in symptoms?No
Adequate Re-expansion?
Yes
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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
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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
PleurodesisYes
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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
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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
NoYes
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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
NoYes
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M.P.E. and Treatment
RepeatedTHORACENTESES
Should be reserved for patients who:
(1)Appear unlikely to survive beyond 1 to 3 months(2)Cannot tolerateother more interventional
procedures to control pleural fluid, such as pleurodesis.(3)Have a PE that does not respondto pleurodesis
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M.P.E. and Treatment
RepeatedTHORACENTESES
Should be reserved for patients who:
(1)Appear unlikely to survive beyond 1 to 3 months(2)Cannot tolerateother more interventional
procedures to control pleural fluid, such as pleurodesis.(3)Have a PE that does not respondto pleurodesis
(4)Have cancers that commonly respond to therapywith resolution of the associated effusions
...OR...
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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
NoYes
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M.P.E. and Treatment
Is patient symptomatic? No intervention
Yes
No
Therapeutic Thoracentesis
Is tumor likelyto respond to
chemotherapy?
Improvement in symptoms?No
Adequate Re-expansion?
Good PS?
Yes
Yes
Repeated Thoracentesis
Pleural Catheter
Pleurodesis
No
NoYes
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SCLC
M.P.E. and TreatmentIs tumor likelyto respond tochemotherapy
?
SCLC is an aggressive disease associated with earlyloco-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 RTPlatinum/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 (Refractorydisease) have a worse prognosis, with an expected median survivalof 2-3 months
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SCLC
M.P.E. and TreatmentIs tumor likelyto respond tochemotherapy
?
SCLC is an aggressive disease associated with earlyloco-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 RTPlatino/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 (Refractorydisease) have a worse prognosis, with an expected median survivalof 2-3 months
SCLC patients can occasionally be palliated with only 1 thoracentesis
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M.P.E. and Treatment
SCLC
About 30% of SCLC patients present with Limited Stagedisease8090% of these respond to combination chemotherapy, with or
without thoracic radiation, and 40%70% achieve completeremission.[median OS of 1220 months, 5-year survival of 510%]
LD-SCLCwith ipsilateral pleuraleffusionaccounted for 9%of all
the patients with SCLC and 17%of all the patients with LD SCLC
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M.P.E. and Treatment
SCLC
About 30% of SCLC patients present with Limited Stagedisease8090% of these respond to combination chemotherapy, with or
without thoracic radiation, and 40%70% achieve completeremission.[median OS of 1220 months, 5-year survival of 510%]
LD-SCLCwith ipsilateral pleuraleffusionaccounted for 9%of all
the patients with SCLC and 17%of all the patients with LD SCLC
WhichTreatment?
WhichStaging?
E
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M.P.E. and Treatment
SCLCLD-SCLC with pleural effusion... Which staging?
P E d
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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 controlateralhilar nodes
Ipsilateral and controlateralmediastinal nodes
Ipsilateral and controlateralsupraclavicular nodes
Ipsilateral pleural effusion
regardless of the cytology
M.P.E. and Treatment
SCLC
1957, VALG classification
LD-SCLC with pleural effusion... Which staging?
M P E d T
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Retrospective studyto compare the prognostic impact of the two staging systems
(VALG vs IASLC)
e.g. Pleural effusion
Micke,2002
M.P.E. and Treatment
SCLCLD-SCLC with pleural effusion... Which staging?
M P E d T
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LD-SCLC with pleural effusion... Which staging?SCLC
The revised UICC/AJCC staging system:
The survival of patients with LD witheffusionis intermediate betweenthose of patients with LD withouteffusionand patients with ED.
(p value 0.0001)
Result of cytologic examinationofPE (available for only 68 patients):The survival of patients with LDwith effusion, whether cytologicallynegative or positive, remained
intermediate Shepherd, 2007
M.P.E. and Treatment
M P E d T
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M.P.E. and Treatment
SCLCLD-SCLC with pleural effusion... Which treatment?
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M P E d T t t
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M.P.E. and Treatment
SCLCLD-SCLC with pleural effusion... Which treatment?
M P E d T t t
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26 pz:
CT + TRT
8 pz:Did not receiveTRT in spite of
the disappearanceof pleural effusion
after I-line CT
28 pz:Did not receiveTRT, and pleural
effusionpersistedafter I-line CT
3: TRT concurrentlywith I course10:TRT concurrently
with II or III orIV course
13:TRT sequentiallyNiho, J Thorac Oncol 2008
M.P.E. and Treatment
SCLC62LD-SCLC with ipsilateral pleural effusion
(citologically negative and positive)
Retrospectivestudy
Pl l ff i d T t t
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Pleural effusionandTreatment
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.
62LD-SCLC with ipsilateral pleural effusion(citologically negative and positive)
Retrospectivestudy
M P E d T t t
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M.P.E. and Treatment
Is patient symptomatic? No intervention
Yes
No
Therapeutic Thoracentesis
Is tumor likelyto respond to
chemotherapy?
Improvement in symptoms?No
Adequate Re-expansion?
Good PS?
Yes
Yes
Repeated Thoracentesis
Pleural Catheter
Pleurodesis
No
NoYes
Which rate of patients with Malignant Pleural
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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
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In which cases should pleurodesis be
considered as a valid therapeutic option?
1. Adeguate PS and patients lifeexpectancy (eg longer than 3
months)
2. Patients dyspnea improved after
therapeutic thoracentesis3. 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%
Th f M li t Pl l Eff i i
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The presence of Malignant Pleural Effusion is
required to stage a NSCLC as :
1. Stage III B
2. Stage III A
3. Stage IV4. It is not arleady
established
5. Malignant Pleural Effusion
is not considered for
staging
20% 20% 20% 20% 20%
1 2 3 4 5